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Sample records for cell transfusion independence

  1. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    OpenAIRE

    Leitch, Heather A.; Vickars, Linda M.; Chase, Jocelyn M.; Badawi, Maha A.

    2010-01-01

    Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC). A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the ...

  2. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  3. Transfusion of platelets, but not of red blood cells, is independently associated with nosocomial infections in the critically ill

    NARCIS (Netherlands)

    Engele, Leo J.; Straat, Marleen; van Rooijen, Ingeborg H M; de Vooght, Karen M K; Cremer, Olaf L.; Schultz, Marcus J.; Bos, Lieuwe D J; Juffermans, Nicole P.

    2016-01-01

    Background: Red blood cell (RBC) transfusion has been associated with nosocomial infection in the critically ill patients. However, this association may be confounded by length of stay, as prolonged intensive care unit (ICU stay) increases both risk of infection and risk of transfusion. Also, it is

  4. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai;

    2015-01-01

    OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions. DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: Cochrane central register of controlled...... trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials....... TRIAL SELECTION: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size. DATA EXTRACTION: Two authors independently screened...

  5. Red blood cell transfusion in septic shock

    DEFF Research Database (Denmark)

    Rosland, Ragnhild G; Hagen, Marte U; Haase, Nicolai;

    2014-01-01

    BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients. METHODS: We did a prospective cohort study at 7...... general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3 (interquartile range 2-5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4-8.9) g....../dl and independent of shock day and bleeding. Patients with cardiovascular disease were transfused at higher haemoglobin levels. Transfused patients had higher Simplified Acute Physiology Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes, lower haemoglobin levels days 1 to 5, higher...

  6. Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

    OpenAIRE

    Harpreet Kochhar; Chantal S. Leger; Leitch, Heather A.

    2015-01-01

    Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of ...

  7. Red blood cell transfusion during septic shock in the ICU

    DEFF Research Database (Denmark)

    Perner, A; Smith, S H; Carlsen, S;

    2012-01-01

    Transfusion of red blood cells (RBCs) remains controversial in patients with septic shock, but current practice is unknown. Our aim was to evaluate RBC transfusion practice in septic shock in the intensive care unit (ICU), and patient characteristics and outcome associated with RBC transfusion....

  8. Transfusion of leukocyte-depleted red blood cells is not a risk factor for nosocomial infections in critically ill children

    NARCIS (Netherlands)

    van der Wal, Judith; van Heerde, Marc; Markhorst, Dick G.; Kneyber, Martin C. J.

    2011-01-01

    Objectives: Transfusion of red blood cells is increasingly linked with adverse outcomes in critically ill children. We tested the hypothesis that leukocyte-depleted red blood cell transfusions were independently associated with increased development of bloodstream infections, ventilator-associated p

  9. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai;

    2015-01-01

    titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean...

  10. Case reports: delayed hemolytic transfusion reaction in sickle cell disease.

    Science.gov (United States)

    Syed, S K; Sears, D A; Werch, J B; Udden, M M; Milam, J D

    1996-10-01

    This article reports the details of delayed hemolytic transfusion reactions in four patients with sickle cell disease. These cases demonstrate the characteristics of the reactions, the significant risks involved, and the principles useful in diagnosis and treatment. Patients with sickle cell disease are at particular risk for delayed hemolytic transfusion reactions because they may be transfused at intervals over many years; they frequently form alloantibodies because of antigenic differences from the donor population; and they may receive emergency care in different hospitals where transfusion records are not available. In addition, exchange transfusions, which are often used for patients with sickle cell disease and which were given in three of these cases, raise the risks through increased exposure to foreign erythrocyte antigens and through an increased volume of erythrocytes susceptible to hemolysis. It was concluded that the hazards of these transfusion reactions justify preventive measures, such as extended erythrocyte phenotyping of patients with sickle cell disease and extended phenotypic matching of transfused cells. PMID:8853066

  11. Transfusion of Leukocyte-Depleted RBCs Is Independently Associated With Increased Morbidity After Pediatric Cardiac Surgery

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; Grotenhuis, Femke; Berger, Rolf F. M.; Ebels, Tjark W.; Burgerhof, Johannes G. M.; Albers, Marcel J. I. J.

    2013-01-01

    Objective: To test the hypothesis that transfusion of leukocyte-depleted RBC preparations within the first 48 hours of PICU stay was independently associated with prolonged duration of mechanical ventilation, irrespective of surgery type and disease severity. Design: Retrospective, observational stu

  12. Transfusion management of patients with red blood cell antibodies

    OpenAIRE

    Bujandrić Nevenka B.; Grujić Jasmina N.; Krga-Milanović Mirjana M.

    2013-01-01

    Introduction. Red blood cell antibodies may cause a positive result of pre-transfusion blood compatibility testing (crossmatch test). It can be a problem to provide suitable blood units for patients with clinically significant antibodies to high-frequency antigens as well as for those with multiple alloantibody specificities. This study was aimed at identifying transfused patients in the population of South-Backa who had developed clinically significant red...

  13. Red blood cell transfusion in preterm neonates: current perspectives

    Directory of Open Access Journals (Sweden)

    Chirico G

    2014-06-01

    Full Text Available Gaetano ChiricoNeonatology and Neonatal Intensive Care Unit, Children Hospital, Spedali Civili, Brescia, ItalyAbstract: Preterm neonates, especially very low birth weight infants, remain a category of patients with high transfusion needs; about 90% of those with <1,000 g birth weight may be transfused several times during their hospital stay. However, neonatal red blood cells (RBC transfusion is not without risks. In addition to well-known adverse events, several severe side effects have been observed unique to preterm infants, such as transfusion-related acute gut injury, intraventricular hemorrhage, and increased mortality risk. It is therefore important to reduce the frequency of RBC transfusion in critically ill neonates, by delayed clamping or milking the umbilical cord, using residual cord blood for initial laboratory investigations, reducing phlebotomy losses, determining transfusion guidelines, and ensuring the most appropriate nutrition, with the optimal supplementation of iron, folic acid, and vitamins. Ideally, RBC transfusion should be tailored to the individual requirements of the single infant. However, many controversies still remain, and the decision on whether to transfuse or not is often made on an empirical basis. Recently, a few clinical trials have been performed with the aim to compare the risk/benefit ratio of restrictive versus liberal transfusion criteria. No significant differences in short-term outcomes were observed, suggesting that the restrictive criteria may reduce the need for transfusion and the related side effects. Neurodevelopmental long-term outcome seemed more favorable in the liberal group at first evaluation, especially for boys, and significantly better in the restrictive group at a later clinical investigation. Magnetic resonance imaging scans, performed at an average age of 12 years, showed that intracranial volume was substantially smaller in the liberal group compared with controls. When sex effects

  14. Perioperative Red Blood Cell Transfusion: What We Do Not Know

    Institute of Scientific and Technical Information of China (English)

    Chong Lei; Li-Ze Xiong

    2015-01-01

    Objective:Blood transfusion saves lives but may also increase the risk of injury.The objective of this review was to evaluate the possible adverse effects related to transfusion of red blood cell (RBC) concentrates stored for prolonged periods.Data Sources:The data used in this review were mainly from PubMed articles published in English up to February 2015.Study Selection:Clinical and basic research articles were selected according to their relevance to this topic.Results:The ex vivo changes to RBC that occur during storage are collectively called storage lesion.It is still inconclusive if transfusion of RBC with storage lesion has clinical relevance.Multiple ongoing prospective randomized controlled trials are aimed to clarify this clinical issue.It was observed that the adverse events related to stored RBC transfusion were prominent in certain patient populations,including trauma,critical care,pediatric,and cardiac surgery patients,which leads to the investigation of underlying mechanisms.It is demonstrated that free hemoglobin toxicity,decreasing of nitric oxide bioavailability,and free iron-induced increasing of inflammation may play an important role in this process.Conclusion:It is still unclear whether transfusion of older RBC has adverse effects,and if so,which factors determine such clinical effects.However,considering the magnitude of transfusion and the widespread medical significance,potential preventive strategies should be considered,especially for the susceptible recipients.

  15. Best practices for transfusion for patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Ted Wun

    2010-01-01

    Full Text Available The beta-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research.  A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

  16. A delayed hemolytic transfusion reaction after partial exchange transfusion for sickle cell disease in pregnancy: a case report and review of the literature.

    Science.gov (United States)

    Brumfield, C G; Huddleston, J F; DuBois, L B; Harris, B A

    1984-03-01

    A delayed hemolytic transfusion reaction that occurred after a prophylactic partial exchange transfusion for sickle-cell disease in pregnancy is described. The clinical presentation and laboratory findings of delayed transfusion reactions are discussed, with special emphasis on problems associated in the sickle-cell disease patient. Suggestions on how to minimize the risk of transfusion reactions in the pregnant sickle-cell disease patient are given. PMID:6700873

  17. A selective tropism of transfused oval cells for liver

    Institute of Scientific and Technical Information of China (English)

    Jian-Zhi Chen; Hai Hong; Jin Xiang; Ling Xue; Guo-Qiang Zhao

    2003-01-01

    AIM: To explore the biological behaviors of hepatic oval cells after transfused into the circulation of experimental animals.METHODS: Oval cells from male SD rat were transfused into the circulation of a female rat which were treated by a 2-AAF/CCl4 program, through caudal vein. Sex-determining gene sry which located on Y chromosome was examined by PCR and in situ hybridization technique in liver, kidney and spleen of the experimental animals, respectively.RESULTS: The results of the cell-transplant experiment showed that the srygene was detectable only in the liver but not in spleen and kidney of the experimental rats, and no signals could be detected in the control animals. It can be also morphologically proved that some exogenous cells had migrated into the parenchyma of the liver and settled there.CONCLUSION: The result means that there are exogenous cells located in the liver of the experimental animal and the localization is specific to the liver. This indicates that some "signal molecules" must exist in the circulation of the rats treated by 2-AAF/CCl4. These "signal molecules" might play an important role in specific localization and differentiation of transfused oval cells.

  18. Challenges and promises for the development of donor-independent platelet transfusions.

    Science.gov (United States)

    Lambert, Michele P; Sullivan, Spencer K; Fuentes, Rudy; French, Deborah L; Poncz, Mortimer

    2013-04-25

    Platelet transfusions are often a life-saving intervention, and the use of platelet transfusions has been increasing. Donor-derived platelet availability can be challenging. Compounding this concern are additional limitations of donor-derived platelets, including variability in product unit quality and quantity, limited shelf life and the risks of product bacterial contamination, other transfusion-transmitted infections, and immunologic reactions. Because of these issues, there has been an effort to develop strategies to generate platelets from exogenously generated precursor cells. If successful, such platelets have the potential to be a safer, more consistent platelet product, while reducing the necessity for human donations. Moreover, ex vivo-generated autologous platelets or precursors may be beneficial for patients who are refractory to allogeneic platelets. For patients with inherited platelet disorders, ex vivo-generated platelets offer the promise of a treatment via the generation of autologous gene-corrected platelets. Theoretically, ex vivo-generated platelets also offer targeted delivery of ectopic proteins to sites of vascular injury. This review summarizes the current, state-of-the-art methodologies in delivering a clinically relevant ex vivo-derived platelet product, and it discusses significant challenges that must be overcome for this approach to become a clinical reality.

  19. Transfusion management of patients with red blood cell antibodies

    Directory of Open Access Journals (Sweden)

    Bujandrić Nevenka B.

    2013-01-01

    Full Text Available Introduction. Red blood cell antibodies may cause a positive result of pre-transfusion blood compatibility testing (crossmatch test. It can be a problem to provide suitable blood units for patients with clinically significant antibodies to high-frequency antigens as well as for those with multiple alloantibody specificities. This study was aimed at identifying transfused patients in the population of South-Backa who had developed clinically significant red blood cell alloantibodies. Material and methods. We analyzed the records of crossmatch results and antibody screening performed at the Blood Transfusion Institute of Vojvodina during 2012. Results. Antibodies were found in 103 patients: A 63 patients with single antibodies: 1 16 with antibodies of unknown specificity (3 autoantibodies, 13 alloantibodies; 2 39 with clinically significant antibodies (23 from Rh system (2 anti-C, 2 anti-D, 12 anti-E, 7 anti-c, 4 anti-K, 3 anti-Fya, 7 anti-Jka, 2 anti-S; 3 8 with usually not significant antibodies (6 anti-M, 1 anti-A1, 1 anti- Cw; B 40 patients developed multiple antibodies: 1 all patients had at least one clinically significant antibody from various blood group system (44 Rh, 13 Kell, 7 Kidd, 7 MNSs (S, s; 2 3 patients had usually not significant antibodies (1 Lewis, 2 Lutheran; 3 3 patients occasionally had clinically significant antibody (3 anti- Yta; 4 3 patients had antibodies of unknown specificity (2 autoantibodies, 1alloantibody. Antibodies detected in the majority of patients (65-63.1% had a specificity of Rh and/or the Kell system. Conclusions. The main goal of pre-transfusion blood compatibility testing is to detect clinically significant antibodies. The provision of antigen negative blood units for those patients is a special challenge for blood establishments. Database with a sufficient number of typed blood donors can help to resolve this problem.

  20. Successful implementation of a packed red blood cell and fresh frozen plasma transfusion protocol in the surgical intensive care unit.

    Directory of Open Access Journals (Sweden)

    Benjamin E Szpila

    Full Text Available Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC and fresh frozen plasma (FFP transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU.We performed a retrospective, historical control analysis comparing before (PRE and after (POST implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received.829 total patients were included in the analysis (PRE, n=372; POST, n=457. Despite higher mean age (56 vs. 52 years, p=0.01 and APACHE II scores (12.5 vs. 11.2, p=0.006, mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03 and fresh frozen plasma (0.3 vs. 1.2, p=0.007 in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39. There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80 in the POST cohort after controlling for age, illness severity and amount of blood products transfused.Implementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.

  1. Phase I/II safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.

    LENUS (Irish Health Repository)

    Cahill, M R

    2010-08-01

    Variant Creutzfeldt-Jakob (vCJD) is a fatal transfusion transmissible prion infection. No test for vCJD in the donor population is currently available. Therefore, prion removal by filtration of red cell concentrate (RCC) is an attractive option for prevention.

  2. A case of delayed hemolytic transfusion reaction in sickle cell disease patient

    Science.gov (United States)

    Dogra, Ashu; Sidhu, Meena

    2016-01-01

    Sickle cell disease (SCD) is autosomal recessive, genetically transmitted hemoglobinopathy responsible for considerable morbidity and mortality. It is prevalent in many parts of India including Central India, where the prevalence in different communities has ranged from 9.4% to 22%. Perioperative management may include transfusion of red blood cells. Hemolytic transfusion reactions can occur, and these can be either acute or delayed. We present a case of delayed hemolytic transfusion reaction in a patient with SCD. PMID:27605854

  3. The effects of non-leukoreduced red blood cell transfusions on microcirculation in mixed surgical patients.

    NARCIS (Netherlands)

    Ayhan, B.; Yuruk, K.; Koene, S.; Sahin, A.; Ince, C.; Aypar, U.

    2013-01-01

    BACKGROUND: The impact of the storage process on oxygen-carrying properties of red blood cells and the efficacy of red blood cell (RBC) transfusions concerning tissue oxygenation remain an issue of debate in transfusion medicine. Storage time and leukocyte content probably interact since longer stor

  4. Preoperative factors associated with red blood cell transfusion in hip fracture patients

    DEFF Research Database (Denmark)

    Madsen, Christian Medom; Jørgensen, Henrik Løvendahl; Norgaard, Astrid;

    2014-01-01

    Red blood cell (RBC) transfusion is a frequently used treatment in patients admitted with a fractured hip, but the use remains an area of much debate. The aim of this study was to determine preoperative factors associated with the risk of receiving a red blood cell transfusion in hip fracture...

  5. Adverse effects to transfusion with red donor blood cells are frequent

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Nørgaard, Astrid; Burcharth, Jakob;

    2014-01-01

    Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating...... conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment....

  6. Outpatient red blood cell transfusion payments among patients on chronic dialysis

    Directory of Open Access Journals (Sweden)

    Gitlin Matthew

    2012-11-01

    Full Text Available Abstract Background Payments for red blood cell (RBC transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. Methods Using Truven Health MarketScan® data (1/1/02-10/31/10 in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days, blood acquisition/administration (within 2 days, and associated complications (within 3 days for acute events; up to 45 days for chronic events. Results A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD] age was 60.9 (15.0 years, and mean Charlson comorbidity index was 4.3 (2.5. During a mean (SD follow-up of 495 (474 days, patients had a mean of 2.2 (3.8 outpatient RBC transfusion episodes. Mean/median (SD total payment per RBC transfusion episode was $854/$427 ($2,060 with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD $213 ($168 for delayed hemolytic transfusion reaction to $19,466 ($15,424 for congestive heart failure. Conclusions Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.

  7. A case of transfusion independence in a patient with myelodysplastic syndrome using deferasirox, sustained for two years after stopping therapy

    OpenAIRE

    Sanford, D.; Hsia, C C

    2015-01-01

    Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.

  8. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery

    DEFF Research Database (Denmark)

    Jensen, L S; Andersen, A J; Christiansen, P M;

    1992-01-01

    The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measure...

  9. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease

    Science.gov (United States)

    Desai, Payal C.; Deal, Allison M.; Pfaff, Emily R.; Qaqish, Bahjat; Hebden, Leyna M.; Park, Yara A.; Ataga, Kenneth I.

    2016-01-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14–27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71–7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66–35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. PMID:25963831

  10. Transfusion Practices in the Management of Sickle Cell Disease: A Survey of Florida Hematologists/Oncologists

    OpenAIRE

    Dunbar, Levette N.; LaRae Coleman Brown; Rivera, Donna R.; Hartzema, Abraham G.; Richard Lottenberg

    2012-01-01

    The purpose of this study was to characterize transfusion practices in the management of sickle cell disease and to identify factors attributing to differences in prescribing practices among Florida hematologists/oncologists. A cross-sectional study was performed in 2005-2006 utilizing a mail survey. The survey instrument addressed practice characteristics, sickle cell patient populations, transfusion settings, indications and techniques, red blood cell phenotype specifications/modifications,...

  11. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn;

    2013-01-01

    BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS: The Transfusion...... Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin...... and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed...

  12. Intra-operative intravenous fluid restriction reduces perioperative red blood cell transfusion in elective cardiac surgery, especially in transfusion-prone patients: a prospective, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Georgopoulou Stavroula

    2010-02-01

    Full Text Available Abstract Background Cardiac surgery is a major consumer of blood products, and hemodilution increases transfusion requirements during cardiac surgery under CPB. As intraoperative parenteral fluids contribute to hemodilution, we evaluated the hypothesis that intraoperative fluid restriction reduces packed red-cell (PRC use, especially in transfusion-prone adults undergoing elective cardiac surgery. Methods 192 patients were randomly assigned to restrictive (group A, 100 pts, or liberal (group B, 92 pts intraoperative intravenous fluid administration. All operations were conducted by the same team (same surgeon and perfusionist. After anesthesia induction, intravenous fluids were turned off in Group A (fluid restriction patients, who only received fluids if directed by protocol. In contrast, intravenous fluid administration was unrestricted in group B. Transfusion decisions were made by the attending anesthesiologist, based on identical transfusion guidelines for both groups. Results 137 of 192 patients received 289 PRC units in total. Age, sex, weight, height, BMI, BSA, LVEF, CPB duration and surgery duration did not differ between groups. Fluid balance was less positive in Group A. Fewer group A patients (62/100 required transfusion compared to group B (75/92, p Conclusions Our data suggest that fluid restriction reduces intraoperative PRC transfusions without significantly increasing postoperative transfusions in cardiac surgery; this effect is more pronounced in transfusion-prone patients. Trial registration NCT00600704, at the United States National Institutes of Health.

  13. Red cell concentrates of hemochromatosis patients comply with the storage guidelines for transfusion purposes.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Rombout-Sestrienkova, E.; Grip, W.J. de; Bos, H.J.; Bosman, G.J.C.G.M.

    2008-01-01

    BACKGROUND: Therapeutic phlebotomy is the preferred treatment for iron overload associated with hemochromatosis. In the Netherlands, red blood cell concentrates (RCCs) from hemochromatosis patients are not used for transfusion purposes. In this study, their storage performance was compared with that

  14. Duration of red blood cell storage and survival of transfused patients (CME)

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Kamper-Jørgensen, Mads; Eloranta, Sandra;

    2010-01-01

    Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.......Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time....

  15. Incidence of Red Cell Alloantibody among the Transfusion Recipients of Universiti Kebangsaan Malaysia Medical Centre

    OpenAIRE

    Yousuf, Rabeya; Abdul Aziz, Suria; Yusof, Nurasyikin; Leong, Chooi Fun

    2012-01-01

    Red blood cell alloimmunization is a common complication among the transfusion recipients. In Malaysia, multiple ethnicity causes genetic heterogeneity among the population which in turn can cause a wide variation of antibody. The objective of this study was to analyse the red cell alloantibody detected during the pre-transfusion testing. This was a cross-sectional study done in the blood bank of Universiti Kebangsaan Malaysia Medical Centre during the period of January–December 2010. The dat...

  16. Accelerated clearance of human red blood cells in a rat transfusion model

    OpenAIRE

    Straat, M.; Klei, TRL; de Korte, D; van Bruggen, R.; Juffermans, NP

    2015-01-01

    Background Animal models are valuable in transfusion research. Use of human red blood cells (RBCs) in animal models facilitates extrapolation of the impact of storage conditions to the human condition but may be hampered by the use of cross species. Methods Investigation of clearance and posttransfusion recovery in a rat model using fresh and stored human RBCs. Results Directly following transfusion, human RBCs could be detected in the circulation of all recipients, with higher recovery rates...

  17. Application of reticulated platelets to transfusion management during autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Parco S

    2012-01-01

    Full Text Available Sergio Parco, Fulvia VascottoInstitute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, ItalyBackground: The immature (or reticulated platelet fraction (IPF is rich in nucleic acids, especially RNA, and can be used as a predictive factor for platelet recovery in platelet immunomediated consumption or in postchemotherapy myelosuppression. Our aim was to determine if transfusions with IPF-rich solutions, during autologous peripheral blood stem cell transplantation, reduce the occurrence of bleeding and hemorrhagic complications.Patients and methods: Transfusions were administered to 40 children, affected with hematological pathologies, who underwent autologous peripheral hematopoietic progenitor cell transplantation. There were two groups of 20 patients, one group treated with IPF-poor and the other with IPF-rich solutions. In the two groups, the conditioning regimen was the same for the same pathology (hematological pathologies: 14 acute lymphoblastic leukemia; twelve acute myelocytic leukemia; four non-Hodgkin's lymphoma; two Hodgkin's lymphoma; eight solid tumors. A new automated analyzer was used to quantify the IPF: the XE2100 (Sysmex, Kobe, Japan blood cell counter with upgraded software.Results: The 20 patients who received solutions with a high percentage of IPF (3%–9% of total number of infused platelets required fewer transfusions than the 20 patients who received transfusions with a low percentage of IPF (0%–1% of total number of infused platelets: 83 versus 129 (mean of number of transfusions 4.15 versus 6.45 and a significant difference was found between the two groups by using the Mann–Whitney test (P < 0.001. The prophylactic transfusions decreased from three to two per week. There was only one case of massive hemorrhage.Conclusion: The use of IPF solutions reduces the number of transfusions and bleedings after peripheral blood stem cell transplantation in pediatric patients.Keywords: children, reticulated

  18. Respiratory Impairment after Early Red Cell Transfusion in Pediatric Patients with ALI/ARDS

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    Surender Rajasekaran

    2012-01-01

    Full Text Available Introduction. In the first 48 hours of ventilating patients with acute lung injury (ALI/acute respiratory distress syndrome (ARDS, a multipronged approach including packed red blood cell (PRBC transfusion is undertaken to maintain oxygen delivery. Hypothesis. We hypothesized children with ALI/ARDS transfused within 48 hours of initiating mechanical ventilation would have worse outcome. The course of 34 transfused patients was retrospectively compared to 45 nontransfused control patients admitted to the PICU at Helen DeVos Children’s Hospital between January 1st 2008 and December 31st 2009. Results. Mean hemoglobin (Hb prior to transfusion was 8.2 g/dl compared to 10.1 g/dl in control. P/F ratio decreased from 135.4±7.5 to 116.5±8.8 in transfused but increased from 148.0±8.0 to 190.4±17.8 (P<0.001 in control. OI increased in the transfused from 11.7±0.9 to 18.7±1.6 but not in control. Ventilator days in the transfused were 15.6±1.7 versus 9.5±0.6 days in control (P<0.001. There was a trend towards higher rates of MODS in transfused patients; 29.4% versus 17.7%, odds ratio 1.92, 95% CI; 0.6–5.6 Fisher exact P<0.282. Conclusion. This study suggests that early transfusions of patients with ALI/ARDS were associated with increased ventilatory needs.

  19. MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Hurlet, A. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Comerci, S.C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Piomelli, S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States)

    1995-11-01

    Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusion-dependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis, and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques. (orig.). With 4 figs., 2 tabs.

  20. Utilization and quality of cryopreserved red blood cells in transfusion medicine

    NARCIS (Netherlands)

    Henkelman, S.; Noorman, F.; Badloe, J. F.; Lagerberg, J. W. M.

    2015-01-01

    Cryopreserved (frozen) red blood cells have been used in transfusion medicine since the Vietnam war. The main method to freeze the red blood cells is by usage of glycerol. Although the usage of cryopreserved red blood cells was promising due to the prolonged storage time and the limited cellular det

  1. Clinical observation of factors in the efficacy of blood component transfusion in patients following hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    Full Text Available BACKGROUND: Factors affecting the efficacy of platelet and red blood cell (RBC transfusion in patients undergoing hematopoietic stem cell transplantation (HSCT have not been studied extensively. We aimed to evaluate platelet and RBC transfusion efficacy by measuring the platelet corrected count increment and the hemoglobin increment, respectively, 24 h after transfusion in 105 patients who received HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Using retrospective analysis, we studied whether factors, including gender, time of transplantation, the compatibility of ABO group between HSC donors and recipients, and autologous or allogenic transplantation, influence the efficacy of blood component transfusion. We found that the infection rate of HSCT patients positively correlated with the transfusion amount, and the length of stay in the laminar flow room was associated with transfusion. We found that platelet transfusion performed during HSCT showed significantly better efficacy than that performed before HSCT. The effect of platelet transfusion in auto-transplantation was significantly better than that in allo-transplantation. The efficacy of RBC transfusion during HSCT was significantly lower than that performed before HSCT. The efficacy of RBC transfusion in auto-transplantation was significantly higher than that in allo-transplantation. Allo-transplantation patients who received HSCs from compatible ABO groups showed significantly higher efficacy during both platelet and RBC transfusion. CONCLUSIONS: We conclude that the efficacy of platelet and RBC transfusions does not correlate with the gender of patients, while it significantly correlates with the time of transplantation, type of transplantation, and ABO compatibility between HSC donors and recipients. During HSCT, the infection rate of patients positively correlates with the transfusion amount of RBCs and platelets. The total volume of RBC units transfused positively correlates with the length of

  2. The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice

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    David R. Gibb

    2016-07-01

    Full Text Available Red blood cell (RBC transfusions are essential for patients with hematological disorders and bone marrow failure syndromes. Despite ABO matching, RBC transfusions can lead to production of alloantibodies against “minor” blood group antigens. Non-ABO alloimmunization is a leading cause of transfusion-associated mortality in the U.S. Despite its clinical importance, little is known about the immunological factors that promote alloimmunization. Prior studies indicate that inflammatory conditions place patients at higher risk for alloimmunization. Additionally, co-exposure to pro-inflammatory pathogen associated molecular patterns (PAMPs promotes alloimmunization in animal models, suggesting that RBC alloimmunization depends on innate immune cell activation. However, the specific innate immune stimuli and sensors that induce a T cell-dependent alloantibody response to transfused RBCs have not been identified. The NLRP3 inflammasome senses chemically diverse PAMPs and damage associated molecular patterns (DAMPs, including extracellular ATP and iron-containing heme. We hypothesized that activation of the NLRP3 inflammasome by endogenous DAMPs from RBCs promotes the alloimmune response to a sterile RBC transfusion. Using genetically modified mice lacking either NLRP3 or multiple downstream inflammasome response elements, we ruled out a role for the NLRP3 inflammasome or any Caspase-1 or -11 dependent inflammasome in regulating RBC alloantibody production to a model antigen.

  3. Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia, and Other Transfusion Complications.

    Science.gov (United States)

    Fasano, Ross M; Chou, Stella T

    2016-10-01

    Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required. DNA-based red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia. High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping technology for both patient and donor populations may be transformative for the field of transfusion medicine. PMID:27345938

  4. Reducing red cell transfusion by audit, education and a new guideline in a large teaching hospital.

    Science.gov (United States)

    Garrioch, M; Sandbach, J; Pirie, E; Morrison, A; Todd, A; Green, R

    2004-02-01

    Safety concerns combined with the greatly increased costs and difficulties of maintaining the blood supply are major considerations for transfusion services. Previous local surveys demonstrated that hospital blood use at our hospital could be improved. Excessive cross-matching, unnecessary transfusion and high return rates of unused blood were commonplace. Transfusion practice was audited over a 3-month period. An education package with guidelines for transfusion was delivered to all clinician groups within the hospital, over the following 9 months. The audit was repeated exactly 1 year later at the same time period. During the second audit, inpatient hospital numbers increased by 1.02% (from n = 7262 to n = 7336) but no differences in length of stay, cardiovascular morbidity or mortality were demonstrated. Twenty percent (n = 254, 2002; n = 316, 2001) fewer patients received blood, and the number of red cell packs used reduced by 19% (from n = 1093 to n = 880). Total number of patients transfused reduced from 4.4% to 3.5% which, as an absolute difference, is a reduction of 0.9% (CI 0.3-1.5, P = 0.006). The audit, guideline and education package had a major impact on red cell use within the hospital with no adverse effects. Blood use can be improved by the implementation of a suitable education package and guideline. If it is possible to replicate the results of this education programme nationwide, the effect on blood use, with subsequent savings and enhanced patient safety could be significant.

  5. Transfusion rate and prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease

    DEFF Research Database (Denmark)

    Thoestesen, Lisbeth M; Rasmussen, Kjeld L; Lauszus, Finn F;

    2011-01-01

    To determine transfusion rates, risk factors for transfusion and the prevalence of unexpected red blood cell alloantibodies in women undergoing hysterectomy for benign disease. In addition, we aimed to evaluate the necessity of the pretransfusion testing for red blood cell alloantibodies....

  6. Predictors of red blood cell transfusion after cardiac surgery: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Camila Takao Lopes

    2015-12-01

    Full Text Available Abstract OBJECTIVE To identify predictors of red blood cell transfusion (RBCT after cardiac surgery. METHOD A prospective cohort study performed with 323 adults after cardiac surgery, from April to December of 2013. A data collection instrument was constructed by the researchers containing factors associated with excessive bleeding after cardiac surgery, as found in the literature, for investigation in the immediate postoperative period. The relationship between risk factors and the outcome was assessed by univariate analysis and logistic regression. RESULTS The factors associated with RBCT in the immediate postoperative period included lower height and weight, decreased platelet count, lower hemoglobin level, higher prevalence of platelet count <150x10 3/mm3, lower volume of protamine, longer duration of anesthesia, higher prevalence of intraoperative RBCT, lower body temperature, higher heart rate and higher positive end-expiratory pressure. The independent predictor was weight <66.5Kg. CONCLUSION Factors associated with RBCT in the immediate postoperative period of cardiac surgery were found. The independent predictor was weight.

  7. Transfusion of RHD negative patients with RHD positive red cells concentrates: the HPFF, EPE Blood Department experience (2002-2010)

    OpenAIRE

    Barra, A.; Barradas, A; Cardoso, E; C. Costa; A. Fontes; Gil, A.; Oliveira, C.; Pereira, F; Rebelo, S.

    2011-01-01

    Background: In transfusion practice we should respect the ABO group and the Rh phenotype. The lack of availability of red cells concentrates [RCC] RhD negative in the quantities desired, do nol always make it possible to satisfy that requirement, especially in urgency. In our practice we never transfuse RhD in some groups of patients RhD negative, like women of childbearing age, children, newborns, patients with disease likely to need multiple transfusions [eg oncologic patients]. Alms: ...

  8. Storage duration of red blood cell transfusion and Clostridium difficile infection: a within person comparison.

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    Mary A M Rogers

    Full Text Available OBJECTIVE: Randomized controlled trials demonstrated that red blood cell (RBC transfusion elevates the risk of infection, and trials are underway to evaluate whether RBC storage affects outcomes. We previously reported that transfusion predicts Clostridium difficile infection (CDI and, therefore, planned an investigation to examine this further using a more robust design. DESIGN: Within-person case-crossover study. Hospitalizations in which CDI developed (n = 406 were compared to hospitalizations for the same individuals in which CDI did not occur (n = 949. Transfusion volume and storage duration were assessed prior to the onset of CDI. SETTING: University of Michigan Health System. PATIENTS: Participants were individuals with a diagnosis of CDI from July 2009 through June 2012. MEASUREMENTS AND MAIN RESULTS: During the hospitalizations when CDI occurred, 34.7% of the patients received allogeneic RBC transfusions (mean volume, 688 ml compared to 19.0% of patients in hospitalizations without CDI (mean volume, 180 ml. The odds of healthcare-associated CDI increased by 76% (95% CI 1.39-2.23 for every liter of RBCs transfused and was elevated in both nonsurgical (OR = 1.90 and surgical (OR = 1.86 hospitalizations. In patients who received RBC transfusions, the odds of developing CDI increased by 6% for every additional day of RBC stored and by 53% for every week of additional storage (P = 0.002. CONCLUSIONS: Hospitalizations in which a patient received a greater volume of RBC transfusions were more likely to be associated with the development of CDI. RBC units stored for a longer duration were associated with the development of healthcare-associated CDI after adjustment for RBC volume.

  9. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq.

    Science.gov (United States)

    Al-Mousawi, Muqdad M N; Al-Allawi, Nasir A S; Alnaqshabandi, Rubad

    2015-01-01

    Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C(w), anti-C, anti-c and anti-Le(a). Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p = 0.005), Rhesus D (RhD) negative status (p = 0.0017) and history of previous transfusion reactions (p = 0.007) showed a statistically significant higher rate of alloimmunization. However, patients' age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions. PMID:26327166

  10. Blood Transfusion

    Science.gov (United States)

    ... to infections including those we develop from our vaccinations (such as poliovirus antibodies, which are made by ... the Transfusion Medicine Unit, Blood Bank, and Stem Cell Storage Facility University of Rochester Medical ... and health educators who are available by phone Monday through Friday, 9 am to 9 pm ( ...

  11. Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Alexander, Paul E; Barty, Rebecca; Fei, Yutong; Vandvik, Per Olav; Pai, Menaka; Siemieniuk, Reed A C; Heddle, Nancy M; Blumberg, Neil; McLeod, Shelley L; Liu, Jianping; Eikelboom, John W; Guyatt, Gordon H

    2016-01-28

    The impact of transfusing fresher vs older red blood cells (RBCs) on patient-important outcomes remains controversial. Two recently published large trials have provided new evidence. We summarized results of randomized trials evaluating the impact of the age of transfused RBCs. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Database for Systematic Reviews, and Cochrane CENTRAL for randomized controlled trials enrolling patients who were transfused fresher vs older RBCs and reported outcomes of death, adverse events, and infection. Independently and in duplicate, reviewers determined eligibility, risk of bias, and abstracted data. We conducted random effects meta-analyses and rated certainty (quality or confidence) of evidence using the GRADE approach. Of 12 trials that enrolled 5229 participants, 6 compared fresher RBCs with older RBCs and 6 compared fresher RBCs with current standard practice. There was little or no impact of fresher vs older RBCs on mortality (relative risk [RR], 1.04; 95% confidence interval [CI], 0.94-1.14; P = .45; I(2) = 0%, moderate certainty evidence) or on adverse events (RR, 1.02; 95% CI, 0.91-1.14; P = .74; I(2) = 0%, low certainty evidence). Fresher RBCs appeared to increase the risk of nosocomial infection (RR, 1.09; 95% CI, 1.00-1.18; P = .04; I(2) = 0%, risk difference 4.3%, low certainty evidence). Current evidence provides moderate certainty that use of fresher RBCs does not influence mortality, and low certainty that it does not influence adverse events but could possibly increase infection rates. The existing evidence provides no support for changing practices toward fresher RBC transfusion. PMID:26626995

  12. Haemolysis following rapid experimental red blood cell transfusion--an evaluation of two infusion pumps

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Sprogøe-Jakobsen, U; Pedersen, C M;

    1998-01-01

    The vast majority of infusion pumps used for rapid transfusion of large amounts of blood have never been properly examined regarding their influence on the quality of the red blood cells (RBCs) infused. In this study, we evaluated the effect of two different infusion pumps on the degree of RBC...

  13. Survival of the fittest?--survival of stored red blood cells after transfusion.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Bost, H.J.; Bosman, G.J.C.G.M.

    2004-01-01

    During the last 90 years many developments have taken place in the world of blood transfusion. Several anticoagulants and storage solutions have been developed. Also the blood processing has undergone many changes. At the moment, in The Netherlands, red blood cell (RBC) concentrates (prepared from a

  14. Transfusion of D+ red blood cells to D- individuals in trauma situations.

    Science.gov (United States)

    Tchakarov, Amanda; Hobbs, Rhonda; Bai, Yu

    2014-01-01

    To conserve D- red blood cells (RBCs), our facility developed a policy for transfusion of D+ units to D- patients, particularly in trauma situations. To our knowledge, this is the first study looking at D-mismatched RBC transfusion in trauma patients. We developed guidelines for the transfusion of D-mismatched RBCs. patients were followed by anti body screening and direct antiglobulin testing. Twenty-six patients were identified, and 57.7 percent of the cases were the result of trauma. Follow-up ranged from 7 to 455 days. The trauma cohort had a follow-up of 7 to 102 days. Overall, patients were transfused with 1 to 36 units of D-mismatched RBCs. Three patients produced alloanti-D, resulting in a 20 percent rate of antibody formation rate of 11.5 percent compared with 21.4 to 30.4 percent in previous studies. Approximately 58 percent of our study population was composed of trauma patients. Within that cohort, the formation of anti-D was 20 percent, similar to the rate seen in previous studies looking at primarily non-trauma populations. PMID:25831260

  15. Partial exchange transfusion in a patient with homozygous sickle cell disease undergoing heart surgery with cardiopulmonary bypass: a case report

    OpenAIRE

    Deyvis Cruz

    2012-01-01

    In patients with sickle cell anemia, the extracorporeal circulation circuit promotes the polymerization of hemoglobin and sickle cell formation. Exchange transfusion reduces circulating levels of hemoglobin S. We report the management of a child with homozygous sickle cell anemia who required surgical closure of atrial septal defect. Partial intraoperative exchange transfusion was performed that decreased hemoglobin S levels from 89% to 23%. Cardiopulmonary bypass was conducted at normothermi...

  16. Evaluation of Hematological Parameters in Partial Exchange and Packed Cell Transfusion in Treatment of Severe Anemia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Sudha Salhan

    2012-01-01

    Full Text Available Objectives. Anemia is a major public health problem throughout the world which assumes prominence in pregnant mothers. Patients with severe anemia continue to present themselves at term or in labor. This study was conducted to compare the improvements in hematological parameters of patients receiving partial exchange blood transfusion and transfusion of packed cells without exchange. Methods. One hundred and twenty-five severely anemic antenatal mothers were admitted from outpatient service. Partial exchange transfusion was given to sixty-six patients while fifty-nine received transfusion of packed cells with frusemide cover. Results. The two groups were comparable in terms of age, height, weight, religion, diet, education, occupation of self and husband, and income. Hemoglobin level in Group 1 was comparatively less than Group 2 at prelevel (5.2±1.5 versus 6.6±2.3, P=0.001 and postlevel (7.2±1.5 versus 8.6±1.8, P=0.001, respectively, but there was no significant difference between the two modes of transfusion (2.09±1.6 versus 2.01±1.5, P=0.78. Conclusion. The study produced an equally significant improvement in hematological parameters in partial exchange and packed cell transfusion. Platelet counts were significantly less in partial exchange as compared with packed cell transfusion.

  17. Health-related quality of life in children with sickle cell anemia: impact of blood transfusion therapy.

    Science.gov (United States)

    Beverung, Lauren M; Strouse, John J; Hulbert, Monica L; Neville, Kathleen; Liem, Robert I; Inusa, Baba; Fuh, Beng; King, Allison; Meier, Emily Riehm; Casella, James; DeBaun, Michael R; Panepinto, Julie A

    2015-02-01

    The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre-existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health-related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group. A total of 89% (175 of 196) of the randomly allocated participants had evaluable entry and exit HRQL evaluations. The increase in Change in Health, measured as the child's health being better, was significantly greater for the transfusion group than the observation group (difference estimate = -0.54, P ≤ 0.001). This study provides the first evidence that children with SCA who received regular blood transfusion therapy felt better and had better overall HRQL than those who did not receive transfusion therapy.

  18. Admission red cell distribution width: a novel predictor of massive transfusion after injury.

    Science.gov (United States)

    Paulus, Elena M; Weinberg, Jordan A; Magnotti, Louis J; Sharpe, John P; Schroeppel, Thomas J; Fabian, Timothy C; Croce, Martin A

    2014-07-01

    Admission red cell distribution width (aRDW) has been shown to predict mortality in trauma patients by an unclear mechanism. It has been speculated that aRDW is a marker of chronic health status, but elevated RDW may also reflect recent hemorrhage. We hypothesized that aRDW is a predictor of major hemorrhage in trauma patients. Shock trauma patients at a Level I trauma center over 6.5 years were evaluated. Patients were stratified by aRDW quintile (Q1: less than 13%, Q2: 13.1 to 13.5%, Q3: 13.6 to 14.0%, Q4: 14.1 to 14.9%, Q5: 15.0% or greater). Massive transfusion (MT) was defined as 10 or more packed red blood cells in the first 24 hours. From multiple logistic regression, odds ratios with 95 per cent confidence intervals (CIs) were determined to evaluate the association between aRDW quintile and MT. Three thousand nine hundred ninety-four met study criteria. Overall MT incidence was 10 per cent and in-hospital mortality was 17 per cent. MT and mortality increased in a stepwise fashion by aRDW quintile (P < 0.0001). From logistic regression, a threefold increased odds of MT was associated with aRDW Q4 (CI, 1.81 to 4.92), and a 3.5-fold increased odds of MT was associated with aRDW Q5 (CI, 2.70 to 5.83). aRDW independently predicted MT, suggesting that elevated aRDW is an indicator of major hemorrhage in trauma patients. The association between aRDW and mortality in trauma patients may be explained by acute hemorrhage rather than chronic health status.

  19. Post-transfusion purpura treated with plasma exchange by haemonetics cell separator. A case report

    DEFF Research Database (Denmark)

    Laursen, B; Morling, N; Rosenkvist, J;

    1978-01-01

    A case of post-transfusion purpura in a 61-year-old, multiparous female with a platelet alloantibody (anti-Zwa) in her serum is reported. The patient was successfully treated with plasma exchange by means of a Haemonetics 30 cell separator and corticosteroids. Compared with other therapeutic...... measures, plasma exchange seems to shorten the duration of thrombocytopenia. Major surgery was possible in our patient within ten days of development of the syndrome....

  20. Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock

    OpenAIRE

    Parsons, Elizabeth C.; Hough, Catherine L.; Seymour, Christopher W; Cooke, Colin R.; Rubenfeld, Gordon D.; Watkins, Timothy R

    2011-01-01

    Introduction In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock. Methods We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor ...

  1. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    Science.gov (United States)

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (pvolume from 39.7 to 64.1 ml/m2 (pvolume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  2. Breast cancer tumor growth is efficiently inhibited by dendritic cell transfusion in a murine model

    Directory of Open Access Journals (Sweden)

    Viet Quoc Pham

    2014-03-01

    Full Text Available The ability of dendritic cells to efficiently present tumor-derived antigens when primed with tumor cell lysates makes them attractive as an approach for cancer treatment. This study aimed to evaluate the effects of dendritic cell transfusion dose on breast cancer tumor growth in a murine model. Dendritic cells were produced from allogeneic bone marrow-derived mononuclear cells that were cultured in RPMI 1640 medium supplemented with 20 ng/mL GM-CSF and 20 ng/mL IL-4 for 7 days. These cells were checked for maturation before being primed with a cancer cell-derived antigen. Cancer cell antigens were produced by a rapid freeze-thaw procedure using a 4T1 cell line. Immature dendritic cells were loaded with 4T1 cellderived antigens. Dendritic cells were transfused into mice bearing tumors at three different doses, included 5.104, 105, and 106 cells/mouse with a control consisting of RPMI 1640 media alone. The results showed that dendritic cell therapy inhibited breast cancer tumors in a murine model; however, this effect depended on dendritic cell dose. After 17 days, in the treated groups, tumor size decreased by 43%, 50%, and 87.5% for the doses of 5 and times; 104, 105, and 106 dendritic cells, respectively, while tumor size in the control group decreased by 44%. This result demonstrated that dendritic cell therapy is a promising therapy for breast cancer treatment. [Biomed Res Ther 2014; 1(3.000: 85-92

  3. Proven and potential clinical benefits of washing red blood cells before transfusion: current perspectives

    Directory of Open Access Journals (Sweden)

    Schmidt AE

    2016-08-01

    Full Text Available Amy E Schmidt, Majed A Refaai, Scott A Kirkley, Neil Blumberg Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA Abstract: Red blood cells (RBCs are washed for a variety of reasons such as to remove excess potassium, cytokines, and other allergen proteins from the supernatant and/or to mitigate the effects of the storage lesion. The storage lesion is a product of RBC aging and include leakage of potassium and chloride from the RBCs, depletion of 2,3-diphosphoglycerate and adenosine triphosphate, loss of phospholipids and cholesterol, exposure of phosphatidylserine, elaboration of lipid mediators, loss of glutathione, autoxidation of hemoglobin to methemoglobin contributing to decreased blood flow viscosity and adherence to endothelial cells, increased microparticle formation, and disruption of NO-mediated vasodilation. A storage lesion is thought to be caused in part by oxidative stress, which is characterized by functional and structural changes to the RBCs. The effects of the RBC storage lesion on patient morbidity and mortality have been studied intensively with mixed results. Here, we will summarize the potential benefits of RBC washing. Notably, all patient-based studies on washed RBCs are single-center, small randomized studies or observational data, which await replication and tests of generalizability. Some of the most promising preliminary data suggest that washed transfusions of red cells and platelets reduce mortality in low risk, younger patients with acute myeloid leukemia, mitigate lung injury, and substantially reduce mortality in cardiac surgery. Larger randomized trials to replicate or refute these findings are urgently needed and, most importantly, have the potential to strikingly improve clinical outcomes following transfusion. Keywords: washed blood, transfusion, immunomodulation, red blood cell

  4. A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440

    Directory of Open Access Journals (Sweden)

    Rowe Jacob M

    2004-12-01

    Full Text Available Abstract Background Platelet transfusion is universally employed in acute leukemia. Platelet concentrate supernatants contain high concentrations of biologic mediators that might impair immunity. We investigated whether washed platelet and red cell transfusions could improve clinical outcomes in adult patients with acute leukemia. Methods A pilot randomized trial of washed, leukoreduced ABO identical transfusions versus leukoreduced ABO identical transfusions was conducted in 43 adult patients with acute myeloid or lymphoid leukemia during 1991–94. Primary endpoints to be evaluated were platelet transfusion refractoriness, infectious and bleeding complications and overall survival. Results There were no significant differences in infectious or major bleeding complications and only one patient required HLA matched platelet transfusions. Minor bleeding was more frequent in the washed, leukoreduced arm of the study. Confirmed transfusion reactions were more frequent in the leukoreduced arm of the study. Overall survival was superior in the washed arm of the study (40% versus 22% at 5 years, but this difference was not statistically significant (p = 0.36. A planned subset analysis of those ≤50 years of age found that those in the washed, leukoreduced arm (n = 12 had a 75% survival at five years compared with 30% in the leukoreduced arm (n = 10 (p = 0.037 Conclusion This study provides the first evidence concerning the safety and efficacy of washed platelets, and also raises the possibility of improved survival. We speculate that transfusion of stored red cell and platelet supernatant may compromise treatment, particularly in younger patients with curable disease. Larger trials will be needed to assess this hypothesis.

  5. Exchange transfusion for severe malaria: A comparison of red cell exchange with whole blood exchange

    Directory of Open Access Journals (Sweden)

    Udani S

    2003-01-01

    Full Text Available Aim: To compare exchange transfusions done for severe malaria using the traditional whole blood exchange method with therapeutic red cell exchange (TREX done using a Cobe spectra cell separator. Methods: 6 children with acute, severe malaria and parasitic infestation rates (IR >50% with multi organ failure, were subjected to exchange transfusions. 3 had whole blood single volume exchanges and 3 had TREX using the Cobe-Spectra cell separator. The two groups were compared for difficulties encountered, time taken, complications, quantity of blood products used, metabolic and hematological derangements and fall in IR. Results: The TREX took less time per 100 ml of blood exchanged, resulted in a 24% more efficient decrease in the IR and required less donor plasma. 3/3 tolerated the TREX well whereas one child had complications of hypocalcemia and acidosis with the whole blood exchange. The rise in hemoglobin/hematocrit was comparable in both and the platelet count was not significantly altered in either group. There was no significant alteration in the DIC profile in either group. All 6 children recovered within comparable time frames. Conclusion: The TREX was safer, more efficacious and less time consuming. This procedure is recommended whenever available for red cell exchange in malaria.

  6. Red blood cell transfusion and mortality in trauma patients: risk-stratified analysis of an observational study.

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    Pablo Perel

    2014-06-01

    Full Text Available BACKGROUND: Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC transfusion with mortality according to the predicted risk of death. METHODS AND FINDINGS: A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: 50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8% received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction 50% predicted risk of death (OR 0.59, 95% CI 0.47-0.74, p<0.0001. Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05-3.24, p<0.0001. The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6% predicted risk of death (p-value for interaction <0.0001. As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were

  7. Observation on the changes of serum erythropoietin (EPO) and ferritin (SF) levels after preserved red cells (PRC) transfusion in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum EPO and SF levels after preserved red cells transfusion in patients with IDA. Methods: Serum EPO and SF levels were detected with RIA both before and after transfusing preserved red cells in 35 patients with IDA as well as in 30 controls. Results: Before transfusion serum EPO levels in the patients were significantly higher than those in the controls (P0.05). Conclusion: Transfusing preserved red cells is an effective treatment and has important role in clinical application. (authors)

  8. The Status of Packed Red Blood Cell Transfusion in Besat Hospital of Hamadan in 2009-2010

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    RafieemehrH

    2011-01-01

    Full Text Available Bakground and objectives: Higher than the needed blood orders not onlyadversely affect blood quality but also impose extra expenses on therapeuticcenter and patients. We aimed at determining the frequency of packed redblood cell transfusion in Besat hospital of Hamadan in 2009-2010.Material and Methods: This descriptive study was carried out on 926 bloodorder forms in Besat hospital. The data were collected, using blood orderforms, in Hamedan teaching hospital (Besat from March 2009 to march 2010.We assessed the amount of blood order, blood consumption,crossmatch/transfusion ratio(C/T and transfusion index (TI in different wardsof hospital.Results: Out of 926 patients aged averagely 28, 37% were females and 63%are males. The overall ratio of C/T and TI is 2.44 and 0/63, respectively. Theyare considered to be optimal, in comparison with the standard figures ofC/T<2.5 and TI≥0.5.The results show that the highest C/T is in surgery wardand the lowest in burn ward. But the highest TI is related to Hematology wardand the lowest to urology ward.Conclusion: Packed cell consumption, C/T Ratio and TI in Besat hospitals arenormal but not ideal.It seems that absence of hospital blood transfusioncommittees and lack of active contribution of physicians, are the majorobstacles in reforming blood utilization.Key words: Packed cell, crossmatch,transfusion index, transfusion

  9. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E;

    1997-01-01

    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patients...... who received a single series of blood transfusions. They received mostly saline-adenine-glucose+mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal...... (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous...

  10. Severe hemolytic transfusion reaction due to anti-D in a D+ patient with sickle cell disease

    OpenAIRE

    Ipe, Tina S.; Wilkes, Jennifer J.; Hartung, Helge D.; Westhoff, Connie M.; Chou, Stella T.; Friedman, David F.

    2015-01-01

    A 5-year-old male with sickle cell disease presented with pain, dark urine, and fatigue 10 days after a red blood cell (RBC) transfusion. Laboratory evaluation demonstrated severe anemia, blood type O+, and anti-D in the serum. Anti-D in a D+ patient led to RH genotyping which revealed homozygosity for RHD*DAU4 that encodes partial D antigen. Anti-D in this patient whose RBCs exclusively express partial D caused a delayed hemolytic transfusion reaction after exposure to D+ RBCs. The finding o...

  11. Alloimmunization screening after transfusion of red blood cells in a prospective study Pesquisa de aloimunização após transfusão de concentrados de hemácias em um estudo prospectivo

    OpenAIRE

    Vitor Mendonça Alves; Paulo Roberto Juliano Martins; Sheila Soares; Gislene Araújo; Luciana Cayres Schmidt; Sidneia Sanches de Menezes Costa; Dante Mário Langhi; Helio Moraes-Souza

    2012-01-01

    BACKGROUND: Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients. OBJECTIVE: a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM), Brazil was performed to correlate alloimmunization to clinical and epi...

  12. Enhancement of Antibody Titre and Development of Additional Red Cell Alloantibodies Following Intrauterine Transfusion.

    Science.gov (United States)

    Dubey, Anju; Sonker, Atul; Chaudhary, Rajendra

    2016-03-01

    Intrauterine blood transfusion is the mainstay of managing foetuses with severe anemia. It may however result in fetomaternal hemorrhage, which in cases of Rh isoimmunisation may increase the severity of the disease by enhancing the maternal immunological response to fetal antigens. This study was conducted to determine the frequency, specificity and origin of additional red cell antibodies which developed after IUT. The change in the titre of allo anti-D following IUT was also determined. Antibody detection and titration was done on the blood samples of all the patients before and after intrauterine blood transfusion to check for the development of additional antibody and change in the titre of existing anti-D. Severe anemia was found in 17 (58.6 %) fetuses who received a total of 42 ultrasound-guided IUTs. Development of antibodies additional to anti-D in maternal serum was seen in 5 (29.4 %) cases. The specificity of additional alloantibodies was anti-C in four cases whereas it was anti-E in one case. Four fold or greater increase in existing allo-anti D titre was seen in 6 (35.3 %) cases after IUT. Enhancement of maternal sensitisation leading to an increase in maternal antibody titre is particularly seen after the first IUT. Matching of the donor RBCs particularly for Rh antigens might prevent the induction of additional alloantibodies against these antigens. IUT as a treatment modality should be given judiciously and only when the need is inevitable. PMID:26855513

  13. The clinical effects of red blood cell transfusions: an overview of the randomized controlled trials evidence base.

    Science.gov (United States)

    Wilkinson, Kirstin L; Brunskill, Susan J; Dorée, Carolyn; Hopewell, Sally; Stanworth, Simon; Murphy, Mike F; Hyde, Chris

    2011-04-01

    No up-to-date overview of randomized controlled trials (RCTs) in red blood cell (RBC) transfusion exists. This systematic review examines the quantity and quality of the evidence for the clinical effects of RBC transfusion. One hundred forty-two eligible RCTs were identified through searches of The Cochrane Library (issue 4, 2009), MEDLINE (1950 to November 2009), EMBASE (1974 to November 2009), and other relevant sources. After data extraction and methodological quality assessment, trials were grouped by clinical specialty and type of RBC transfusion. Data analysis was predominantly descriptive. The 142 RCTs covered 11 specialties and 10 types of RBC transfusion. The number of included patients varied widely across the RCTs (median, 57; IQ range, 27-167). Most trials were single center comparing 2 parallel study arms. Overall, the reporting of methodological assessment was poor, although it improved markedly from 2001. Clinical areas with few trials are highlighted. Comparison with a study of RBC use in clinical practice highlighted a lack of correlation between the size of the evidence base for a given clinical specialty and the proportion of total RBC use by that clinical specialty. The gaps in the evidence base and the poor methodology of trials particularly in the past do not provide a strong evidence base for the use of RBC transfusions, but they indicate important targets for future research. PMID:21345644

  14. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications. PMID:26133961

  15. Acute liver function decompensation in a patient with sickle cell disease managed with exchange transfusion and endoscopic retrograde cholangiography

    OpenAIRE

    Papafragkakis, Haris; Mel A. Ona; Changela, Kinesh; Sadanandan, Swayamprabha; Jelin, Abraham; Anand, Sury; Duddempudi, Sushil

    2014-01-01

    Sickle cell intrahepatic cholestasis is a relatively uncommon complication of homozygous sickle cell anemia, which may lead to acute hepatic failure and death. Treatment is mainly supportive, but exchange transfusion is used as salvage therapy in life threatening situations. We describe a case of a 16-year-old female with homozygous sickle cell anemia who presented to the emergency room with fatigue, malaise, dark urine, lower back pain, scleral icterus and jaundice. She was found to have mar...

  16. No early effect of storage time of transfused red blood cells on fatigue and plasma cytokines in patients with anaemia from non-acute gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Mynster, Tommie; Dziegiel, Morten H; Kofoed, Kristian

    2007-01-01

    Background: Fatigue in anaemia is empirically reduced by blood transfusion. Long storage time of red cells may be associated with immunomodulatory effects, and blood stored for a long time may cause tissue hypoxia upon transfusion. Patients and Methods: 22 patients admitted with haemoglobin

  17. Transfusion practices in trauma

    Directory of Open Access Journals (Sweden)

    V Trichur Ramakrishnan

    2014-01-01

    Full Text Available Resuscitation of a severely traumatised patient with the administration of crystalloids, or colloids along with blood products is a common transfusion practice in trauma patients. The determination of this review article is to update on current transfusion practices in trauma. A search of PubMed, Google Scholar, and bibliographies of published studies were conducted using a combination of key-words. Recent articles addressing the transfusion practises in trauma from 2000 to 2014 were identified and reviewed. Trauma induced consumption and dilution of clotting factors, acidosis and hypothermia in a severely injured patient commonly causes trauma-induced coagulopathy. Early infusion of blood products and early control of bleeding decreases trauma-induced coagulopathy. Hypothermia and dilutional coagulopathy are associated with infusion of large volumes of crystalloids. Hence, the predominant focus is on damage control resuscitation, which is a combination of permissive hypotension, haemorrhage control and haemostatic resuscitation. Massive transfusion protocols improve survival in severely injured patients. Early recognition that the patient will need massive blood transfusion will limit the use of crystalloids. Initially during resuscitation, fresh frozen plasma, packed red blood cells (PRBCs and platelets should be transfused in the ratio of 1:1:1 in severely injured patients. Fresh whole blood can be an alternative in patients who need a transfusion of 1:1:1 thawed plasma, PRBCs and platelets. Close monitoring of bleeding and point of care coagulation tests are employed, to allow goal-directed plasma, PRBCs and platelets transfusions, in order to decrease the risk of transfusion-related acute lung injury.

  18. Post-transfusion and maternal red blood cell alloimmunization in Uganda

    NARCIS (Netherlands)

    Natukunda, Bernard

    2013-01-01

    Over the last two decades, there has been substantial progress in the area of blood safety in Uganda. In contrast, little attention has been paid to transfusion safety in Uganda and there are gaps in laboratory and clinical transfusion practices within hospitals. Assessment of the current practice a

  19. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Institute of Scientific and Technical Information of China (English)

    Wu Changping; Deng Haifeng; Jiang Jingting

    2013-01-01

    Objective:To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK) cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods:Peripheral blood mononuclear cells (PBMC) in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ), recombinant human interleukin 1α (rhIL-1α), CD3 monoclonal antibody (CD3McAb) and recombinant human interleukin 2 (rhIL-2). Immunophenotypes were dynamically monitored by lfow cytometry (FCM), and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT) method. Results:After induction and expansion at different time, CD3+, CD3+CD8+and CD3+CD56+in mononuclear cells (MNC) had an up-regulated tendency. CD3+CD4+reached the peak on day 7, and then decreased slowly;CD25 reached the peak in earlier period of cultivation (3-7 days), and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR) was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was signiifcantly higher than that of non-activated PBMC, and the difference was statistically signiifcant (P Conclusion:PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  20. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Changping Wu

    2013-09-01

    Full Text Available Objective: To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods: Peripheral blood mononuclear cells (PBMC in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ, recombinant human interleukin 1α (rhIL- 1α, CD3 monoclonal antibody (CD3McAb and recombinant human interleukin 2 (rhIL-2. Immunophenotypes were dynamically monitored by flow cytometry (FCM, and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT method. Results: After induction and expansion at different time, CD3+, CD3+CD8+ and CD3+CD56+ in mononuclear cells (MNC had an up-regulated tendency. CD3+CD4+ reached the peak on day 7, and then decreased slowly; CD25 reached the peak in earlier period of cultivation (3-7 days, and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was significantly higher than that of non-activated PBMC, and the difference was statistically significant (P < 0.01. Conclusion: PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+ cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  1. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  2. Transfusion Medicine

    Directory of Open Access Journals (Sweden)

    Smit Sibinga CT

    2013-07-01

    Full Text Available Cees Th. Smit Sibinga ID Consulting, Zuidhorn, The NetherlandsTransfusion Medicine is a bridging science, spanning the evidence-based practice at the bedside with the social sciences in the community.     Transfusion Medicine starts at the bedside. Surprisingly, only recently that has become rediscovered with the development of ‘patient blood management’ and ‘patient centered’ approaches to allow the growth of an optimal and rational patient care through supportive hemotherapy – safe and effective, affordable and accessible.1    Where transfusion of blood found its origin in the need of a patient, it has drifted away for a long period of time from the bedside and has been dominated for almost a century by laboratory sciences. At least the first ten editions of the famous and well reputed textbook Mollison’s Blood Transfusion in Clinical Medicine contained only a fraction on the actual bedside practice of transfusion medicine and did not focus at all on patient blood management.2    This journal will focus on all aspects of the transfusion chain that immediately relate to the bedside practice and clinical use of blood and its components, and plasma derivatives as integral elements of a human transplant tissue. That includes legal and regulatory aspects, medical, ethical and cultural aspects, pure science and pathophysiology of disease and the impact of transfusion of blood, as well as aspects of the epidemiology of blood transfusion and clinical indications, and cost-effectiveness. Education through timely and continued transfer of up to date knowledge and the application of knowledge in clinical practice to develop and maintain clinical skills and competence, with the extension of current educational approaches through e-learning and accessible ‘apps’ will be given a prominent place.

  3. Quality of life and use of red cell transfusion in patients with myelodysplastic syndromes. A systematic review.

    Science.gov (United States)

    Pinchon, Deborah J; Stanworth, Simon J; Dorée, Carolyn; Brunskill, Susan; Norfolk, Derek R

    2009-10-01

    The main treatment for many patients with Myelodysplastic Syndromes (MDS) remains red cell transfusion to attenuate the symptoms of chronic anemia. Fatigue can reduce a patient's health related quality of life (HRQoL), but there is little understanding of the optimal use of transfusions to improve this. A systematic review was performed to identify and appraise publications reporting the use of HRQoL instruments in patients with MDS. A total of 17 separate studies were identified that used 14 HRQoL instruments, but only one MDS disease specific HRQoL instrument (QOL-E) was reported. Two well established HRQoL instruments were most often used in MDS research (variants of the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30)). Several common problems were identified in the published literature including a lack of power calculations to detect clinically relevant changes, small sample sizes and significant attrition rates for completion of HRQoL assessments, all of which limit the strength of any conclusions. There is no consensus on the optimal transfusion regimen to improve HRQoL in transfusion-dependent MDS. Future research into HRQoL within MDS is a pressing requirement. Studies should focus on the domains that are of most clinical importance to the patient as well as traditional quantitative changes of hemoglobin concentration. PMID:19705430

  4. Alloimmunization screening after transfusion of red blood cells in a prospective study Pesquisa de aloimunização após transfusão de concentrados de hemácias em um estudo prospectivo

    Directory of Open Access Journals (Sweden)

    Vitor Mendonça Alves

    2012-01-01

    Full Text Available BACKGROUND: Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients. OBJECTIVE: a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM, Brazil was performed to correlate alloimmunization to clinical and epidemiological data. METHODS: Blood samples of 143 patients with initial negative antibody screening were collected at intervals for up to 15 months after the transfusion of packed red blood cells. Samples were submitted to irregular antibody testing and, when positive, to the identification and serial titration of alloantibodies. The Fisher Exact test and Odds Ratio were employed to compare proportions. RESULTS: Fifteen (10.49% patients produced antibodies within six months of transfusion. However, for 60% of these individuals, the titers decreased and disappeared by 15 months after transfusion. Anti-K antibodies and alloantibodies against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K. There was an evident correlation with the number of transfusions. CONCLUSIONS: Given the high incidence of clinically important red blood cell alloantibodies in patients transfused in surgical and clinical emergency services, we suggest that phenotyping and pre-transfusion compatibilization for C, c, E, e (Rh system and K (Kell system antigens should be extended to all patients with programmed surgeries or acute clinical events that do not need emergency transfusions.OBJETIVO: Vários aloanticorpos irregulares antieritrocitários, produzidos por sensibilizações a antígenos estranhos durante gestações ou transfusões, possuem importância clínica por provocarem hemólise no feto ou recém-nascido e/ou no receptor de sangue. Diante

  5. Effect of irradiation and leukocyte filtration on red cell transfusion for premature infants in an incubator

    International Nuclear Information System (INIS)

    We investigated the effect of irradiation and leukocyte filtration on red cells in MAP solution (RC-MAP) for premature infants. RC-MAPs were stored for 3 or 7 days and pretreated with 15-Gy irradiation and a leukocyte depletion filter, with either the irradiation or filtration performed first. Infusion was performed using an infusion pump for 8 hr at a speed of 2 ml/hr through a 4 ml, 100 cm tube and a 24 G needle passing into an infant incubator warmed to 34degC. Free hemoglobin concentration in the supernatant of tested RC-MAP stored 7 days and irradiated after filtration was increased to the maximum level of 42.6 mg/dl. Potassium ion level in the supernatants and ATP and 2, 3-DPG concentration in red cells from tested RC-MAP were similar to pretreated values. Maximum potassium ion level was increased to 23.5 mEq/l. Our results showed that both irradiation and filtration against RC-MAP solutions stored for 3 or 7 days is safe for use with premature infants in warmed incubators. However, further investigation is necessary to clarify the risk of bacterial contamination in such transfusion situations. (author)

  6. Clinical significance of determination of changes of serum ferritin, MMP-2 and MMP-9 levels and after transfusion of red blood cells in patients with chronic nephritis

    International Nuclear Information System (INIS)

    Objective: To explore the changes of serum Ferritin, MMP-2 and MMP-9 contents after transfusion of red blood cells in patients with chronic nephritis. Methods: Serum Ferritin (with RIA) and serum MMP-2, MMP-9 (with ELISA) levels were measured in 32 patients with chronic nephritis both before and after a course of transfusion of red blood cells and 35 controls. Results: Before transfusion, the serum Ferritin, MMP-9 levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum Ferritin, MMP-2 and MMP-9 levels is clinically useful for management of patients with chronic nephritis. (authors)

  7. Prevalence and specificities of red cell alloantibodies in transfusion-dependent beta thalassemia patients in Yazd

    OpenAIRE

    Vaziri, M.; JavadzadehShahshahani, H; Moghaddam, M.; Taghvaee, N

    2015-01-01

    Background Multiple transfusions in thalassemia patients may lead to antibody production against blood group antigens and hemolytic transfusion reaction might occur. In this study, antibody screening test was performed by tube and gel methods to determine the prevalence and specificity of alloantibodies in thalassemia patients. Materials and Methods In this cross-sectional study, overall of 100 thalassemia patients from Yazd thalassemia clinic were recruited from July to September 2013. Two b...

  8. Geographic Variability in Potentially Discretionary Red Blood Cell Transfusions After Coronary Artery Bypass Grafting Surgery

    Science.gov (United States)

    Likosky, Donald S.; Al-Attar, Paul M.; Malenka, David J.; Furnary, Anthony P.; Lehr, Eric J.; Paone, Gaetano; Kommareddi, Mallika; Helm, Robert; Jin, Ruyun; Maynard, Chuck; Hanson, Eric C.; Olmstead, Elaine M.; Mackenzie, Todd A.; Ross, Cathy S.; Zhang, Min

    2016-01-01

    We assessed regional differences in potentially discretionary [coronary artery bypass (CABG) surgery. Regional variation in overall RBC rates remained after risk adjustment, perhaps due to differences in regional practice environments. Objective A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the “Cardiac Surgery Quality IMPROVEment (IMPROVE) Network”. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary [coronary artery bypass (CABG) surgery across 56 medical centers in four IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intra-operative practices, and percentage of cases receiving RBC transfusions were collected. Region-specific transfusion rates were calculated, after adjusting for pre- and intra-operative factors among region-specific centers. Results There were small, but significant, differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% (2,826/11,200) of CABG procedures. Significant variation in use and number of RBCs existed across regions [None: 74.8% (min:max 70.0%, 84.1%), 1 unit: 9.7% (5.1%, 11.8%), 2 units: 15.5% (9.1%, 18.2%)], p<0.001. Variation in overall transfusion rates remained after adjustment (9.1% – 31.7%, p<0.001). Conclusions Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates. PMID:25227699

  9. Severe hemolytic transfusion reaction due to anti-D in a D+ patient with sickle cell disease.

    Science.gov (United States)

    Ipe, Tina S; Wilkes, Jennifer J; Hartung, Helge D; Westhoff, Connie M; Chou, Stella T; Friedman, David F

    2015-03-01

    A 5-year-old male with sickle cell disease presented with pain, dark urine, and fatigue 10 days after a red blood cell (RBC) transfusion. Laboratory evaluation demonstrated severe anemia, blood type O+, and anti-D in the serum. Anti-D in a D+ patient led to RH genotyping, which revealed homozygosity for RHD*DAU4 that encodes partial D antigen. Anti-D in this patient whose RBCs exclusively express partial D caused a delayed hemolytic transfusion reaction after exposure to D+ RBCs. The finding of anti-D in a D+patient should be investigated by molecular methods to help distinguish an alloantibody from an autoantibody. PMID:25171447

  10. Solid Phase Red Cell Adherence Assay: a tubeless method for pretransfusion testing and other applications in transfusion science.

    Science.gov (United States)

    Ching, Eric

    2012-06-01

    Solid Phase Red Cell Adherence Assay (SPRCA) is one of the two tubeless methods developed to improve sensitivity and specificity in blood group serology. The SPRCA (solid phase) and the column agglutination (gel) technology have gained wide acceptance following successful adaptation to fully automated platforms, The purpose of this paper is to discuss the development, principle, procedures as well as laboratory and clinical applications of the SPRCA in transfusion medicine.

  11. Transfusão de hemácias em terapia intensiva: controvérsias entre evidências Red blood cell transfusion in the intensive care setting: controversies amongst evidence

    Directory of Open Access Journals (Sweden)

    Rubens Carmo Costa Filho

    2009-08-01

    com hemoglobina superiores a 7 g/dL. Não existe um consenso sobre o limiar transfusional em pacientes críticos. Os pacientes com doença cardiovascular parecem apresentar um maior risco de morte do que aqueles sem doença cardiovascular, para qualquer nível de hemoglobina. A transfusão guiada por níveis de hemoglobina e parâmetros fisiológicos, oxi-hemodinâmicos individualizados e contexto clínico parece ser atualmente estratégia mais aceita do que a correção arbitrária e isolada da hemoglobina.Anemia is a prevalent issue in intensive care units. It appears in the first days, and may continue or worsen during hospital stay. Its etiology is generally multifactorial. Red blood cell transfusion is the most common intervention for treating anemia. Approximately 12 million blood units are used for transfusions in the United States, 25% to 30% in the intensive care units. Due to reduction of transfusion infections the increased safety has allowed an expansion of clinical indications. However, transfusion therapy is associated with other adverse effects such as nosocomial infections, immunological impairment, lung injury, hemolytic reactions and higher cancer incidence. Various papers have tried to show an association between correction of anemia and mortality-morbidity, but no consensus has been reached in literature. One of the current World Health Organization's proposals is to reduce potentially unnecessary transfusions, promoting a rational transfusion attitude. The primary objective of this narrative review is to approach controversies regarding the transfusion threshold according to recent studies, and as a secondary objective, it aims to discuss iatrogenic anemia aspects and the different behaviors among intensivists on the best practices for implementation of transfusion practices. It is not within our objectives to discuss transfusion complications, although they are mentioned. A search was conducted on electronic literature databases (Pub

  12. Post-transfusion red cell alloimmunisation in patients with acute disorders and medical emergencies Aloimunização após transfusão de concentrado de hemácias em pacientes atendidos em um serviço de emergência

    OpenAIRE

    Francisco W. R. Santos; Silvia Maria M. Magalhães; Rosa Maria S. Mota; Maria Helena Pitombeira

    2007-01-01

    Alloimmunisation following red cell transfusion is a complication in patients with chronic diseases requiring multiple transfusions. The aim of this study was to determine the frequency of alloimmunisation, to identify involved alloantibodies, to establish risk factors and to quantify the alloimmunisation risk in patients with acute disorders who received red cell transfusion at the Instituto Dr. José Frota from January 1999 to January 2001. Of the 5,690 recipients who received 16,547 units o...

  13. Delayed Serological Transfusion Reaction After Platelet Transfusion Due to Anti-e.

    Science.gov (United States)

    Sachan, Deepti; Kumar, Aswin; Jothimani, Dinesh; Rela, Mohamed

    2016-06-01

    Delayed serological transfusion reaction (DSTR) is defined as absence of clinical signs of hemolysis and demonstration of new, clinically-significant antibodies against red blood cells after a transfusion, by either positive direct antiglobulin test or positive antibody screen with newly identified RBC alloantibody. Various delayed hemolytic transfusion reaction cases are reported after red cell transfusions. However, the incidence of DSTR after platelet transfusion due to non-Rh(D) antibodies is not much documented. We report here a case of DSTR due to anti-e Rh antibody in a multiply red cell alloimmunized female patient after single donor platelets transfusion. PMID:27408414

  14. Metabolomics in transfusion medicine.

    Science.gov (United States)

    Nemkov, Travis; Hansen, Kirk C; Dumont, Larry J; D'Alessandro, Angelo

    2016-04-01

    Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry-based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products. Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine-relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years. Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion-relevant variables, such as 24-hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions.

  15. Fluid shift from intravascular compartment during fetal red blood cell transfusion

    NARCIS (Netherlands)

    Kamping, M.A.; Pasman, S.A.; Bil-van den Brink, C.P.; Oepkes, D.; Adama van Scheltema, P.N.; Vandenbussche, F.P.H.A.

    2013-01-01

    OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal circulation by increasing volume and pressure, and a fluid shift from the fetal circulation occurs even during the procedure. The aim of this study was to quantify the intraprocedural fluid shift and to investigate the e

  16. [Organ transplantation and blood transfusion].

    Science.gov (United States)

    Matignon, M; Bonnefoy, F; Lang, P; Grimbert, P

    2011-04-01

    Pretransplant blood transfusion remains a controversial subject and its history can summarize the last 40 years of transplantation. Until 1971, transfusions were widely used in patients awaiting transplantation, especially due to the anemia induced by the chronic renal dysfunction. Then, a noxious effect of preformed anti-HLA antibodies on renal grafts survival was reported and pretransplant transfusions were stopped. Between 1972 and 1977, improvement of renal graft survival in patients who received pretransplant transfusions was noted. Therefore, from 1978 on, a systematic policy of pretransplant transfusions was adopted by almost all centres of transplantation. During the eighties, it was again abandoned for several reasons: absence of graft survival improvement in patients treated by cyclosporine, HLA immunization leading to an increased incidence of acute graft rejection, risk of viral diseases transmission and human recombinant erythropoietin development. The lack of improvement in graft survival for ten years has been leading the transplant community to look for antigen-specific immunosuppressive strategies to achieve transplantation tolerance. Donor-specific transfusion may have clinical benefits, as long-term grafts survival improvement, through modulation of the recipient's cellular immune system and has been recently reconsidered, especially before living donor transplantation. The immunological mechanisms inducing a tolerance-gaining effect of transfusions are still misunderstood, but the recent discovery of immunomodulatory effects of the apoptotic cells present in cellular products could enlighten our comprehension of pretransplant transfusions benefits and could help to develop specific tolerance induction strategies in solid organ transplantation. PMID:21398160

  17. Transfusion strategy

    DEFF Research Database (Denmark)

    Jakobsen, Carl-Johan

    2014-01-01

    Blood transfusion is associated with increased morbidity and mortality and numerous reports have emphasised the need for reduction. Following this there is increased attention to the concept of patient blood management. However, bleeding is relatively common following cardiac surgery and is furth....... In conclusion the evidence supports that each institution establishes its own patient blood management strategy to both conserve blood products and maximise outcome....

  18. Study on changes of serum ferritin (SF), folic acid (FA) and vitamin B12 levels after transfusion of preserved red cells (PRC) in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Objective: To explore the changes of serum SF, FA and VitB12 levels after transfusion of preserved red cells in patients with IDA. Methods: Serum SF, FA and VitB12 levels (with RIA) were detected both before and after transfusion of preserved red cells in 32 patients with IDA as well as in 35 controls. Results: Before transfusion of preserved red cells, the serum SF levels were significantly lower than those in controls (P12 levels were significantly higher (P12 were not much different from those in the controls. Conclusion: Transfusion of preserved red cells proves to be very useful. (authors)

  19. Types of Blood Transfusions

    Science.gov (United States)

    ... Home » Health Information for the Public » Health Topics » Blood Transfusion » Types of Blood Transfusions Explore Blood Transfusion What Is... ... Share this page from the NHLBI on Twitter. Types of Blood Transfusions Blood is transfused either as whole blood ( ...

  20. Blood transfusion is associated with increased resource utilisation, morbidity and mortality in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Scott Bharathi

    2008-01-01

    Full Text Available The purpose of the present investigation was to examine the impact of blood transfusion on resource utilisation, morbidity and mortality in patients undergoing coronary artery bypass graft (CABG surgery at a major university hospital. The resources we examined are time to extubation, intensive care unit length of stay (ICULOS and postoperative length of stay (PLOS. We further examined the impact of number of units of packed red blood cells (PRBCs transfused during PLOS. This is a retrospective observational study and includes 1746 consecutive male and female patients undergoing primary CABG (on- and off-pump at our institution. Of these, 1067 patients received blood transfusions, while 677 did not. The data regarding the demography, blood transfusion, resource utilisation, morbidity and mortality were collected from the records of patients undergoing CABG over a period of three years. The mean time to extubation following surgery was 8.0 h for the transfused group and 4.3 h for the nontransfused group ( P ≤ 0.001. The mean ICULOS for the transfused group was 1.6 d and 1.2 d for the nontransfused group ( P < 0.001. The PLOS was 7.2 d for the transfused group and 4.3 d for no-transfused cohorts ( P ≤ 0.001. In all patients and in patients with no preoperative morbidity, partial correlation coefficients were used to examine the effects of transfusion on mortality, time to extubation, ICULOS and PLOS. Linear regression model was used to assess the effect of number of PRBC units transfused on PLOS. We noted that PLOS increased with the number of PRBCs units transfused. Transfusion is significantly correlated with the increased time to extubation, ICULOS, PLOS and mortality. The transfused patients had significantly more postoperative complications than their nontransfused counterparts ( P ≤ 0.001. The 30-day hospital mortality was 3.1% for the transfused group with no deaths in the nontransfused group ( P ≤ 0.001. We conclude that the CABG

  1. Increased Mortality in Adult Trauma Patients Transfused with Blood Components Compared with Whole Blood

    OpenAIRE

    Jones, Allison R.; Frazier, Susan K

    2014-01-01

    Hemorrhage is a preventable cause of death among trauma patients, and management often includes transfusion, either whole blood or a combination of blood components (packed red blood cells, platelets, fresh frozen plasma). We used the 2009 National Trauma Data Bank to evaluate the relationship between transfusion type and mortality in adult major trauma patients (n = 1745). Logistic regression analysis identified three independent predictors of mortality: Injury Severity Score, emergency tran...

  2. Blood Transfusion and Donation

    Science.gov (United States)

    ... in the United States receive life-saving blood transfusions. During a transfusion, you receive whole blood or parts of blood ... liver failure or a severe infection. Most blood transfusions go very smoothly. Some infectious agents, such as ...

  3. Blood Transfusion (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Blood Transfusions KidsHealth > For Parents > Blood Transfusions Print A ... and help put your child at ease. About Blood Transfusions Blood is like the body's transportation system. ...

  4. Blood Transfusions (For Teens)

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Blood Transfusions KidsHealth > For Teens > Blood Transfusions Print A ... United States get blood transfusions. A Bit About Blood As blood moves throughout the body, it carries ...

  5. [Research advance on clinical blood transfusion and tumor therapy].

    Science.gov (United States)

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  6. Postoperative red blood cell transfusion strategy in frail anemic elderly with hip fracture. A randomized controlled trial.

    Science.gov (United States)

    Gregersen, Merete

    2016-04-01

    Hip fracture in the elderly is associated with poor recovery from physical disability and mortality. Perioperative blood loss is common, and anemia might be fatal in the frail elderly. Red blood cell transfusions might increase the risk of infection. In an observational study, a liberal transfusion strategy with hemoglobin (Hb) target of 7 mmol/l (11.3 g/dl) seemed to improve survival in nursing home residents with hip fracture compared to the recommended restrictive strategy with a Hb target of 6 mmol/l (9.7 g/dl) according to the Danish Health Authority. Our aim was to compare these two strategies in the frail elderly in a randomized controlled trial on the outcomes: recovery from physical disabilities, mortality, infection, infection biomarkers, and overall Quality of Life (OQoL). We included 284 elderly admitted to hospital for surgical hip fracture repair from nursing homes or sheltered housing facilities. The anemic patients were assigned postoperatively to the liberal or the restrictive transfusion strategy. Randomization divided each transfusion group into two equal blocks with regard to type of the residence. Hb was measured daily during the first three postoperative days, at least once during the following 4-6 days, then at least once a week during the subsequent three weeks. The transfusions were administered according to group assignments, but no later than 24 hours after the Hb determination, one unit at a time, and no more than two units per day. The intervention lasted for 30 days after surgery. Outcome measurements were performed on days 10, 30, 90, and 365. Blinded assessors evaluated physical performance and OQoL. The liberal transfusion strategy did not improve recovery from physical disabilities, mortality, infection rate, or OQoL compared to the restrictive strategy. However, in nursing home residents, 90-day mortality rate (20%) following the liberal strategy was statistically significantly lower than that (36%) after the restrictive strategy

  7. Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies.

    Science.gov (United States)

    Ferrandiz, I; Congy-Jolivet, N; Del Bello, A; Debiol, B; Trébern-Launay, K; Esposito, L; Milongo, D; Dörr, G; Rostaing, L; Kamar, N

    2016-09-01

    Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non-HLA-sensitized patients who had received an ABO-compatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation but not for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients.

  8. Transfusion associated circulatory overload

    Directory of Open Access Journals (Sweden)

    Naveen Agnihotri

    2014-01-01

    Full Text Available Transfusion associated circulatory overload (TACO is an established, but grossly under diagnosed and underreported complication of blood transfusion. We present the case of a 46-year-old diabetic and hypertensive patient admitted to our hospital for recurrent episodes of urinary retention. Over initial 3 days of the admission, the patient received multiple units of packed red blood cells (RBC and fresh frozen plasma, uneventfully. However, the patient developed signs and symptoms suggestive of TACO with only small amount of the 4 th unit of RBC. The patient had to be shifted to the Intensive Care Unit for further management of this complication. Etiology of TACO is more complex than a mere circulatory overload and is still not completely understood. TACO leads to a prolonged hospital stay and morbidity in the patients developing this complication. TACO thus needs to be suspected in patients at risk for this complication.

  9. Efeito da transfusão de concentrado de hemácias sobre parâmetros de inflamação e estresse oxidativo em pacientes criticamente enfermos Effect of red blood cell transfusion on parameters of inflammation and oxidative stress in critically ill patients

    Directory of Open Access Journals (Sweden)

    Samuel Diomário da Rosa

    2011-03-01

    Full Text Available INTRODUÇÃO: Transfusão de concentrado de hemácias é freqüentemente prescrita nas unidades de terapia intensiva. Durante muito tempo a transfusão de hemácias era vista como tendo benefícios clínicos óbvios. Entretanto nos últimos anos a prática de transfusão sanguínea tem sido examinada de uma forma mais cautelosa, levando a investigações a respeito dos benefícios transfusionais, incluindo aqui o fato de os efeitos imunomoduladores relacionados à transfusão podem aumentar o risco de morbimortalidade dos pacientes. OBJETIVOS: Avaliar o efeito da transfusão de concentrado de hemácias e sua relação com a produção de citocinas inflamatórias e dano oxidativo em pacientes criticamente enfermos admitidos em uma unidade de terapia intensiva. MÉTODOS: Foram analisados durante 6 meses, no ano de 2008, pacientes internados na unidade de terapia intenvia que realizaram transfusão de concentrado de hemácias. Foram analisados os níveis séricos pré e pós transfusionais de interleucina-6 (IL-6, proteínas carboniladas e substâncias reativas ao ácido tiobarbitúrico (TBARS. RESULTADOS: Houve diminuição dos níveis séricos de IL-6 pós-transfusionais e um aumento significativo tanto para TBARS quanto para proteínas carboniladas. No entanto não houve significância estatística entre os níveis séricos de IL-6, TBARS antes e após transfusão de concentrado de hemácias e a taxa de mortalidade. Contudo ocorreu significância da relação dos níveis pós transfusionais de proteínas carboniladas e mortalidade. CONCLUSÃO: Transfusão de concentrado de hemácias é associada a aumento dos marcadores de dano oxidativo e diminuição de IL-6 em pacientes criticamente enfermos.INTRODUCTION: Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been

  10. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    OpenAIRE

    Kirtan Nautiyal; Rui Li; Sarvari Yellapragada; Perumal Thiagarajan; Martha Mims; Gustavo Rivero

    2014-01-01

    Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS) who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD) and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA) therapy, who attained transfusion and gro...

  11. Retinopathy of Prematurity and Blood Transfusion Protocols

    OpenAIRE

    P Mohagheghi; Khosravi, N.; H Samaii

    2003-01-01

    To determine the role of blood transfusion protocols on retinopathy of prematurity (ROP), a prospective cohort study on 57 premature infants under 1501 grams birth weight was performed. Fourteen day-old infants were divided into two groups randomly. Infants in group 1 (n=27) received packed red blood cell transfusion only if specific medical signs were met and their hematocrit level was under 30%. Infants in group 2 (n=30) received blood transfusion to maintain their hematocrit level > 40%...

  12. Acute pain transfusion reaction.

    Science.gov (United States)

    Hardwick, Jody; Osswald, Michael; Walker, Daniel

    2013-11-01

    A 34-year-old woman with a diagnosis of hemophagocytic lymphohistocytosis (HLH) received a double umbilical cord blood transplantation following a myeloablative chemotherapy preparative regimen with busulfan and cyclophosphamide. HLH is a rare, potentially fatal hematologic disorder characterized by the overactivation of histocytes and T lymphocytes, leading to organ infiltration and acute illness. On day 25 post-transplantation, the patient required a platelet transfusion for a platelet count of 6,000 per ml (normal range = 150,000-450,000 per ml). The patient's blood type prior to the cord blood transplantation was B positive and, although both umbilical cord blood donors were O positive, the patient was still B positive per blood bank testing on that day. Although the recipient of an allogenic stem cell transplantation will eventually become the blood type of the donor, the time for this process to occur varies for each person. That process must be monitored by the blood bank for the purpose of cross-matching blood products to decrease hemolysis as much as possible. The patient was premedicated with the facility's standard for platelet transfusions: acetaminophen 650 mg and diphenhydramine 25 mg about 30 minutes prior to the platelet transfusion. PMID:24161631

  13. Longitudinal MRI and Ferritin Monitoring of Iron Overload in Chronically Transfused and Chelated Children With Sickle Cell Anemia and Thalassemia Major.

    Science.gov (United States)

    Aubart, Mélodie; Ou, Phalla; Elie, Caroline; Canniffe, Carla; Kutty, Shelby; Delos, Vincent; Graffigne, Christine; de Montalembert, Mariane; Brousse, Valentine

    2016-10-01

    Iron overload is an ineluctable complication in chronically transfused children warranting accurate assessment to avoid related morbidity. We investigated longitudinally the relationships between ferritin levels and hepatic and cardiac T2* magnetic resonance imaging (MRI) in a cohort of chronically transfused children receiving chelation therapy. Thirty children with sickle cell anemia (SCA) and 7 with thalassemia major (TM) chelated similarly by deferasirox were analyzed. Sex ratio, age, median duration of transfusion programs (5 y; range, 2 to 14 y), median transfusion iron intake 0.54 mg/kg/d (range, 0.27 to 0.74 mg/kg/d), and median ferritin level (1550 mg/L; range, 184 to 6204 mg/L) were comparable in TM and SCA. A significant relation was found between ferritin level and transfusion iron intake (P<0.001) despite chelation therapy. Analysis of 73 hepatic T2* MRI performed yearly demonstrated severe hepatic iron overload (≥14 mg/g) in 38.3% cases and a strong relationship between serum ferritin level and liver iron content both in SCA and TM (P<0.001). Analysis of 55 cardiac T2* MRI measurements found no cardiac overload in patients with SCA. Cardiac iron overload was moderate in 4 cases and severe in 1 case of TM. In almost half the cases, ferritin trend correctly predicted hepatic iron trend, both in patients with SCA and TM but failed to predict cardiac iron trend, notably in TM patients. Despite chelation therapy, iron burden in chronically transfused patients remains a threat. Ferritin levels are associated with liver iron overload in chelated children with SCA and TM, but iron burden should be best monitored with MRI whenever the setting allows it. PMID:27548334

  14. Transfusão de sangue em terapia intensiva: um estudo epidemiológico observacional Blood transfusion in intensive care: an epidemiological observational study

    Directory of Open Access Journals (Sweden)

    José Rodolfo Rocco

    2006-09-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A transfusão de concentrado de hemácias (CHA é muito freqüente no centro de tratamento intensivo (CTI, mas as conseqüências da anemia nos pacientes gravemente enfermos ainda são obscuras. Os objetivos desse estudo foram avaliar a freqüência, as indicações, os limiares transfusionais e o prognóstico dos pacientes criticamente enfermos que receberam CHA. MÉTODO: Estudo prospectivo de coorte realizado no CTI médico-cirúrgico de um Hospital Universitário durante 16 meses. Foram coletados dados demográficos, clínicos e os relacionados a transfusão de CHA. Regressão logística binária foi utilizada após as análises univariadas. RESULTADOS: Dos 698 pacientes internados, 244 (35% foram transfundidos com CHA. Os pacientes clínicos e em pós-operatório de urgência foram mais transfundidos. Os limiares transfusionais foram: hematócrito = 22,8% ± 4,5% e hemoglobina = 7,9 ± 1,4 g/dL. Os pacientes transfundidos receberam em média 4,4 ± 3,7 CHA e apresentaram maior letalidade no CTI (39,8% versus 13,2%; p 5 unidades e escore SAPS II. CONCLUSÕES: A transfusão de CHA é freqüente no CTI, particularmente nos pacientes internados por problemas clínicos e após cirurgias de emergência, com internação prolongada, em VM e com cirrose hepática. O limiar transfusional observado foi mais baixo que aquele assinalado pela literatura. A transfusão de CHA foi associada com maior letalidade.BACKGROUND AND OBJECTIVES: Packed red blood cell (PRBC transfusion is frequent in intensive care unit (ICU. However, the consequences of anemia in ICU patients are poorly understood. Our aim was to evaluate the prevalence, indications, pre-transfusion hematocrit and hemoglobin levels, and outcomes of ICU patients transfused with PRBC. METHODS: Prospective cohort study conducted at a medical-surgical ICU of a teaching hospital during a 16-month period. Patients' demographic, clinical, laboratory and transfusion-related data

  15. Cancer incidence in blood transfusion recipients

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Edgren, Gustaf; Rostgaard, Klaus;

    2007-01-01

    , the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion. CONCLUSIONS: The marked increase in cancer risk shortly after a blood transfusion may......BACKGROUND: Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. METHODS: We used computerized files from Scandinavian...... blood banks to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios...

  16. Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.

    Directory of Open Access Journals (Sweden)

    Eva Maria Weissinger

    2015-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-HSCT is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI. The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors or on day +42 (haploidentical donors.Nine patients were included in the first trial (MHH; 2002 until 2007 2 were included in TK007 (2005-2009 and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI grade II, which was successfully controlled by ganciclovir (GCV. Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI are alive and well to date.

  17. Novel web-based real-time dashboard to optimize recycling and use of red cell units at a large multi-site transfusion service

    OpenAIRE

    Christopher Sharpe; Quinn, Jason G; Stephanie Watson; Donald Doiron; Bryan Crocker; Calvino Cheng

    2014-01-01

    Background: Effective blood inventory management reduces outdates of blood products. Multiple strategies have been employed to reduce the rate of red blood cell (RBC) unit outdate. We designed an automated real-time web-based dashboard interfaced with our laboratory information system to effectively recycle red cell units. The objective of our approach is to decrease RBC outdate rates within our transfusion service. Methods: The dashboard was deployed in August 2011 and is accessed by a short...

  18. Transfusion of blood and blood products: indications and complications.

    Science.gov (United States)

    Sharma, Sanjeev; Sharma, Poonam; Tyler, Lisa N

    2011-03-15

    Red blood cell transfusions are used to treat hemorrhage and to improve oxygen delivery to tissues. Transfusion of red blood cells should be based on the patient's clinical condition. Indications for transfusion include symptomatic anemia (causing shortness of breath, dizziness, congestive heart failure, and decreased exercise tolerance), acute sickle cell crisis, and acute blood loss of more than 30 percent of blood volume. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Platelet transfusion is indicated to prevent hemorrhage in patients with thrombocytopenia or platelet function defects. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy. Transfusion-related infections are less common than noninfectious complications. All noninfectious complications of transfusion are classified as noninfectious serious hazards of transfusion. Acute complications occur within minutes to 24 hours of the transfusion, whereas delayed complications may develop days, months, or even years later.

  19. Anemia and Blood Transfusion in Patients with Isolated Traumatic Brain Injury

    Science.gov (United States)

    Al-Dorzi, Hasan M.; Al-Humaid, Waleed; Tamim, Hani M.; Haddad, Samir; Aljabbary, Ahmad; Arifi, Abdulaziz; Arabi, Yaseen M.

    2015-01-01

    Rationale. By reducing cerebral oxygen delivery, anemia may aggravate traumatic brain injury (TBI) secondary insult. This study evaluated the impact of anemia and blood transfusion on TBI outcomes. Methods. This was a retrospective cohort study of adult patients with isolated TBI at a tertiary-care intensive care unit from 1/1/2000 to 31/12/2011. Daily hemoglobin level and packed red blood cell (PRBC) transfusion were recorded. Patients with hemoglobin < 10 g/dL during ICU stay (anemic group) were compared with other patients. Results. Anemia was present on admission in two (2%) patients and developed in 48% during the first week with hemoglobin < 7 g/dL occurring in 3.0%. Anemic patients had higher admission Injury Severity Score and underwent more craniotomy (50% versus 13%, p < 0.001). Forty percent of them received PRBC transfusion (2.8 ± 1.5 units per patient, median pretransfusion hemoglobin = 8.8 g/dL). Higher hospital mortality was associated with anemia (25% versus 6% for nonanemic patients, p = 0.01) and PRBC transfusion (38% versus 9% for nontransfused patients, p = 0.003). On multivariate analysis, only PRBC transfusion independently predicted hospital mortality (odds ratio: 6.8; 95% confidence interval: 1.1–42.3). Conclusions. Anemia occurred frequently after isolated TBI, but only PRBC transfusion independently predicted mortality. PMID:26605080

  20. Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2011-12-01

    Full Text Available The prevalence of fatal hemolytic transfusion reactions (HTRs is approximately 1:200000 per unit. Acute HTRs occur during or within 24 h after administration of a blood product. Transfusion of incompatible red blood cells (RBCs, and, more rarely, of a large volume of incompatible plasma usually are the causative agents. Delayed HTRs are caused by a secondary immune response to an antigen on the donor’s RBCs. Different mechanisms lead to intra- and extravascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell to cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways. Formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis result in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In this review, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given. (Journal of Current Pediatrics 2011; 9: 127-32

  1. Case report: massive postpartum transfusion of Jr(a+) red cells in the presence of anti-Jra.

    Science.gov (United States)

    Yuan, S; Armour, R; Reid, A; Abdel-Rahman, K F; Rumsey, D M; Phillips, M; Nester, T

    2005-01-01

    Jr(a) is a high-prevalence antigen. The rare Jr(a-) individuals can form anti-Jr(a) after exposure to the Jr(a) antigen through transfusion or pregnancy. The clinical significance of anti-Jr(a) is not well established. This study reports a case of a 31-year-old woman with a previously identified anti-Jr(a) who required massive transfusion of RBCs after developing life-threatening postpartum disseminated intravascular coagulopathy. Despite the emergent transfusion of 15 units of Jr(a) untested RBCs, she did not develop laboratory or clinical evidence of acute hemolysis. The patient's anti-Jr(a) had a pretransfusion titer of 4 and a monocyte monolayer assay (MMA) reactivity of 68.5% (reactivity > 5% is considered capable of shortening the survival of incompatible RBCs). The titer increased fourfold to 64 and the MMA reactivity was 72.5% on Day 10 posttransfusion. Review of laboratory data showed evidence of a mild delayed hemolytic transfusion reaction by Day 10 posttransfusion. Despite rare reports of hemolytic transfusion reactions due to anti-Jr(a) in the literature, most cases, including this one, report that this antibody is clinically insignificant or causes only mild delayed hemolysis. Clinicians should be advised to balance the risks of withholding transfusion with the small chance of significant hemolysis after transfusion of Jr(a+) RBCs in the presence of anti-Jr(a).

  2. Intraoperative transfusion of packed red blood cells in microvascular free tissue transfer patients: assessment of 30-day morbidity using the NSQIP dataset.

    Science.gov (United States)

    Kim, Bobby D; Ver Halen, Jon P; Mlodinow, Alexei S; Kim, John Y S

    2014-02-01

    Although often a life-saving therapeutic maneuver, there is minimal data available that details the effects of intraoperative packed red blood cell transfusion (IOT) after microvascular free tissue transfer. The National Surgical Quality Improvement Program database was queried to identify all patients who underwent microvascular free tissue transfer between 2006 and 2010. Multivariate logistic regression models were used to determine the association between intraoperative transfusion and outcomes. Upon bivariate and multivariate analyses, IOT was significantly associated with higher rates of overall complications (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.12-3.63), medical complications (OR, 3.35; 95% CI, 1.75-6.42), postoperative transfusion (OR, 6.02; 95% CI, 2.02-17.97), and reoperation (OR, 2.24; 95% CI, 1.24-4.04). IOT was not associated with either surgical complications or free flap loss. IOT significantly increases risk for adverse overall and medical complications. However, IOT was not associated with surgical complications or free flap loss. Transfusion practices in the operating room should be reevaluated to improve overall outcomes. PMID:24114710

  3. Intraoperative transfusion of packed red blood cells in microvascular free tissue transfer patients: assessment of 30-day morbidity using the NSQIP dataset.

    Science.gov (United States)

    Kim, Bobby D; Ver Halen, Jon P; Mlodinow, Alexei S; Kim, John Y S

    2014-02-01

    Although often a life-saving therapeutic maneuver, there is minimal data available that details the effects of intraoperative packed red blood cell transfusion (IOT) after microvascular free tissue transfer. The National Surgical Quality Improvement Program database was queried to identify all patients who underwent microvascular free tissue transfer between 2006 and 2010. Multivariate logistic regression models were used to determine the association between intraoperative transfusion and outcomes. Upon bivariate and multivariate analyses, IOT was significantly associated with higher rates of overall complications (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.12-3.63), medical complications (OR, 3.35; 95% CI, 1.75-6.42), postoperative transfusion (OR, 6.02; 95% CI, 2.02-17.97), and reoperation (OR, 2.24; 95% CI, 1.24-4.04). IOT was not associated with either surgical complications or free flap loss. IOT significantly increases risk for adverse overall and medical complications. However, IOT was not associated with surgical complications or free flap loss. Transfusion practices in the operating room should be reevaluated to improve overall outcomes.

  4. Epidemiology of massive transfusion

    DEFF Research Database (Denmark)

    Halmin, M A; Chiesa, F; Vasan, S K;

    2015-01-01

    Background: In recent years, massive transfusion protocols have received increasing attention. The potential risks associated with massive transfusion have been discussed and associations with both increased morbidity and mortality have been reported. However there is a paucity of comprehensive d...

  5. Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study

    Directory of Open Access Journals (Sweden)

    Gonzalez Marco

    2006-07-01

    Full Text Available Abstract Background Anemic syndrome is a frequent problem in intensive care units. The most probable etiology is the suppression of the erythropoietin response due to the direct effects of cytokines, as well as frequent blood sampling. Transfusions are not free of complications, therefore transfusion reactions are estimated to occur in 2% of the total packed red blood cells (pRBCs transfused. In the past several years, several trials had tried to compare the restrictive with the more liberal use of transfusions, and they were found to be equally effective. Nosocomial pneumonia is the most common nosocomial infection in intensive care units; the prevalence is 47% with an attributive mortality of 33%. There are multiple risk factors for the development of nosocomial pneumonia. Colonization of the upper airways is the most important pathophysiological factor but there are other factors implicated like, sedation techniques, inappropriate use of antibiotics and recumbent positioning. A secondary analysis of the CRIT study describes transfusion therapy and its practices in the United States. They found that transfusion practice is an independent risk factor for the development of nosocomial pneumonia. Methods This is a multicenter, prospective cohort study in different intensive care units in Colombia. A total of 474 patients were selected who had more than 48 hours of mechanical ventilation. The primary objective is to try to demonstrate the hypothetical relationship between the use of transfusions and nosocomial pneumonia. Secondly, we will try to determine which other factors are implicated in the development of pneumonia in intensive care units and describe the incidence of pneumonia and transfusion practices. Discussion Ventilator associated pneumonia is a primary problem in the intensive care unit, multiple factors have been associated with its presence in this study we try to explore the possible association between pneumonia and transfusion

  6. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus;

    2008-01-01

    BACKGROUND: Long-term survival of transfusion recipients has rarely been studied. This study examines short- and long-term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population. STUDY DESIGN AND METHODS: Population-based cohort study...... of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... registered transfusion. Three months after the first transfusion, 84.3 percent of recipients were alive. One-, 5-, and 20-year posttransfusion survival was 73.7, 53.4, and 27.0 percent, respectively. Survival was slightly poorer in men than in women, decreased with increasing age, and was worst...

  7. Liver Transplantation without Perioperative Transfusions Single-Center Experience Showing Better Early Outcome and Shorter Hospital Stay

    Directory of Open Access Journals (Sweden)

    Nicolás Goldaracena

    2013-01-01

    Full Text Available Background. Significant amounts of red blood cells (RBCs transfusions are associated with poor outcome after liver transplantation (LT. We report our series of LT without perioperative RBC (P-RBC transfusions to evaluate its influence on early and long-term outcomes following LT. Methods. A consecutive series of LT between 2006 and 2011 was analyzed. P-RBC transfusion was defined as one or more RBC units administrated during or ≤48 hours after LT. We divided the cohort in “No-Transfusion” and “Yes-Transfusion.” Preoperative status, graft quality, and intra- and postoperative variables were compared to assess P-RBC transfusion risk factors and postoperative outcome. Results. LT was performed in 127 patients (“No-Transfusion” = 39 versus “Yes-Transfusion” = 88. While median MELD was significantly higher in Yes-Transfusion (11 versus 21; P=0.0001 group, platelet count, prothrombin time, and hemoglobin were significantly lower. On multivariate analysis, the unique independent risk factor associated with P-RBC transfusions was preoperative hemoglobin (P<0.001. Incidence of postoperative bacterial infections (10 versus 27%; P=0.03, median ICU (2 versus 3 days; P=0.03, and hospital stay (7.5 versus 9 days; P=0.01 were negatively influenced by P-RBC transfusions. However, 30-day mortality (10 versus 15% and one- (86 versus 70% and 3-year (77 versus 66% survival were equivalent in both groups. Conclusions. Recipient MELD score was not a predictive factor for P-RBC transfusion. Patients requiring P-RBC transfusions had worse postoperative outcome. Therefore, maximum efforts must be focused on improving hemoglobin levels during waiting list time to prevent using P-RBC in LT recipients.

  8. Monitoração e avaliação clínica da eficácia da transfusão de sangue total e concentrado de hemácias em cães Monitoring and evaluation of the efficacy of whole blood and packed red cells transfusion in dogs

    Directory of Open Access Journals (Sweden)

    Marcel K. Morikawa

    2010-08-01

    Full Text Available A terapia transfusional tem grande potencial de salvar vidas na clínica de pequenos animais, e é usada principalmente na terapêutica de emergência em animais anêmicos, entretanto este procedimento está associado a vários riscos. Uma das formas de minimizá-los é pela monitoração constante durante a transfusão sanguínea, permitindo assim avaliar a melhora clínica do paciente. O objetivo deste trabalho foi avaliar a eficácia da transfusão de sangue total e de concentrado de hemácias em cães anêmicos, por meio da monitoração dos parâmetros vitais. Foram avaliadas 77 transfusões em cães, sendo 52 de sangue total armazenado e 25 de concentrado de hemácias. Durante todo o procedimento aferiu-se (a cada 15-30 minutos a temperatura, frequência cardíaca, frequência respiratória e a coloração de mucosas dos pacientes, além do tempo de preenchimento capilar. Os resultados obtidos mostraram que ambos os componentes promoveram melhora dos parâmetros avaliados a partir de 45 minutos do início da transfusão sanguínea, principalmente da frequência cardíaca, coloração de mucosas e tempo de preenchimento capilar (pTransfusion therapy has a great potential to save lives in small animals practice, and it has been used mainly in the emergency treatment for anemic animals, although this procedure is related to certain risks. A manner to minimize these risks is through keeping close monitoring during the time of transfusion, which furthermore allows an evaluation of recovering of the patient. The aim of the present research was to evaluate the efficacy of whole blood and packed red cells transfusions in anemic dogs. Seventy-seven transfusions in dogs have been done, 52 of whole blood and 25 of packed red cells, measuring (every 15-30 minutes temperature, cardiac and breathing frequency, mucous tissue color and capillaries filling time throughout the procedure. The outcome shows that both compounds, may cause improvements to every

  9. Red cell alloimmunization and infectious marker status (human immunodeficiency virus, hepatitis B virus and hepatitis C virus in multiply transfused thalassemia patients of North India

    Directory of Open Access Journals (Sweden)

    Raj Nath Makroo

    2013-01-01

    Full Text Available Background: Patients with thalassemia major are largely transfusion dependent and are thus exposed to a variety of risks such as transmission of infectious diseases, iron overload and alloimmunization. This study was performed to determine the prevalence of human immune deficiency virus (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV and red cell antibodies among multiple-transfused thalassemic patients in and around the national capital region. Materials and Methods: The Department of Transfusion Medicine, Indraprastha Apollo Hospitals, conducted this study in collaboration with the National Thalassemia Welfare Society over a period of 1 year starting February2011. Blood samples from the patients were tested for blood group, red cell alloantibody/ies, anti-HIV, anti-HCV and hepatitis B surface antigen (HBsAg by ELISA and for the respective viral ribonucleic acid (RNA or deoxyribonucleic acid (DNA by nucleic acid testing (NAT. Results: A total of 462 thalassemics which consists of 290 males and 172 females were tested. The overall alloimmunization rate was 4.1% and anti-Kell was the most common antibody identified. Thirteen cases (2.8% were positive for HBsAg by ELISA, 107 (23.1% were reactive for anti HCV and 11 (2.38% for anti HIV antibodies. Further screening and discriminatory assays by NAT confirmed the presence of HBV DNA in 11 cases, HIV RNA in 7 cases and HCV RNA in 48 cases. Conclusion: In spite of advances in Immunohematology and infectious marker testing in recent years, the rates of alloimmunization and infectious marker positivity remains high among multiply transfused patients like thalassemics. Provision of safe and adequate blood supply to these patients is a key to improving their quality-of-life and longevity.

  10. Rare and transient anti-D antibody response in D(-) liver transplant recipients transfused with D(+) red blood cells.

    Science.gov (United States)

    Burin des Roziers, N; Ibanez, C; Samuel, D; Francoz, C; Idri, S; François, A; Mortelecque, R; Bierling, P; Pirenne, F

    2016-07-01

    A retrospective analysis was conducted on 20 D(-) liver transplant (LT) recipients transfused with D(+) RBCs perioperatively and screened for RBC antibodies between 2 and 6 months later. None developed anti-D detectable by the indirect antiglobulin test. Two patients produced weak anti-D that reacted only with papain-treated RBCs at 10 and 11 days without any sign of immune haemolysis. Antibodies became quickly undetectable. These data suggest an unusual pattern of alloimmunization in LT recipients with rapid, weak and transient antibody response and support the safety of transfusing D(+) RBCs in most of D(-) patients during LT surgery. PMID:26918570

  11. Measuring the impact of a restrictive transfusion guideline in patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Hoeg, R T; Leinoe, E B; Andersen, P;

    2013-01-01

    Interventions to change physician transfusion behavior are often evaluated by examining the amount of red blood cell (RBC) units transfused or the proportion of patients transfused before and after the intervention. The pre-transfusion haemoglobin concentration is a sensitive measure of transfusi...

  12. Net haemoglobin increase from reinfusion of refrigerated vs. frozen red blood cells after autologous blood transfusions

    DEFF Research Database (Denmark)

    Ashenden, M; Mørkeberg, Jakob Sehested

    2011-01-01

    freezing. Nevertheless, frozen storage allowed haemoglobin to fully recover before reinfusion, while the haemoglobin was 10% lower in the refrigerated group compared with baseline. After reinfusion, the haemoglobin levels were 11·5% higher than the baseline values in the group reinfused with frozen blood......BACKGROUND AND OBJECTIVES  Two main blood storage procedures can be used for storing red blood cells: refrigeration and freezing. Nevertheless, the efficiency of these procedures measured as the increase in haemoglobin after reinfusion compared with baseline has never been examined. The main...... objective was to examine which storage procedure yielded the largest increase in circulating haemoglobin after reinfusion compared to baseline. MATERIALS AND METHODS  Equal volumes of blood from 15 men were withdrawn and stored either frozen or refrigerated as packed red blood cells. Serial measures...

  13. Proven and potential clinical benefits of washing red blood cells before transfusion: current perspectives

    OpenAIRE

    Schmidt, Amy; Refaai,Majed; Kirkley, Scott; Blumberg, Neil

    2016-01-01

    Amy E Schmidt, Majed A Refaai, Scott A Kirkley, Neil Blumberg Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA Abstract: Red blood cells (RBCs) are washed for a variety of reasons such as to remove excess potassium, cytokines, and other allergen proteins from the supernatant and/or to mitigate the effects of the storage lesion. The storage lesion is a product of RBC aging and include leakage of potassium and...

  14. Patient inclusion in transfusion medicine: current perspectives

    Directory of Open Access Journals (Sweden)

    Friedman MT

    2015-01-01

    blood transfusions via measures such as preoperative anemia management, intraoperative cell salvage, and improved transfusion guidelines. PBM strategies also focus on enhanced requirements for transfusion education and shared decision making, including informed consent and, thus, promote a patient-centered approach as defined by the Institute of Medicine. Keywords: informed consent, patient blood management, patient-centered approach, patient communication, shared decision making

  15. Application of DNA-based forensic analysis for the detection of homologous transfusion of whole blood and of red blood cell concentrates in doping control.

    Science.gov (United States)

    Stampella, Alessandra; Di Marco, Sabrina; Pirri, Daniela; de la Torre, Xavier; Botrè, Francesco; Donati, Francesco

    2016-08-01

    In this work we present the application of a method for the identification of homologous blood transfusions using forensic genetic techniques based on DNA typing. Ex vivo mixtures of human blood samples - either whole blood or red blood cell concentrates - simulating homologous blood transfusions at different percentages of the donor were typed for a panel of 16 highly variable DNA short tandem repeats (STR). Tested samples included also mixtures, which gave false-negative results if assayed by the reference flow cytofluorimetric method, which is based on the recognition of target antigens located on the membrane of the red blood cell. The recognition of triplets and quadruplets at various loci gave information of the presence of cells belonging to different individuals, as it is the case for homologous blood transfusions. Specificity and sensitivity of the method were assessed in the validation study. The method proved to be unequivocally specific since it was able to recognize all single profiles of each individual, clearly discriminating them from mixtures. Sensitivity resulted as a consequence of the percentage of the donor aliquot in the total volume of the mixture. Although the source of DNA in a blood sample is represented only by nucleated white blood cells, the same procedure resulted effective also in detecting mixtures of red blood cell concentrates (RBCC) from leukodepletion procedure: DNA of the donor from the residual white blood cells resulted still detectable, even if with an expected loss of sensitivity. The proposed approach may contribute to reduce the risk of false-negative results, which may occur using the reference cytofluorimetric method. PMID:27175858

  16. Importância dos carreadores de oxigênio livre de células Oxygen carriers free of cells in transfusion medicine

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Z. Novaretti

    2007-12-01

    Full Text Available Os procedimentos necessários para redução de efeitos adversos associados à transfusão de sangue, em especial aqueles decorrentes da transmissão de agentes infecciosos e da aloimunização leucócito-mediada têm impacto nos custos de produção de hemocomponentes. Paralelamente, as necessidades transfusionais têm aumentado globalmente, ficando evidente a necessidade de um substituto seguro e amplamente disponível para o sangue, chamado de sangue artificial ou de substituto do sangue. Visto que o seu desenvolvimento tem se concentrado na função de carrear oxigênio aos tecidos, daí utilizarmos, nesse texto, a denominação "Carreadores de oxigênio livre de células". Atualmente, dois tipos de carreadores de oxigênio livre de células têm sido testados: as soluções de hemoglobina modificadas (de origem humana ou bovina e os perfluorocarbonos (PFCs. Entretanto, esses produtos não são isentos de efeitos adversos e um grande número de pesquisas clínicas está em andamento para testar sua eficácia e segurança. O maior conhecimento desses carreadores de oxigênio livre de células e seus mecanismos de ação permitiu que aplicações outras, até mesmo não clínicas, estivessem em teste com as novas gerações desses produtos, expandindo assim as fronteiras da medicina transfusional.The procedures needed to reduce transfusion-associated adverse effects, especially those related to transfusion-transmitted diseases and leukocyte-mediated alloimmunization, have a great impact on the production cost of blood components. Additionally, blood transfusion has increased worldwide making the need for a safe substitute for blood evident. These products have been named artificial blood or blood substitutes. Based on the fact that their focus has been oxygen delivery to tissues, "free oxygen carrying cells" is more appropriate. Two major groups of free oxygen carring cells have been tested: modified hemoglobin solutions (bovine or human and

  17. How often should a red blood cell administration set be changed while a patient is being transfused? A commentary and review of the literature.

    Science.gov (United States)

    Blest, A; Roberts, M; Murdock, J; Watson, D; Brunskill, S

    2008-04-01

    Current recommendations vary with regard to the frequency of change of a red blood cell (RBC) administration set. A full review was undertaken to evaluate the recommendations for how often a RBC administration set should be changed while a patient is being transfused. Comprehensive searches of Medline, Embase, Cinahl, the Cochrane Library, handsearching of transfusion journals, guidelines and websites and contact with administration set manufacturers identified 32 relevant papers: 11 clinical updates; 11 guidelines; 5 manufacturer data sheets; 3 standards; 1 Department of Health report and 1 expert opinion. Recommendations varied widely across papers. There was no pattern in recommendation by paper type, date or country of origin. Recommendations were based on change of RBC administration set either after a given number of hours or number of RBC units. The recommendations varied widely and ranged from 4 to 48 h and from 'every unit' to 'several units'. The most frequent recommendations were change of RBC administration set after 12 h or 4 units. Methodological quality of the included papers is poor. There is no formal evidence base on which to support current recommendations or challenge the current British Committee for Standards in Haematology guideline. Targeted research aimed at establishing an evidence base may be warranted and would need to document other variables that can impact frequency of change, including type of filter, age of blood and duration of RBC transfusion. PMID:18399846

  18. Adverse blood transfusion outcomes: establishing causation.

    Science.gov (United States)

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  19. Anemia and Blood Transfusions in Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    M. Kamran Athar

    2012-01-01

    Full Text Available Anemia is common in critically ill patients. As a consequence packed red blood cell (PRBC transfusions are frequent in the critically ill. Over the past two decades a growing body of literature has emerged, linking PRBC transfusion to infections, immunosuppression, organ dysfunction, and a higher mortality rate. However, despite growing evidence that risk of PRBC transfusion outweighs its benefit, significant numbers of critically ill patients still receive PRBC transfusion during their intensive care unit (ICU stay. In this paper, we summarize the current literature concerning the impact of anemia on outcomes in critically ill patients and the potential complications of PRBC transfusions.

  20. Transfusion protocol in trauma

    Directory of Open Access Journals (Sweden)

    Kaur Paramjit

    2011-01-01

    Full Text Available Blood and blood components are considered drugs because they are used in the treatment of diseases. As with any drug, adverse effects may occur, necessitating careful consideration of therapy. Like any other therapeutic decision, the need for transfusion should be considered on the basis of risks and benefits and alternative treatments available to avoid over- and under-transfusion. This review is focused on the blood transfusion protocol in trauma patients with hemorrhagic shock. Besides, issues related to emergency and massive transfusion have also been elaborated. We conducted a comprehensive MEDLINE search and reviewed the relevant literature, with particular reference to emergency medical care in trauma.

  1. GRID INDEPENDENT FUEL CELL OPERATED SMART HOME

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Mohammad S. Alam

    2003-12-07

    A fuel cell power plant, which utilizes a smart energy management and control (SEMaC) system, supplying the power need of laboratory based ''home'' has been purchased and installed. The ''home'' consists of two rooms, each approximately 250 sq. ft. Every appliance and power outlet is under the control of a host computer, running the SEMaC software package. It is possible to override the computer, in the event that an appliance or power outage is required. Detailed analysis and simulation of the fuel cell operated smart home has been performed. Two journal papers has been accepted for publication and another journal paper is under review. Three theses have been completed and three additional theses are in progress.

  2. Stem cell therapy independent of stemness

    OpenAIRE

    Lee, Techung

    2012-01-01

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived h...

  3. Stem cell therapy independent of stemness.

    Science.gov (United States)

    Lee, Techung

    2012-12-26

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived hepatocyte growth factor (HGF) in two animal models of multiple sclerosis (MS), which is a progressive autoimmune disorder caused by damage to the myelin sheath and loss of oligodendrocytes. Although current MS therapies are directed toward attenuation of the immune response, robust repair of myelin sheath likely requires a regenerative approach focusing on long-term replacement of the lost oligodendrocytes. This approach appears feasible because adult organs contain various populations of multipotent resident stem/progenitor cells that may be activated by MSC trophic factors as demonstrated by Bai et al This commentary highlights and discusses the major findings of their studies, emphasizing the anti-inflammatory function and trophic cross-talk mechanisms mediated by HGF and other MSC-derived trophic factors in sustaining the treatment benefits. Identification of multiple functionally synergistic trophic factors, such as HGF and vascular endothelial growth factor, can eventually lead to the development of efficacious cell-free therapeutic regimens targeting a broad spectrum of degenerative conditions. PMID:23516128

  4. Addition of Sodium Pyruvate to Stored Red Blood Cells Attenuates Liver Injury in a Murine Transfusion Model

    Science.gov (United States)

    2016-01-01

    RBCs undergo numerous changes during storage and stored RBCs may induce adverse effects, ultimately resulting in organ injury in transfusion recipients. We tested the hypothesis that the addition of SP to stored RBCs would improve the quality of the stored RBCs and mitigate liver injury after transfusion in a murine model. RBCs were harvested from C57BL/6J mice and stored for 14 days in CPDA-1 containing either a solution of SP in saline or saline alone. Haemolysis, the 24-hour posttransfusion recovery, the oxygen-carrying capacity, and the SOD activity of stored RBCs were evaluated. The plasma biochemistry, hepatic MDA level, MPO activity, IL-6, TNF-α concentrations, and histopathology were measured two hours after the transfusion of stored RBCs. Compared with RBCs stored in CPDA-1 and saline, the addition of SP to stored RBCs restored their oxygen-carrying capacity and SOD activity, reduced the AST activity, BUN concentrations, and LDH activity in the plasma, and decreased the MDA level, MPO activity, and concentrations of IL-6 and TNF-α in the liver. These data indicate that the addition of SP to RBCs during storage has a beneficial effect on storage lesions in vitro and subsequently alleviates liver injury after the transfusion of stored RBCs in vivo.

  5. Quality of transfusion products in blood banking.

    Science.gov (United States)

    Franchini, Massimo; Capuzzo, Enrico; Turdo, Rosalia; Glingani, Claudia

    2014-03-01

    The primary goal in transfusion medicine and cellular therapies is to promote high standards of quality and produce ever safer and more efficacious products. The establishment of a transfusion service quality management system, which includes several organizational structures, responsibilities, policies, processes, procedures, and resources, is now mandatory and widely regulated worldwide. In this review, we summarize the current knowledge on the quality system in transfusion medicine as applied to the production of blood components, including red blood cells, platelets, and fresh frozen plasma. PMID:24474089

  6. Alternate Fuel Cell Membranes for Energy Independence

    Energy Technology Data Exchange (ETDEWEB)

    Storey, Robson, F.; Mauritz, Kenneth, A.; Patton, Derek, L.; Savin, Daniel, A.

    2012-12-18

    The overall objective of this project was the development and evaluation of novel hydrocarbon fuel cell (FC) membranes that possess high temperature performance and long term chemical/mechanical durability in proton exchange membrane (PEM) fuel cells (FC). The major research theme was synthesis of aromatic hydrocarbon polymers of the poly(arylene ether sulfone) (PAES) type containing sulfonic acid groups tethered to the backbone via perfluorinated alkylene linkages and in some cases also directly attached to the phenylene groups along the backbone. Other research themes were the use of nitrogen-based heterocyclics instead of acid groups for proton conduction, which provides high temperature, low relative humidity membranes with high mechanical/thermal/chemical stability and pendant moieties that exhibit high proton conductivities in the absence of water, and synthesis of block copolymers consisting of a proton conducting block coupled to poly(perfluorinated propylene oxide) (PFPO) blocks. Accomplishments of the project were as follows: 1) establishment of a vertically integrated program of synthesis, characterization, and evaluation of FC membranes, 2) establishment of benchmark membrane performance data based on Nafion for comparison to experimental membrane performance, 3) development of a new perfluoroalkyl sulfonate monomer, N,N-diisopropylethylammonium 2,2-bis(p-hydroxyphenyl) pentafluoropropanesulfonate (HPPS), 4) synthesis of random and block copolymer membranes from HPPS, 5) synthesis of block copolymer membranes containing high-acid-concentration hydrophilic blocks consisting of HPPS and 3,3'-disulfonate-4,4'-dichlorodiphenylsulfone (sDCDPS), 6) development of synthetic routes to aromatic polymer backbones containing pendent 1H-1,2,3-triazole moieties, 7) development of coupling strategies to create phase-separated block copolymers between hydrophilic sulfonated prepolymers and commodity polymers such as PFPO, 8) establishment of basic

  7. [Correct preparation of a transfusion: Part 1].

    Science.gov (United States)

    Strobel, E; Henschler, R

    2014-09-01

    The administration of blood products is strictly regulated. Several weeks before the operation the preparation for transfusion begins with optimizing the patient's hematological and hemostaseological situation. In elective surgery blood group testing and antibody screening are performed soon after admission of the patient. The identification of the blood sample is important. Informed consent of the recipient has to be obtained. On the day before the operation a further blood sample is necessary for cross-matching if red blood cells are to be transfused. Usually blood products are issued for immediate administration. Before transfusion begins the blood product has to be checked, the identity of the patient must be controlled and in the case of red blood cell transfusions the AB0 bedside test has to be performed. PMID:25085082

  8. Transfusion practice in hip arthroplasty - a nationwide study

    DEFF Research Database (Denmark)

    Jans, Øivind; Kehlet, H; Hussain, Zubair Butt;

    2011-01-01

    Background and Objectives The optimal transfusion strategy in hip arthroplasty remains controversial despite existing guidelines. The aim of this study was to evaluate the transfusion practice in patients undergoing primary total hip arthroplasty (THA) or revision total hip arthroplasty (RTHA......) in Denmark. Materials and Methods We performed a retrospective cohort study of all patients undergoing THA or RTHA in Denmark in 2008. Primary outcomes were intercentre variation in red blood cell (RBC) transfusion rates and the timing of transfusion related to surgery. Results Six thousand nine hundred...... thirty-two THA patients and 1132 RTHA patients were included for analysis of which 1674 (24%) THA and 689 (61%) RTHA patients received RBC transfusion. Of these, 47% of THA and 73% of RTHA patients received transfusion on the day of surgery. Transfusion rates between centres varied from 7 to 71...

  9. Helper cell-independent cytotoxic clones in man

    OpenAIRE

    1982-01-01

    We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.

  10. Alloimmunization among transfusion-dependent thalassemia patients

    OpenAIRE

    Sadeghian Mohammad; Keramati Mohammad; Badiei Zahra; Ravarian Mehrangiz; Ayatollahi Hossein; Rafatpanah Houshang; Daluei Mohammad

    2009-01-01

    Background: Thalassemia is a common hemoglobin disorder in Iran and one of the major public health problems. Although blood transfusions are lifesavers for thalassemia patients, they may be associated with some complications especially erythrocyte alloimmunization. The purpose of this study was to investigate the prevalence of red blood cell alloantibodies and to determine types of these antibodies among multiple-transfused thalassemic patients. Materials and Methods: A total of 313 thalas...

  11. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  12. [Autologous blood transfusion].

    Science.gov (United States)

    Rosencher, N; Conseiller, C

    2001-06-30

    Autologous blood transfusion techniques are the principal means of reducing allogeneic blood exposure. Those techniques were developed in order to prevent the risk of contamination by viruses, mainly HVB, HCV and HIV. However that risk has become so small that all studies show an exorbitant cost/efficiency ratio. Autologous blood transfusion would therefore be of no interest in terms of public health but a recent experimental study suggested a possible transmission of the BSE agent through blood. Until the matter is settled, the precaution principle means we should prefer alternative techniques to allogeneic blood whenever possible, hence a renewed interest in autologous transfusion. PMID:11503506

  13. [Single-donor protocol: Transfusion practices and multiple transfusion risk factors in neonatal intensive care unit].

    Science.gov (United States)

    Dollat, C; Pierron, C; Keslick, A; Billoir, E; François, A; Jarreau, P-H

    2016-09-01

    In France since 2002, the single-donor transfusion protocol, using four pediatric units from the same adult donor's packed red blood cells (PRBCs) in multiply transfused newborns, is recommended in preterm neonates to reduce the risks of infection and alloimmunization. This protocol is controversial, however, because it causes the transfusion of stored blood, which could have adverse consequences. Before the new recommendations of the French Haute Autorité de santé (National authority for health) in 2015, we conducted a national practice survey in 63 neonatal intensive care units (NICU) and a retrospective study of the characteristics of 103 children transfused within our unit, to better target beneficiaries. The practice survey showed that 30 % of French NICUs no longer used the protocol in 2014, due to logistical or financial problems, or concerns about the transfusion of stored blood. The practices were heterogeneous. Few NICUs used a written protocol. In our NICU, the use of single-donor protocol involved the use of units stored for more than 20 days in half of the cases beginning with the third unit used. Six-term newborns were mainly transfused once, which does not seem to warrant the single-donor transfusion protocol. The use of this protocol caused the loss of 50 % of the manufactured units, which go unused. In multivariate analysis, two factors were predictive of multiple transfusion within our population of 95 premature neonates undergoing transfusion: low-term and a high Clinical Risk Index for Babies (CRIB) score. The risk of multiple transfusions would be reduced by about 15 % for each additional week of gestation and approximately 16 % per point within the CRIB score. These variables integrated into a statistical model predict the risk of multiplying transfusions. According to the ROC curve, a calculated risk higher than 50 % is the appropriate cut-off value to transfuse with the single-donor transfusion protocol. This would limit its

  14. Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    YOU Yong; LI Qiu-bai; CHEN Zhi-chao; LI Wei-ming; XIA Ling-hui; ZHOU Hao; ZOU Ping

    2008-01-01

    Background Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (alIo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after alIo-HSCT.Methods Seven patients, median age 34 years, with relapse of acute leukaemia after alIo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range,38-185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.Results Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value ≥0.5x109/L and for platelet value >20x109/L were 13 days (range, 10-18 days) and 15 days (range, 11-24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.Conclusions Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after alIo-HSCT. The disease free state of patients may increase, thou.gh with

  15. Comparison of Efficacy of Prestorage with Poststorage Leukocytoreduction Filters in Transfusion Dependent Thalassemic Patients

    Directory of Open Access Journals (Sweden)

    H. Isfahani

    2010-07-01

    Full Text Available Introduction & Objective: Cellular blood products such as whole blood, packed RBC and platelet concentrate may contain a large number of donor leukocytes. These transfused cells are responsible for several transfusion reactions which include febrile reactions, platelet refractoriness due to alloimmunization and some cell associated virus transmission, especially cytomegalovirus. Advances in biotechnology resulted in production of filters capable of depleting residual leukocytes below the threshold receded to prevent these complications. The aim of this study was to determine the efficacy of prestorage and poststorage leukocyte reduction filters.Materials & Methods: In this experimental study 140 leukocyte filters used in patients with major thalassemia with age range of 1 to 18 years old were studied. They received packed RBC with pre storage or post storage filtration in pediatric hematology clinic of Be’sat hospital, Hamadan,Iran. In addition to filter efficiency, some transfusion reactions such as hypotension, urticaria, flushing, fever and chills were analyzed with chi-square and independent t-test.Results: Calculated efficiencies of pre storage and post storage filtration were 99.70%±69% and 92.74%±12.47% respectively, which is statistically significant (P=0.000. Fever, chills, urticaria and flushing which are some transfusion reactions, were not seen in any patients received filtrated packed RBC. No transfusion complication except hypotension (which was seen in 14 patients in both groups was seen. Maximum remained leukocyte in pre storage packed RBC was 20/mm3 and 524/mm3 in post storage blood.Conclusion: According to the calculated standard deviation, pre storage leukocyte filters are superior to post storage filters, and so post storage filtration is not a reliable method to reduce remaining white blood cells in transfused blood.

  16. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

  17. Smooth muscle cells largely develop independently of functional hemogenic endothelium

    Directory of Open Access Journals (Sweden)

    Monika Stefanska

    2014-01-01

    Full Text Available Vascular smooth muscle cells represent a major component of the cardiovascular system. In vitro studies have shown that FLK1+ cells derived from embryonic stem (ES cells can differentiate into both endothelial and smooth muscle cells. These FLK1+ cells also contain a mesodermal precursor, the hemangioblast, able to produce endothelial, blood and smooth muscle cells. The generation of blood precursors from the hemangioblast was recently shown to occur through a transient cell population of specialised endothelium, a hemogenic endothelium. To date, the lineage relationship between this cell population and smooth muscle cell progenitors has not been investigated. In this study, we generated a reporter ES cell line in which expression of the fluorescent protein H2B-VENUS is driven by the α-smooth muscle actin (α-SMA regulatory sequences. We demonstrated that this reporter cell line efficiently trace smooth muscle development during ES cell differentiation. Although some smooth muscle cells are associated with broad endothelial development, we established that smooth muscle cells are mostly generated independently from a specialised functional hemogenic endothelium. This study provides new and important insights into hematopoietic and vascular development, which may help in driving further progress towards the development of bioengineered vascular grafts for regenerative medicine.

  18. [A RhD negative patient failed to produce detectable anti-D after transfusion of 35 units of RhD positive red blood cells].

    Science.gov (United States)

    Lee, Won Mok; Kim, Ji Hae; Ha, Jung Sook; Ryoo, Nam Hee; Jeon, Dong Seok; Kim, Jae Ryong; Cho, Duck

    2007-10-01

    In the present day, pretransfusion tests include ABO and RhD grouping, antibody screening, antibody identification, and cross matching. Although error rates for these tests have decreased compared to those in the past, clerical errors still occur. When exposed to RhD positive RBCs, a RhD negative person can produce anti-D that causes a severe hemolytic disease of the fetus and the newborn in addition to hemolytic transfusion reactions. Therefore, administration of RhD positive RBCs to a RhD negative person should be avoided. We experienced a RhD negative patient who had been misidentified as positive and transfused 35 units of RhD positive RBCs eight years ago, but did not have detectable anti-D in present. The red cells of the patient showed no agglutination with the anti-D reagent and a negative result in the standard weak D test. The multiplex PCR with sequence-specific priming revealed that the patient was RhD negative. PMID:18094603

  19. Factors associated with persistence of red blood cell antibodies in woman after pregnancies complicated by fetal alloimmune haemolytic disease treated with intrauterine transfusions.

    Science.gov (United States)

    Verduin, Esther P; Brand, Anneke; van de Watering, Leo M G; Claas, Frans H J; Oepkes, Dick; Lopriore, Enrico; Doxiadis, Ilias I N; Schonewille, Henk

    2015-02-01

    Red blood cell (RBC) antibodies can persist for decades or decrease quickly to undetectable levels. Antibody persistence has not been systematically studied. Women whose children are treated with intrauterine transfusions (IUT) for haemolytic disease of the fetus (HDFN) often produce additional antibodies, which can be evoked by the intrauterine transfusion or by fetomaternal haemorrhage during the procedure. Factors associated with persistence of both the antibodies responsible for HDFN and additional antibodies were studied in 260 women whose children were treated with IUT between 1988 and 2008. They possessed 499 (205 anti-D and 294 non-D) antibodies after the last IUT. After a median follow-up of 8·7 years, all 260 antibodies primarily responsible for HDFN had persisted. Additional antibodies directed against antigens of the children persisted in 70·6%, and in 32·3% if they were not child-specific (P < 0·001). Antibodies induced by irradiated IUT persisted in only 7·1%. Multivariate analyses showed that non-HDFN antibody persistence was dependent on the antibody titre and specificity. In conclusion, persistence of antibodies mainly depends on antibody strength and specificity. Difference between fetal or non-fetal immunogens suggests maintenance of antigenic stimulation possibly by long-term fetomaternal chimerism. PMID:25244566

  20. The price of independence: cell separation in fission yeast.

    Science.gov (United States)

    Martín-García, Rebeca; Santos, Beatriz

    2016-04-01

    The ultimate goal of cell division is to give rise to two viable independent daughter cells. A tight spatial and temporal regulation between chromosome segregation and cytokinesis ensures the viability of the daughter cells. Schizosaccharomyces pombe, commonly known as fission yeast, has become a leading model organism for studying essential and conserved mechanisms of the eukaryotic cell division process. Like many other eukaryotic cells it divides by binary fission and the cleavage furrow undergoes ingression due to the contraction of an actomyosin ring. In contrast to mammalian cells, yeasts as cell-walled organisms, also need to form a division septum made of cell wall material to complete the process of cytokinesis. The division septum is deposited behind the constricting ring and it will constitute the new ends of the daughter cells. Cell separation also involves cell wall degradation and this process should be precisely regulated to avoid cell lysis. In this review, we will give a brief overview of the whole cytokinesis process in fission yeast, from the positioning and assembly of the contractile ring to the final step of cell separation, and the problems generated when these processes are not precise. PMID:26931605

  1. Serial haematology results in transfused and non-transfused dogs naturally infected with Babesia rossi

    Directory of Open Access Journals (Sweden)

    E. Scheepers

    2011-04-01

    Full Text Available This prospective longitudinal study investigated the progression of haematological changes in 32 transfused and 54 non-transfused dogs naturally infected with Babesia rossi over the 1st 6 days following diagnosis and treatment. The effect of patient age on the results of complete blood counts was determined. Haematology data were analysed at presentation and at 24 hours, 3 days and 6 days after presentation. Dogs were treated with diminazene aceturate at diagnosis and a blood transfusion was given if deemed clinically required. Mildly to moderately regenerative normocytic normochromic anaemia was observed in all dogs throughout the study period. Transfused dogs more often had an inflammatory leukogram at presentation and at 24 hours, than dogs that were not transfused. In dogs with a left shift, a concurrent normal or decreased segmented neutrophil count was found more commonly than neutrophilia. Severe thrombocytopenia that resolved within a week was common. Blood transfusion alleviated the anaemia, but had no significant effect on white blood cell or platelet responses. Blood cell responses were not significantly influenced by age. In conclusion, the red blood cell and white blood cell responses were less than expected in dogs with babesiosis, given the degree of anaemia and inflammation present. The magnitude of thrombocytopenia and rapid return of the platelet count to normal suggested a possible immune-mediated mechanism for the thrombocytopenia.

  2. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F;

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...... ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.......0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment....

  3. Age of transfused blood is not associated with increased postoperative adverse outcome after cardiac surgery.

    LENUS (Irish Health Repository)

    McKenny, M

    2011-05-01

    This study investigated the hypothesis that storage age of transfused red blood cells (RBCs) is associated with adverse outcome after cardiac surgery, and examined association between volume of RBC transfusions and outcome after cardiac surgery.

  4. Transfusion-related mortality after primary hip arthroplasty - an analysis of mechanisms and confounders

    DEFF Research Database (Denmark)

    Jans, O; Kehlet, H; Johansson, P I

    2012-01-01

    Background and Objectives Bleeding and postoperative anaemia after total hip arthroplasty (THA) may trigger transfusion of red blood cells (RBC). However, large observational studies have reported associations between RBC transfusion and increased postoperative morbidity and mortality. As major b...

  5. Survival of red blood cells after transfusion: a comparison between red cells concentrates of different storage periods.

    NARCIS (Netherlands)

    Luten, M.; Roerdinkholder-Stoelwinder, B.; Schaap, N.P.M.; Grip, W.J. de; Bos, H.J.; Bosman, G.J.C.G.M.

    2008-01-01

    BACKGROUND: The use of fresh red blood cells (RBCs) is recommended for critically ill patients and patients undergoing surgery, although there is no conclusive evidence that this is beneficial. In this follow-up study, the short-term and the long-term recovery of irradiated, leukoreduced RBCs transf

  6. Perioperative transfusion threshold and ambulation after hip revision surgery

    DEFF Research Database (Denmark)

    Nielsen, Kamilla; Johansson, Pär I; Dahl, Benny;

    2014-01-01

    BACKGROUND: Transfusion with red blood cells (RBC) may be needed during hip revision surgery but the appropriate haemoglobin concentration (Hb) threshold for transfusion has not been well established. We hypothesized that a higher transfusion threshold would improve ambulation after hip revision...... received RBC. CONCLUSIONS: A Hb transfusion threshold of 8.9 g/dL was associated with a statistically significantly faster TUG after hip revision surgery compared to a threshold of 7.3 g/dL but the clinical importance is questionable and the groups did not differ in Hb at the time of testing....

  7. HIF-1α Promotes A Hypoxia-Independent Cell Migration.

    Science.gov (United States)

    Li, Liyuan; Madu, Chikezie O; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.

  8. Laryngospasm after autologous blood transfusion.

    Science.gov (United States)

    Hong, Jung; Grecu, Loreta

    2006-07-01

    Although perioperative autologous blood transfusions are associated with few side effects, transfusion reactions can occur and can be life-threatening. We report the occurrence of postoperative laryngospasm in a patient who underwent spinal anesthesia for hip surgery. The laryngospasm could not be attributed to any cause other than the autologous blood transfusion and recurred when the transfusion was restarted. Laryngospasm was successfully treated both times with positive pressure ventilation. Autologous transfusions can trigger febrile nonhemolytic transfusion reactions, which may result in airway compromise.

  9. Na+-independent phosphate transport in Caco2BBE cells

    Science.gov (United States)

    Candeal, Eduardo; Caldas, Yupanqui A.; Guillén, Natalia; Levi, Moshe

    2014-01-01

    Pi transport in epithelia has both Na+-dependent and Na+-independent components, but so far only Na+-dependent transporters have been characterized in detail and molecularly identified. Consequently, in the present study, we initiated the characterization and analysis of intestinal Na+-independent Pi transport using an in vitro model, Caco2BBE cells. Only Na+-independent Pi uptake was observed in these cells, and Pi uptake was dramatically increased when cells were incubated in high-Pi DMEM (4 mM) from 1 day to several days. No response to low-Pi medium was observed. The increased Pi transport was mainly caused by Vmax changes, and it was prevented by actinomycin D and cycloheximide. Pi transport in cells grown in 1 mM Pi (basal DMEM) decreased at pH > 7.5, and it was inhibited with proton ionophores. Pi transport in cells incubated with 4 mM Pi increased with alkaline pH, suggesting a preference for divalent phosphate. Pi uptake in cells in 1 mM Pi was completely inhibited only by Pi and partially inhibited by phosphonoformate, oxalate, DIDS, SITS, SO42−, HCO3−, and arsenate. This inhibition pattern suggests that more than one Pi transporter is active in cells maintained with 1 mM Pi. Phosphate transport from cells maintained at 4 mM Pi was only partially inhibited by phosphonoformate, oxalate, and arsenate. Attempts to identify the responsible transporters showed that multifunctional anion exchangers of the Slc26 family as well as members of Slc17, Slc20, and Slc37 and the Pi exporter xenotropic and polytropic retrovirus receptor 1 are not involved. PMID:25298422

  10. Red Blood Cell Transfusions and Iron Therapy for Patients Presenting with Acute Upper Gastrointestinal Bleeding: A Survey of Canadian Gastroenterologists and Hepatologists

    Science.gov (United States)

    Fortinsky, Kyle J.; Razik, Roshan; Spiegle, Gillian; Gallinger, Zane R.; Grover, Samir C.; Pavenski, Katerina; Weizman, Adam V.; Kwapisz, Lukasz; Mehta, Sangeeta; Gray, Sarah

    2016-01-01

    Introduction. There is limited data evaluating physician transfusion practices in patients with acute upper gastrointestinal bleeding (UGIB). Methods. A web-based survey was sent to 500 gastroenterologists and hepatologists across Canada. The survey included clinical vignettes where physicians were asked to choose transfusion thresholds. Results. The response rate was 41% (N = 203). The reported hemoglobin (Hgb) transfusion trigger differed by up to 50 g/L. Transfusions were more liberal in hemodynamically unstable patients compared to stable patients (mean Hgb of 86.7 g/L versus 71.0 g/L; p iron to patients with UGIB who are anemic upon discharge. Conclusions. The transfusion practices of gastroenterologists in the management of UGIB vary widely and more high-quality evidence is needed to help assess the efficacy and safety of selected transfusion thresholds in varying patients presenting with UGIB. PMID:27446847

  11. Detrimental effects of perioperative blood transfusion

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1995-01-01

    Evidence suggests that perioperative allogeneic blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative operation. This has been attributed to immunosuppression. Several authors have suggested that filtered whole blood and/or red...... cell concentrate, or leucocyte- and buffy coat-reduced red cells in artificial medium or their own plasma, may reduce postoperative immunosuppression. It was also anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown...

  12. Monitoring compliance with transfusion guidelines in hospital departments by electronic data capture

    DEFF Research Database (Denmark)

    Norgaard, Astrid; De Lichtenberg, Trine Honnens; Nielsen, Jens;

    2014-01-01

    BACKGROUND: The practice of transfusing red blood cells is still liberal in some centres suggesting a lack of compliance with guidelines recommending transfusion of red blood cells at haemoglobin levels of 6-8 g/dL in the non-bleeding patient. Few databases provide ongoing feedback of data on pre-transfusion...... haemoglobin levels at the departmental level. In a tertiary care hospital, no such data were produced before this study. Our aim was to establish a Patient Blood Management database based on electronic data capture in order to monitor compliance with transfusion guidelines at departmental and hospital levels....... MATERIALS AND METHODS: Hospital data on admissions, diagnoses and surgical procedures were used to define the populations of patients. Data on haemoglobin measurements and red blood cell transfusions were used to calculate pre-transfusion haemoglobin, percentage of transfused patients and transfusion...

  13. B cells mediate chronic allograft rejection independently of antibody production.

    Science.gov (United States)

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.

  14. B cells mediate chronic allograft rejection independently of antibody production.

    Science.gov (United States)

    Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A; Ippolito, Renee; Zahalka, Salwa; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A; Ramaswami, Balathiripurasundari; Lund, Frances E; Chalasani, Geetha

    2014-03-01

    Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture. PMID:24509079

  15. Novel web-based real-time dashboard to optimize recycling and use of red cell units at a large multi-site transfusion service

    Directory of Open Access Journals (Sweden)

    Christopher Sharpe

    2014-01-01

    Full Text Available Background: Effective blood inventory management reduces outdates of blood products. Multiple strategies have been employed to reduce the rate of red blood cell (RBC unit outdate. We designed an automated real-time web-based dashboard interfaced with our laboratory information system to effectively recycle red cell units. The objective of our approach is to decrease RBC outdate rates within our transfusion service. Methods: The dashboard was deployed in August 2011 and is accessed by a shortcut that was placed on the desktops of all blood transfusion services computers in the Capital District Health Authority region. It was designed to refresh automatically every 10 min. The dashboard provides all vital information on RBC units, and implemented a color coding scheme to indicate an RBC unit′s proximity to expiration. Results: The overall RBC unit outdate rate in the 7 months period following implementation of the dashboard (September 2011-March 2012 was 1.24% (123 units outdated/9763 units received, compared to similar periods in 2010-2011 and 2009-2010: 2.03% (188/9395 and 2.81% (261/9220, respectively. The odds ratio of a RBC unit outdate postdashboard (2011-2012 compared with 2010-2011 was 0.625 (95% confidence interval: 0.497-0.786; P < 0.0001. Conclusion: Our dashboard system is an inexpensive and novel blood inventory management system which was associated with a significant reduction in RBC unit outdate rates at our institution over a period of 7 months. This system, or components of it, could be a useful addition to existing RBC management systems at other institutions.

  16. Problems of multiple transfusions.

    Science.gov (United States)

    GARDNER, F H

    1958-02-01

    The use of blood infusion in large amounts is increasing sharply. Increased knowledge of blood group antigens has alerted physicians to the possible hazards of hemolytic reactions to subgroups that must be eliminated by proper cross-matching techniques. Multiple transfusions of preserved blood often defeat their purpose in control of bleeding, for thrombocytopenia is enhanced. Careful selection of blood or preparations of plasma concentrates offer increased protection to the recipient.Plastic bag equipment increases the yield of viable platelets and keeps blood in usable condition for longer periods of storage. The use of multiple transfusions has complicated the selection of preserved blood to control pigment metabolism. PMID:13500210

  17. Platelet transfusion - the new immunology of an old therapy.

    Science.gov (United States)

    Stolla, Moritz; Refaai, Majed A; Heal, Joanna M; Spinelli, Sherry L; Garraud, Olivier; Phipps, Richard P; Blumberg, Neil

    2015-01-01

    Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged serious risks of platelet transfusion include viral transmission, bacterial sepsis, and acute lung injury. Less serious adverse effects include allergic and non-hemolytic febrile reactions. Rare hemolytic reactions have occurred due to a common policy of transfusing without regard to ABO type. In the last decade or so, new concerns have arisen; platelet-derived lipids are implicated in transfusion-related acute lung injury after transfusion. With the recognition that platelets are immune cells came the discoveries that supernatant IL-6, IL-27 sCD40L, and OX40L are closely linked to febrile reactions and sCD40L with acute lung injury. Platelet transfusions are pro-inflammatory, and may be pro-thrombotic. Anti-A and anti-B can bind to incompatible recipient or donor platelets and soluble antigens, impair hemostasis and thus increase bleeding. Finally, stored platelet supernatants contain biological mediators such as VEGF and TGF-β1 that may compromise the host versus tumor response. This is particularly of concern in patients receiving many platelet transfusions, as for acute leukemia. New evidence suggests that removing stored supernatant will improve clinical outcomes. This new view of platelets as pro-inflammatory and immunomodulatory agents suggests that innovative approaches to improving platelet storage and pre-transfusion manipulations to reduce toxicity could substantially improve the efficacy and safety of this long-employed therapy. PMID:25699046

  18. Transfusion-Transmitted Babesia microti.

    Science.gov (United States)

    Fang, Deanna C; McCullough, Jeffrey

    2016-07-01

    Because testing of donors for Babesia microti has become available, it is important to determine the kinds of patients who should receive B microti-tested blood. We searched PubMed, AABB abstracts, and FDA Web site to identify all cases of transfusion-transmitted babesiosis (TTB). Cases were analyzed for underlying medical condition, age, presence of spleen, and reason for transfusion in relation to 5 classes of recipient outcome severity. Sixty-seven reports included 256 transfusion cases where donor tested positive for B microti, 165 of which resulted in TTB. Sixty recipients did not develop disease or become test positive, and test results were not known for 31 more. The 165 cases of TTB involved hematologic (19%), neonate (10%), cardiovascular (8%), and gastrointestinal (6%) patients. Thirty-two (19%) of the 165 infected patients died with death attributed to babesiosis in 25 of the cases. Nine (5%) were asymptomatic, 27 (16%) were symptomatic but had uncomplicated disease, and 16 (10%) had complicated disease. The severity of disease was mixed among many disease categories. Patients >65 years of age included the largest number of recipients (59/165, 36%) and deaths (11/32, 34%), although deaths occurred in other age groups as well. TTB cases were predominantly due to red cells (133 of 140 specified units), with red blood cell units processed in a variety of ways and at all storage duration. TTB with complicated babesiosis and/or death occurred in patients of all age groups and with a variety of underlying medical conditions. PMID:27260107

  19. Logistics of massive transfusions.

    Science.gov (United States)

    DeLoughery, Thomas G

    2010-01-01

    Care of the patient with massive bleeding involves more than aggressive surgery and infusion of large amounts of blood products. The proper management of massive transfusions-whether they are in trauma patients or other bleeding patients-requires coordination of the personnel in the surgical suite or the emergency department, the blood bank, and laboratory.

  20. Blood transfusion and dermatology:

    OpenAIRE

    Al Aboud, Ahmad; Al Aboud, Khalid; Al Hawsawi, Khalid; Jain, Nipun; Ramesh, V.

    2006-01-01

    Blood transfusion is an accepted therapeutic procedure in all specialties of medicine. In dermatology, specialized techniques like plasmapheresis and extracorporeal photochemotherapy have provided a good treatment option in immune-mediated disorders like bullous dermatoses, collagen vascular diseases and cutaneous lymphomas. Other anecdotal and less substantiated reports point to its use in chronic disorders like atopic dermatitis and psoriasis. Untowarddermatological manifestations include m...

  1. Economics of transfusion

    NARCIS (Netherlands)

    Yeh, JM; Botteman, M; Pashos, CL; Postma, MJ; Staginnus, U

    2002-01-01

    Despite recent advances in blood screening techniques, transfusions are not risk-free procedures. Screening for viral and bacterial infections as well as other newly emerging agents continues to attract attention in the medical and health policy communities. At the same time, as healthcare costs ris

  2. Epidemiology of Massive Transfusion

    DEFF Research Database (Denmark)

    Halmin, Märit; Chiesa, Flaminia; Vasan, Senthil K;

    2016-01-01

    in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day...

  3. Transfusion reaction in a case with the rare Bombay blood group

    OpenAIRE

    Hayedeh Javadzadeh Shahshahani; Mohamad Reza Vahidfar; Seyed Ali Khodaie

    2013-01-01

    Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights ...

  4. Retinopathy of Prematurity and Blood Transfusion Protocols

    Directory of Open Access Journals (Sweden)

    P Mohagheghi

    2003-10-01

    Full Text Available To determine the role of blood transfusion protocols on retinopathy of prematurity (ROP, a prospective cohort study on 57 premature infants under 1501 grams birth weight was performed. Fourteen day-old infants were divided into two groups randomly. Infants in group 1 (n=27 received packed red blood cell transfusion only if specific medical signs were met and their hematocrit level was under 30%. Infants in group 2 (n=30 received blood transfusion to maintain their hematocrit level > 40% regardless of their signs. All infants had an eye examination by indirect ophthalmoscopy from 28 to 40 days of life for detecting ROP. We did not find any significant difference in ROP incidence between both groups.

  5. Blood transfusion practices in cancer surgery

    Directory of Open Access Journals (Sweden)

    Juan P Cata

    2014-01-01

    Full Text Available Cancer patients are commonly transfused with blood products immediately before, during or after major surgery. Blood loss and haemodilution are the most common causes of red blood cells (RBCs administration and coagulopathies are the indications for the infusion of fresh-frozen plasma (FFP, cryoprecipitates and platelets. Transfusion-related immune modulation is a complication associated with the administration of blood products. A decreased immune surveillance as a consequence of blood transfusions has been linked to cancer recurrence and progression. Moreover, soluble factors present in packed RBCs, platelets and FFP can directly stimulate tumour growth and spread. Two meta-analyses suggest that the administration of blood products is associated with shorter recurrence-free survival and overall survival after colorectal cancer surgery. More studies are needed to show such association in different cancer patient populations.

  6. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Directory of Open Access Journals (Sweden)

    Yuwei Jiang

    2014-11-01

    Full Text Available Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.

  7. Recurrent abortions and lymphocyte transfusions.

    Science.gov (United States)

    Bjercke, S

    1994-05-01

    Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo. PMID:8009967

  8. Intraoperative transfusion threshold and tissue oxygenation

    DEFF Research Database (Denmark)

    Nielsen, K; Dahl, B; Johansson, P I;

    2012-01-01

    Transfusion with allogeneic red blood cells (RBCs) may be needed to maintain oxygen delivery during major surgery, but the appropriate haemoglobin (Hb) concentration threshold has not been well established. We hypothesised that a higher level of Hb would be associated with improved subcutaneous...

  9. Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project

    Directory of Open Access Journals (Sweden)

    Bernabeu-Wittel Máximo

    2012-02-01

    Full Text Available Abstract Background Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm versus i.v. ferric carboxymaltose (FE arm versus a placebo (PLACEBO arm in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Methods/Design Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU, or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. Discussion We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491.

  10. Interventions to reduce wrong blood in tube errors in transfusion: a systematic review.

    Science.gov (United States)

    Cottrell, Susan; Watson, Douglas; Eyre, Toby A; Brunskill, Susan J; Dorée, Carolyn; Murphy, Michael F

    2013-10-01

    This systematic review addresses the issue of wrong blood in tube (WBIT). The objective was to identify interventions that have been implemented and the effectiveness of these interventions to reduce WBIT incidence in red blood cell transfusion. Eligible articles were identified through a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, Cinahl, BNID, and the Transfusion Evidence Library to April 2013. Initial search criteria were wide including primary intervention or observational studies, case reports, expert opinion, and guidelines. There was no restriction by study type, language, or status. Publications before 1995, reviews or reports of a secondary nature, studies of sampling errors outwith transfusion, and articles involving animals were excluded. The primary outcome was a reduction in errors. Study characteristics, outcomes measured, and methodological quality were extracted by 2 authors independently. The principal method of analysis was descriptive. A total of 12,703 references were initially identified. Preliminary secondary screening by 2 reviewers reduced articles for detailed screening to 128 articles. Eleven articles were eventually identified as eligible, resulting in 9 independent studies being included in the review. The overall finding was that all the identified interventions reduced WBIT incidence. Five studies measured the effect of a single intervention, for example, changes to blood sample labeling, weekly feedback, handwritten transfusion requests, and an electronic transfusion system. Four studies reported multiple interventions including education, second check of ID at sampling, and confirmatory sampling. It was not clear which intervention was the most effective. Sustainability of the effectiveness of interventions was also unclear. Targeted interventions, either single or multiple, can lead to a reduction in WBIT; but the sustainability of effectiveness is uncertain. Data on the pre- and postimplementation of

  11. Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

    Science.gov (United States)

    Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

    2016-04-01

    Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field.

  12. Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine.

    Science.gov (United States)

    Wu, Yu-Wen; Goubran, Hadi; Seghatchian, Jerard; Burnouf, Thierry

    2016-04-01

    Therapeutic and diagnostic applications of nanomedicine are playing increasingly important roles in human health. Various types of synthetic nanoparticles, including liposomes, micelles, and other nanotherapeutic platforms and conjugates, are being engineered to encapsulate or carry drugs for treating diseases such as cancer, cardiovascular disorders, neurodegeneration, and inflammations. Nanocarriers are designed to increase the half-life of drugs, decrease their toxicity and, ideally, target pathological sites. Developing smart carriers with the capacity to deliver drugs specifically to the microenvironment of diseased cells with minimum systemic toxicity is the goal. Blood cells, and potentially also the liposome-like micro- and nano-vesicles they generate, may be regarded as ideally suited to perform such specific targeting with minimum immunogenic risks. Blood cell membranes are "decorated" with complex physiological receptors capable of targeting and communicating with other cells and tissues and delivering their content to the surrounding pathological microenvironment. Blood cells, such as erythrocytes, have been developed as permeable carriers to release drugs to diseased tissues or act as biofactory allowing enzymatic degradation of a pathological substrate. Interestingly, attempts are also being made to improve the targeting capacity of synthetic nanoparticles by "decorating" their surface with blood cell membrane receptor-like biochemical structures. Research is needed to further explore the benefits that blood cell-derived microvesicles, as a Trojan horse delivery systems, can bring to the arsenal of therapeutic micro- and nanotechnologies. This short review focuses on the therapeutic roles that red blood cells and platelets can play as smart drug-delivery systems, and highlights the benefits that blood transfusion expertise can bring to this exciting and novel biomedical engineering field. PMID:27179926

  13. Reappraising the concept of massive transfusion in trauma

    DEFF Research Database (Denmark)

    Stanworth, Simon J; Morris, Timothy P; Gaarder, Christine;

    2010-01-01

    ABSTRACT : INTRODUCTION : The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens...... of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive...... transfusion requirements could allow early activation of blood bank protocols. METHODS : Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability...

  14. Thrombelastography Guides Transfusion Strategy

    OpenAIRE

    Bay Nielsen, Henning

    2009-01-01

    During surgery for an abdominal aortic aneurysm, coagulation may be impaired and the use of thrombelastography (TEG) is described in six patients with a perioperative blood loss of 3L. During surgery blood products were infused but not platelets. When the patients were admitted to the intensive care unit, the TEG report demonstrated a lowered MA value indicating impaired function of platelets. The use of TEG may guide transfusion strategy.

  15. Post-transfusion red cell alloimmunisation in patients with acute disorders and medical emergencies Aloimunização após transfusão de concentrado de hemácias em pacientes atendidos em um serviço de emergência

    Directory of Open Access Journals (Sweden)

    Francisco W. R. Santos

    2007-12-01

    Full Text Available Alloimmunisation following red cell transfusion is a complication in patients with chronic diseases requiring multiple transfusions. The aim of this study was to determine the frequency of alloimmunisation, to identify involved alloantibodies, to establish risk factors and to quantify the alloimmunisation risk in patients with acute disorders who received red cell transfusion at the Instituto Dr. José Frota from January 1999 to January 2001. Of the 5,690 recipients who received 16,547 units of red blood cells, 4,025 were men and 1,665 were women. Recipients with previous alloimmunisation or with time of hospital stay less than one week were excluded (n = 501. Red cell alloantibodies were detected in 120 recipients (2.1%: 60 men (1.49% and 60 women (3.60%. Alloimmunisation was 2.4 fold more frequent in women and 93.33% of the women were pregnant prevously. The average number of units transfused in the alloimmunised recipients was 4.68: 4.97 units in men and 4.40 units in women. In non-alloimmunised recipients the average was 2.87 units and the risk of alloimmunisation was 0.83%: 0.59% in men and 1.44% in women. The most frequent allo-antibodies were: anti-E (18.25% and anti-D (16.06% from a total of 137 allo-antibodies detected. The median time for detection of allo-antibodies was 20.88 days. The risk of alloimmunisation detected was high considering the average number of units transfused. The age of recipients and the longer life expectancy increase the probability of further transfusion requirements in this group. Our findings point out the necessity of modifications in the current medical transfusion support indication, including in patients with acute disorders in order to prevent alloimmunisation.A aloimunização eritrocitária após transfusão de concentrado de hemácias é uma complicação em pacientes com doenças crônicas que necessitam de transfusões de repetição. Esse estudo objetivou determinar a freqüência de aloimuniza

  16. [Effects of perioperative blood transfusion on the severity of postoperative infection].

    Science.gov (United States)

    Zhuang, Yuan; Zhang, Dong-Qing; Wang, Shu-Ying; Zhou, Wu; Pan, Ji-Chun; Wang, De-Qing

    2013-02-01

    This study was purposed to explore whether the blood transfusion of surgical patients can increase the severity of postoperative infection by a retrospective analysis of patients with postoperative infection in Chinese PLA General Hospital. By using a software "clinical transfusion database" developed by our department, 150 infected surgical cases were retrieved and divided into deep infection group and superficial infection group according to the infected location. These two groups were compared in term of the patient's age, duration of hospitalization, red blood cell transfusion volume, none-red cell transfusion volume, transfusion frequency and average transfusion volume. The results showed that red blood cell transfusion volume or none-red cells transfusion volume of patients with superficial infection was 4.50 (0 - 59) U or 2.95 (0 - 119.6) U, and that of deep infection was 9.00 (0 - 153) U and 8.05 (0 - 136.6) U, the differences was significant (P transfusion frequency showed the most significant difference, median in the patients with superficial infection was about 2 (1 - 31) times, less than the deep infection group about 4 (1 - 49) times (P transfusion volume. It is concluded that perioperative blood transfusion volume and frequency of surgical patients seems to display a positive correlation with the degree of postoperative infection.

  17. Impact of Transfusion on Cancer Growth and Outcome

    OpenAIRE

    Hadi A. Goubran; Mohamed Elemary; Miryana Radosevich; Jerard Seghatchian; Magdy El-Ekiaby; Thierry Burnouf

    2016-01-01

    For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of the...

  18. Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Larsen, A M; Leinøe, E B; Johansson, P I;

    2015-01-01

    OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before...

  19. Fulminant transfusion-associated graft-versus-host disease in a premature infant

    International Nuclear Information System (INIS)

    A fatal case of transfusion-associated graft-versus-host disease developed in a premature infant after receiving several blood products, including nonirradiated white blood cells. Transfusion-associated graft-versus-host disease can be prevented. Irradiation of blood products is the least controversial and most effective method. Treatment was unsuccessful in most reported cases of transfusion-associated graft-versus-host disease. Therefore irradiation of blood products before transfusing to patients susceptible to transfusion-associated graft-versus-host disease is strongly recommended

  20. [Successful treatment of an overwhelming infection with granulocyte transfusion in severe aplastic anemia patient undergoing allogeneic peripheral blood stem cell transplantation].

    Science.gov (United States)

    Kazuma, Yasuhiro; Ono, Yuichiro; Yonetani, Noboru; Imai, Yukihiro; Kawakami, Manabu; Hashimoto, Hisako; Ishikawa, Takayuki

    2016-04-01

    A 19-year-old woman complaining of fever and a sore throat was diagnosed with very severe aplastic anemia (AA) by bone marrow examination at a local hospital. Despite administration of antibiotics and granulocyte-colony stimulating factor to treat the soft tissue infection in her neck, her neutrophil count showed no increase. Because emergent allogeneic stem cell transplantation (SCT) was necessary, she was referred to our hospital. On admission, computed tomography revealed right-sided severe pharyngitis and lymphadenitis causing tracheal stenosis, and emergent intubation was required the next day. Granulocyte transfusion therapy (GTX) from related donors coupled with broad-spectrum antibiotic administration controlled the otherwise overwhelming infection. The patient received allogeneic peripheral blood SCT using a reduced-intensity conditioning regimen. After allogeneic SCT, successful engraftment was obtained. She was discharged from the hospital 59 days after allogeneic SCT. She remains alive and well, as of the latest follow up. This case clearly demonstrates that GTX is useful for controlling severe infection and enables patients with severe AA to receive allogeneic SCT safely. PMID:27169447

  1. The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

    Science.gov (United States)

    Wells, A W; Llewelyn, C A; Casbard, A; Johnson, A J; Amin, M; Ballard, S; Buck, J; Malfroy, M; Murphy, M F; Williamson, L M

    2009-12-01

    This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

  2. Pediatric Patient Blood Management Programs: Not Just Transfusing Little Adults.

    Science.gov (United States)

    Goel, Ruchika; Cushing, Melissa M; Tobian, Aaron A R

    2016-10-01

    Red blood cell transfusions are a common life-saving intervention for neonates and children with anemia, but transfusion decisions, indications, and doses in neonates and children are different from those of adults. Patient blood management (PBM) programs are designed to assist clinicians with appropriately transfusing patients. Although PBM programs are well recognized and appreciated in the adult setting, they are quite far from standard of care in the pediatric patient population. Adult PBM standards cannot be uniformly applied to children, and there currently is significant variation in transfusion practices. Because transfusing unnecessarily can expose children to increased risk without benefit, it is important to design PBM programs to standardize transfusion decisions. This article assesses the key elements necessary for a successful pediatric PBM program, systematically explores various possible pediatric specific blood conservation strategies and the current available literature supporting them, and outlines the gaps in the evidence suggesting need for further/improved research. Pediatric PBM programs are critically important initiatives that not only involve a cooperative effort between pediatric surgery, anesthesia, perfusion, critical care, and transfusion medicine services but also need operational support from administration, clinical leadership, finance, and the hospital information technology personnel. These programs also expand the scope for high-quality collaborative research. A key component of pediatric PBM programs is monitoring pediatric blood utilization and assessing adherence to transfusion guidelines. Data suggest that restrictive transfusion strategies should be used for neonates and children similar to adults, but further research is needed to assess the best oxygenation requirements, hemoglobin threshold, and transfusion strategy for patients with active bleeding, hemodynamic instability, unstable cardiac disease, and cyanotic cardiac

  3. Scientific and forensic standards for homologous blood transfusion anti-doping analyses.

    Science.gov (United States)

    Giraud, Sylvain; Robinson, Neil; Mangin, Patrice; Saugy, Martial

    2008-07-18

    Since the introduction in 2001 of a urine-based detection method for recombinant erythropoietin (rHuEPO), transfusion-doping practices have regained interest. To address this problem, an efficient antidoping test designed to obtain direct proof of allogeneic blood transfusion was developed and validated. This test, based on flow cytometry analysis of red blood cell (RBCs) phenotypes, was used to determine the absence or the presence of numerous RBCs populations in a blood sample. A such, it may constitute a direct proof of an abnormal blood population resulting from homologous transfusion. Single-blind and single-site studies were carried out to validate this method as a forensic quality standard analysis and to allow objective interpretation of real cases. The analysis of 140 blood samples containing different percentages (0-5%) of a minor RBCs population were carried on by four independent analysts. Robustness, sensitivity, specificity, precision and stability were assessed. ISO-accredited controls samples were used to demonstrate that the method was robust, stable and precise. No false positive results were observed, resulting in a 100% specificity of the method. Most samples containing a 1.5% minor RBCs population were unambiguously detected, yielding a 78.1% sensitivity. These samples mimicked blood collected from an athlete 3 months after a homologous blood transfusion event where 10% of the total RBCs present in the recipient originated in the donor. The observed false negative results could be explained by differences in antigen expression between the donor and the recipient. False negatives were more numerous with smaller minor RBCs populations. The method described here fulfils the ISO-17025 accreditation and validation requirements. The controls and the methodology are solid enough to determine with certainty whether a sample contains one or more RBCs populations. This variable is currently the best indicator for homologous blood transfusion doping.

  4. Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion. Nonlinear decay of adult red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Gemert, Martin J C van; Wijngaard, Jeroen P H M van den [Laser Centre and Department of Obstetrics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Pasman, Suzanne A; Vandenbussche, Frank P H A [Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Centre, Leiden (Netherlands); Lopriore, Enrico [Division of Neonatology, Department of Pediatrics, Leiden University Medical Centre, Leiden (Netherlands)], E-mail: m.j.vangemert@amc.uva.nl

    2008-07-07

    Recently, we derived equations relating the flow of adult red blood cells through a placental arterio-venous anastomosis with intra-uterine and post-natal measured adult hemoglobin concentrations. In this letter, we re-derived the equations, now including a more realistic nonlinear decay of adult red blood cells, and re-evaluated the measurement accuracy of the arterio-venous flow and the lifetime of the red blood cells. (letter to the editor)

  5. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  6. Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch.

    Science.gov (United States)

    Seidel, Hannah S; Kimble, Judith

    2015-11-09

    Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells--including germline stem cells--become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions--GLP-1/Notch signaling--becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

  7. Blood transfusion exposure in Denmark and Sweden

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Edgren, Gustaf; Rostgaard, Klaus;

    2009-01-01

    Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population.......Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population....

  8. Transfusion service disaster planning.

    Science.gov (United States)

    Bundy, K L; Foss, M L; Stubbs, J R

    2008-01-01

    The Mayo Clinic, in Rochester, Minnesota, recently set forth a directive to develop a Mayo Emergency Incident Command System (MEICS) plan to respond to major disasters. The MEICS plan that was developed interfaces with national response plans to ensure effective communication and coordination between our institution and local, state, and federal agencies to establish a common language and communication structure. The MEICS plan addresses multiple aspects of dealing with resource needs during a crisis, including the need for blood and transfusion medicine services. The MEICS plan was developed to supplement our current local emergency preparedness procedures and provide a mechanism for responding to the escalating severity of an emergency to deal with situations of a magnitude that is outside the normal experience. A plan was developed to interface the existing Transfusion Medicine disaster plan standard operating procedures (SOP) with the institutional and Department of Laboratory Medicine (DLMP) MEICS plans. The first step in developing this interface was defining MEICS. Other major steps were defining the chain of command, developing a method for visually indicating who is "in charge," planning communication, defining the actions to be taken, assessing resource needs, developing flowcharts and updating SOPs, and developing a blood rationing team to deal with anticipated blood shortages. Several key features of the interface and updated disaster plan that were developed are calling trees for response personnel, plans for relocating leadership to alternative command centers, and action sheets to assist with resource assessment. The action sheets also provide documentation of key actions by response personnel.

  9. TRANSFUSION REQUIREMENT AND COMPLICATION IN CHILDREN ADMITTED IN A TERTIARY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Booma

    2016-05-01

    Full Text Available BACKGROUND Indications for transfusion include symptomatic anaemia, haemolytic anaemia, haematological malignancy, acute sickle cell crisis, and acute blood loss of more than 30 percent of blood volume, sepsis, etc. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Platelet transfusion is indicated to prevent haemorrhage in patients with thrombocytopenia or platelet function defects. Cryoprecipitate is used in cases of hyperfibrinogenaemia, which most often occurs in the setting of massive haemorrhage or consumptive coagulopathy, factor VIII deficiency and Von Willebrand disease as an alternate to specific component therapy. Transfusion-related infections are less common than non-infectious complications. All non-infectious complications of transfusion are classified as non-infectious serious hazards of transfusion. Acute complications occur within minutes to 24 hours of the transfusion, whereas delayed complications may develop days, months or even years later. Blood transfusion can be a lifesaving procedure, but it has risks, including infectious and non-infectious complications. There is debate in the medical literature concerning the appropriate use of blood and blood products. Clinical trials investigating their use suggest that waiting to transfuse at lower haemoglobin levels is beneficial. This study will consider the indications for transfusion of blood and blood products, and will discuss common non-infectious complications associated with transfusion. Requirement of blood and blood component transfusions in children admitted in a tertiary care hospital and its related complications. OBJECTIVE To evaluate the pattern of transfusion requirement in children admitted in a tertiary care hospital and the frequency of transfusion related complications. METHODS Children of various age groups presenting with clinical profile like symptomatic anaemia, haemolytic anaemia, haematological malignancy, acute sickle cell

  10. Prevention and management of transfusion-induced alloimmunization: current perspectives

    Directory of Open Access Journals (Sweden)

    Hauck-Dlimi B

    2014-08-01

    Full Text Available Barbara Hauck-Dlimi, Susanne Achenbach, Julian Strobel, Reinhold Eckstein, Robert Zimmermann Department of Transfusion Medicine and Haemostaseology, University Hospital Erlangen, Erlangen, Germany Abstract: Transfusion of blood components, transplantations, and exchange of blood between mother and child during pregnancy or at birth can lead to alloimmunization. Because of its clinical relevance, this review brings into focus alloimmunization against red blood cells, human platelet antigens, human leukocyte antigens, and human neutrophil antigens. In principle, an individual is able to develop antibodies after exposure to a nonautogenous antigen, but these cells actually induce alloimmunization only for a minority of patients. An individual producing alloantibodies after having contact with foreign antigens depends on various factors, such as genetic predisposition, underlying diseases, the patient's immune status, and clinical immune modulation. When alloimmunization has occurred, it could lead to problems for future transfusions or transplantations. Keywords: transfusion, alloimmunization, prevention

  11. Transfusion in critically ill children

    DEFF Research Database (Denmark)

    Secher, E L; Stensballe, J; Afshari, A

    2013-01-01

    Transfusion of blood products is a cornerstone in managing many critically ill children. Major improvements in blood product safety have not diminished the need for caution in transfusion practice. In this review, we aim to discuss the interplay between benefits and potential adverse effects...... of transfusion in critically ill children by including 65 papers, which were evaluated based on previously agreed selection criteria. Current practice on transfusing critically ill children is mainly founded on the basis of adult studies, common practices with cut-off values, and expert opinions, rather than...... evidence-based medicine. Paediatric patients have explicit physiological challenges and requirements to be addressed. Critically ill children often suffer from anaemia, have substantial iatrogenic blood loss with subsequent transfusions, and are at a higher risk of complications, often due to human errors...

  12. Detrimental effects of perioperative blood transfusion

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1995-01-01

    Evidence suggests that perioperative allogeneic blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative operation. This has been attributed to immunosuppression. Several authors have suggested that filtered whole blood and/or red...... cell concentrate, or leucocyte- and buffy coat-reduced red cells in artificial medium or their own plasma, may reduce postoperative immunosuppression. It was also anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown...... similar postoperative infectious complications and cancer recurrence and/or survival rates in patients receiving autologous blood donated before operation and those receiving allogeneic blood. Future studies should identify common risk factors associated with blood storage....

  13. Cardiac iron across different transfusion-dependent diseases

    OpenAIRE

    Wood, John C.

    2008-01-01

    Iron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as β-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with β-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex th...

  14. Fatores preditivos da transfusão de concentrado de hemácias em pacientes submetidos a cirurgias eletivas do aparelho digestivo: uma análise interinstitucional Predictive factors associated with packed red cell transfusions in patients submitted to elective surgery of the digestive tract: an inter-institutional analysis

    Directory of Open Access Journals (Sweden)

    Antonio Sergio Barcala Jorge

    2010-01-01

    Full Text Available O objetivo desse estudo foi compreender os fatores determinantes da prática transfusional de concentrado de hemácias em cirurgias eletivas do aparelho digestivo em quatro unidades hospitalares em Montes Claros, Minas Gerais, Brasil. Foi realizado um estudo descritivo, analítico e retrospectivo através do levantamento de dados em prontuários clínicos de quatro unidades hospitalares de onde foram catalogados os dados de pacientes a partir de junho de 2007 a dezembro de 2008, referentes às cirurgias citadas. Os resultados evidenciaram 81 casos, sendo 42% do gênero feminino e 58% do masculino. A idade média foi de 55,5 anos (±19,11 anos. As enfermidades de base reportadas mais comuns foram os processos neoplásicos (42%. Desses 81 pacientes, 38 (47% foram hemotransfundidos no pré-operatório imediato, 28 (18% foram transfundidos no transcirúrgico e 37 (45,7% no pós-operatório imediato. Na análise univariada houve diferenças entre a prática transfusional pré-cirúrgica interinstitucional. Na fase cirúrgica houve relação entre a prática transfusional com a citação de motivos, fator RH (Rhesus, prática institucional e doença de base. Na fase pós-cirúrgica não foram demonstradas relações. Em todas as fases, não houve associação da prática transfusional com os tipos de procedimentos cirúrgicos, com o índice ASA (American Society of Anesthesiology e valores de hemoglobina e hematócrito. Concluindo, esse estudo revelou que a prática transfusional foi heterogênea entre instituições hospitalares, careceu de valores laboratoriais específicos, relacionou-se com a patologia de base mas não com o tipo de procedimento cirúrgico e foi norteada pelo critério de escolha do profissional.The objective of this study was to understand the determinative factors for packed red cell transfusions in elective digestive tract surgeries in four hospital units in Montes Claros, Minas Gerais, Brazil. Retrospective analyses were

  15. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.

  16. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors....... The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content......-reduced PRP. The sVEGF accumulated significantly in WB, SAGM blood, and BCP pools, depending on the storage time. CONCLUSION: The sVEGF (isotype 165) appears to be present in various blood transfusion components, depending on storage time....

  17. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn;

    2014-01-01

    BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

  18. DIETARY PHYTOCHEMICALS INDUCE p53- AND CASPASE-INDEPENDENT CELL DEATH IN HUMAN NEUROBLASTOMA CELLS

    OpenAIRE

    Sukumari-Ramesh, Sangeetha; Bentley, J Nicole; Laird, Melissa D.; Singh, Nagendra; Vender, John R.; Dhandapani, Krishnan M.

    2011-01-01

    Neuroblastoma (NB) is the most prevalent pediatric solid tumor and a leading cause of cancer-related death in children. In the present study, a novel cytotoxic role for the dietary compounds, curcumin, andrographolide, wedelolactone, dibenzoylmethane, and tanshinone IIA was identified in human S-type NB cells, SK-N-AS and SK-N-BE(2). Mechanistically, cell death appeared apoptotic by flow cytometry; however, these effects proceeded independently from both caspase-3 and p53 activation, as asses...

  19. Role of RBCs alloimmunization in multiple transfused thalassaemia patients

    Directory of Open Access Journals (Sweden)

    Amita Sagar Patel

    2016-03-01

    Results: Out 50 patients of thalassemia major, 4 patients (8% developed red cell alloantibodies respectively. The red cell alloantibodies were against Rh, Kidd, Kell, Duffy, Lewis, MNS and P system. Results of this study (P value >0.05 indicate low frequency of RBCs alloimmunization. Conclusions: Low alloimmunization rate implies that there is homogeneity of red cell antigens in blood donors and recipients. RBCs alloantibody formation was not influenced by gender, age at start of transfusions and number of packed cells received. Already alloimmunized patients get benefits from leucodepleted packed cells. Specific recommendation given on routine pre-transfusion antibody screening to ensure safer transfusion. [Int J Res Med Sci 2016; 4(3.000: 822-828

  20. Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Yi Gao; Shuan Wang; Er-Wei Sun; Yu Wang; Zhi Zhang; Yi-Qiang Shan; Shi-Zheng Zhong

    2005-01-01

    AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation),Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors),with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA.Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data.RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in DexSpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P = 0.000), control (P = 0.004), and Dex groups (P = 0.02). Results of

  1. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    Science.gov (United States)

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

  2. Transfusion practices and infectious risks.

    Science.gov (United States)

    Shander, Aryeh; Lobel, Gregg P; Javidroozi, Mazyar

    2016-06-01

    Transfusion-transmitted infections remain among the most-feared complications of allogeneic blood transfusion. Thanks to several strategies including donor screening and deferral, blood testing and pathogen inactivation, their risks have reached all-time low levels, particularly in developed nations. Nonetheless, new and emerging infections remain a threat that is likely to exacerbate in the coming years with continued globalization and climate change. More effective strategies of pathogen inactivation and more vigilant horizon screening are hoped to abate the risk. Additionally, allogeneic transfusion has repeatedly been shown to be associated with worsening of outcomes in patients, including the documented increased risk of infections (often nosocomial) in recipients of transfusions. The underlying mechanism is likely to be related to immunosuppressive effects of allogeneic blood, iron content, and bacterial contamination. This issue is best addressed by more judicious and evidence-based use of allogeneic blood components to ensure the potential benefits outweigh the risks. PMID:26959944

  3. Implementation of Mass Transfusion Protocol in the Outpatient Operating Room Setting: A Case Study.

    Science.gov (United States)

    Robins, Holly-May; Warner, Brenda

    2015-06-01

    The current definition of massive transfusion is replacement of 5 U of packed red blood cells in 3 hours because of uncontrolled hemorrhage or replacement of the entire blood volume within a 24-hour period. The prompt activation of a transfusion protocol can quickly restore hemodynamic stability. Effective teamwork and communication is critical for a favorable patient outcome. This case study demonstrates the effectiveness of using a massive transfusion protocol in an outpatient setting. PMID:26137761

  4. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites.

    Science.gov (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon

    2008-12-01

    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  5. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. PMID:26976217

  6. Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells.

    Science.gov (United States)

    Yoffe, Yael; David, Maya; Kalaora, Rinat; Povodovski, Lital; Friedlander, Gilgi; Feldmesser, Ester; Ainbinder, Elena; Saada, Ann; Bialik, Shani; Kimchi, Adi

    2016-09-01

    Multiple transcriptional and epigenetic changes drive differentiation of embryonic stem cells (ESCs). This study unveils an additional level of gene expression regulation involving noncanonical, cap-independent translation of a select group of mRNAs. This is driven by death-associated protein 5 (DAP5/eIF4G2/NAT1), a translation initiation factor mediating IRES-dependent translation. We found that the DAP5 knockdown from human ESCs (hESCs) resulted in persistence of pluripotent gene expression, delayed induction of differentiation-associated genes in different cell lineages, and defective embryoid body formation. The latter involved improper cellular organization, lack of cavitation, and enhanced mislocalized apoptosis. RNA sequencing of polysome-associated mRNAs identified candidates with reduced translation efficiency in DAP5-depleted hESCs. These were enriched in mitochondrial proteins involved in oxidative respiration, a pathway essential for differentiation, the significance of which was confirmed by the aberrant mitochondrial morphology and decreased oxidative respiratory activity in DAP5 knockdown cells. Further analysis identified the chromatin modifier HMGN3 as a cap-independent DAP5 translation target whose knockdown resulted in defective differentiation. Thus, DAP5-mediated translation of a specific set of proteins is critical for the transition from pluripotency to differentiation, highlighting the importance of cap-independent translation in stem cell fate decisions. PMID:27664238

  7. Autologous Blood Transfusion in Sports: Emerging Biomarkers.

    Science.gov (United States)

    Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas

    2016-07-01

    Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. PMID:27260108

  8. Occult Hepatitis B virus infection in previously screened, blood donors in Ile-Ife, Nigeria: implications for blood transfusion and stem cell transplantation

    OpenAIRE

    Amadin A. Olotu; Oyelese, Adesola O.; Salawu, Lateef; Rosemary A. Audu; Azuka P. Okwuraiwe; Aboderin, Aaron O.

    2016-01-01

    Background Hepatitis B virus (HBV) transmission through blood transfusion is reduced by screening for hepatitis B surface antigen (HBsAg). However this method cannot detect the presence of occult hepatitis B virus infection. This study sought to determine the prevalence of occult hepatitis B virus infection among blood donors in Ile-Ife, Nigeria. For the first time in Nigeria we employed an automated real-time PCR- method to investigate the prevalence of occult HBV in blood donors. Methods Bl...

  9. Transfusion interventions in critical bleeding requiring massive transfusion: a systematic review.

    Science.gov (United States)

    McQuilten, Zoe K; Crighton, Gemma; Engelbrecht, Sunelle; Gotmaker, Robert; Brunskill, Susan J; Murphy, Michael F; Wood, Erica M

    2015-04-01

    Critical bleeding (CB) requiring massive transfusion (MT) can occur in a variety of clinical contexts and is associated with substantial mortality and morbidity. In 2011, the Australian National Blood Authority (NBA) published patient blood management guidelines for CB and MT, which found limited high-quality evidence from which only 2 recommendations could be made. The aim of this systematic review (SR) was to update these guidelines and identify evidence gaps still to be addressed. A comprehensive search was performed for randomized controlled trials (RCTs) and SRs using MeSH index and free text terms in MEDLINE, the Cochrane Library (Issue 11, 2012), EMBASE, CINHAL, PUBMED, and the Transfusion Evidence Library up to July 15, 2014. The evidence was grouped according to 4 questions based on the original guideline relating to transfusion interventions: (1) effect of dose, timing, and ratio of red blood cells (RBCs) to component therapy on patient outcomes; (2) effect of RBC transfusion on patient outcomes; (3) effect of fresh frozen plasma, platelet, cryoprecipitate, fibrinogen concentrate, and prothrombin complex concentrate on patient outcomes; and (4) effect of recombinant activated factor VII (rFVIIa) on patient outcomes. From this search, 19 studies were identified: 6 RCTs and 13 SRs. Two of the RCTs were pilot/feasibility studies, 3 were investigating rFVIIa, and 1 compared restrictive versus liberal RBC transfusion in upper gastrointestinal hemorrhage. Overall, limited new evidence was identified and substantial evidence gaps remain, particularly with regard to the effect of component therapies, including ratio of RBC to component therapies, on patient outcomes. Clinical trials to address these questions are required. PMID:25716645

  10. Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Ira O Racoma

    Full Text Available Glioblastoma is the most aggressive and common type of malignant brain tumor in humans, with a median survival of 15 months. There is a great need for more therapies for the treatment of glioblastoma. Naturally occurring phytochemicals have received much scientific attention because many exhibit potent tumor killing action. Thymoquinone (TQ is the bioactive compound of the Nigella sativa seed oil. TQ has anti-oxidant, anti-inflammatory and anti-neoplastic actions with selective cytotoxicity for human cancer cells compared to normal cells. Here, we show that TQ selectively inhibits the clonogenicity of glioblastoma cells as compared to normal human astrocytes. Also, glioblastoma cell proliferation could be impaired by chloroquine, an autophagy inhibitor, suggesting that glioblastoma cells may be dependent on the autophagic pathway for survival. Exposure to TQ caused an increase in the recruitment and accumulation of the microtubule-associated protein light chain 3-II (LC3-II. TQ also caused an accumulation of the LC3-associated protein p62, confirming the inhibition of autophagy. Furthermore, the levels of Beclin-1 protein expression were unchanged, indicating that TQ interferes with a later stage of autophagy. Finally, treatment with TQ induces lysosome membrane permeabilization, as determined by a specific loss of red acridine orange staining. Lysosome membrane permeabilization resulted in a leakage of cathepsin B into the cytosol, which mediates caspase-independent cell death that can be prevented by pre-treatment with a cathepsin B inhibitor. TQ induced apoptosis, as determined by an increase in PI and Annexin V positive cells. However, apoptosis appears to be caspase-independent due to failure of the caspase inhibitor z-VAD-FMK to prevent cell death and absence of the typical apoptosis related signature DNA fragmentation. Inhibition of autophagy is an exciting and emerging strategy in cancer therapy. In this vein, our results describe a

  11. Enhancing Transfusion Safety: Nurse’s Role

    Directory of Open Access Journals (Sweden)

    Kyriazi Vasiliki

    2011-01-01

    Full Text Available Background: Despite strict clinical measures, there are distinct steps in transfusion process which require acute attention.The nurse is responsible for insuring that the right unit is administered to the right patient. Knowledge of risks is essential toadminister and monitor transfusions safely.Aim: This study summarizes the available data concerning transfusion adverse events and provides theoretical and technicalaspects for improving transfusion practice.Methodology: A systematic review in PubMed, MedLine and MDConsult database was conducted. The research limitsincluded English texts, referring to transfusion risks and technological means aiming at transfusion safety.Results: Blood transfusion is a medical intervention that saves lives and improves the quality of life. The regulations forensuring the availability and assuring the quality of the blood component cannot avoid transfusion errors, placing patients atrisk. Most frequent errors are attributed to practitioners involved in the clinical transfusion process. Based on reports toSerious Hazards of Transfusion (SHOT the risk of transfusion error is estimated at 1:16,500. Over the last years severalcommittees have recommended guidance for enhancing the safety of blood ordering and administration. Moreover, newtechnology like barcode on patient wristband manages to improve the performance in each step.Conclusion: Safe transfusion process depends on a series of linked processes and nurses should take specific measuresreferring to pre- and post-transfusion stage. Technological innovations could help patients in need of transfusion therapy.

  12. Transfusion reaction in a case with the rare Bombay blood group.

    Science.gov (United States)

    Shahshahani, Hayedeh Javadzadeh; Vahidfar, Mohamad Reza; Khodaie, Seyed Ali

    2013-01-01

    Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights the importance of both forward and reverse typing in ABO blood grouping and standard cross-matching and performing standard pretransfusion laboratory tests in hospital blood banks. PMID:23559776

  13. Transfusion reaction in a case with the rare Bombay blood group

    Directory of Open Access Journals (Sweden)

    Hayedeh Javadzadeh Shahshahani

    2013-01-01

    Full Text Available Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights the importance of both forward and reverse typing in ABO blood grouping and standard cross-matching and performing standard pretransfusion laboratory tests in hospital blood banks.

  14. Transfusion reaction in a case with the rare Bombay blood group.

    Science.gov (United States)

    Shahshahani, Hayedeh Javadzadeh; Vahidfar, Mohamad Reza; Khodaie, Seyed Ali

    2013-01-01

    Bombay phenotype is extremely rare in Caucasian with an incidence of 1 in 250,000. When individuals with the Bombay phenotype need blood transfusion, they can receive only autologous blood or blood from another Bombay blood group. Transfusing blood group O red cells to them can cause a fatal hemolytic transfusion reaction. In this study, we report a case with the rare Bombay blood group that was misdiagnosed as the O blood group and developed a hemolytic transfusion reaction. This highlights the importance of both forward and reverse typing in ABO blood grouping and standard cross-matching and performing standard pretransfusion laboratory tests in hospital blood banks.

  15. Size-independent symmetric division in extraordinarily long cells

    NARCIS (Netherlands)

    N. Pende; N. Leisch; H.R. Gruber-Vodicka; N.R. Heindl; J. Ott; T. den Blaauwen; S. Bulgheresi

    2014-01-01

    Two long-standing paradigms in biology are that cells belonging to the same population exhibit little deviation from their average size and that symmetric cell division is size limited. Here, ultrastructural, morphometric and immunocytochemical analyses reveal that two Gammaproteobacteria attached t

  16. Cell volume and membrane stretch independently control K+ channel activity

    DEFF Research Database (Denmark)

    Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L;

    2009-01-01

    A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch....... To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current...... was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude...

  17. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    Science.gov (United States)

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  18. Curcumin induces apoptosis-independent death in oesophageal cancer cells.

    LENUS (Irish Health Repository)

    O'Sullivan-Coyne, G

    2009-10-06

    Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038\\/sj.bjc.6605308 www.bjcancer.com.

  19. Curcumin induces apoptosis-independent death in oesophageal cancer cells.

    LENUS (Irish Health Repository)

    O'Sullivan-Coyne, G

    2012-01-31

    BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

  20. Detection of alloimmunization to ensure safer transfusion practice

    Directory of Open Access Journals (Sweden)

    Rashmi Sood

    2013-01-01

    Full Text Available Background: Serological safety is an integral part of overall safety for blood banks. Emphasis is on the use of routinue Red Blood Cell (RBC antibody screen test, at set time intervals, to reduce risks related to alloantibodies. Also emphasis is on importance of issuing antigen negative blood to alloantibody positive patients. Effect of using leucodepleted blood on the rate of alloimmunization is highlighted. The concept of provision of phenotypically matched blood is suggested. Materials and Methods: Antibody screen test is important to select appropriate blood for transfusion. Repeat antibody screen testing, except if time interval between the earlier and subsequent transfusion was less than 72 hours, followed by antibody identification, if required, was performed in patients being treated with repeat multiple blood transfusions. Between February 2008 and June 2009, repeat samples of 306 multi-transfused patients were analyzed. Search for irregular antibodies and reading of results was conducted using RBC panels (three-cell panel of Column Agglutination Technology (CAT and two cell panel of the Solid Phase Red Cell Adherence Technology (SPRCAT. Specificities of antibodies were investigated using appropriate panels, 11 cell panel of CAT and 16 cell panel of SPRCA. These technologies, detecting agglutination in columns and reactions in solid phase, evaluate the attachment of irregular incomplete antibody to antigen in the first phase of immunological reaction more directly and hence improve the reading of agglutination. Three to four log leuco reduced red blood cells were transfused to patients in the study using blood collection bags with integral filters. Results: Alloimmunization rate of 4.24% was detected from 306 multiply transfused patients tested and followed up. The Transfusion therapy may become significantly complicated. Conclusion: Red cell antibody screening and identification and subsequent issue of antigen negative blood have a

  1. SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

    OpenAIRE

    Gulbransen, Brian; Silver, Wayne; Finger, Tom

    2008-01-01

    Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout m...

  2. Digoxin elimination by exchange transfusion.

    Science.gov (United States)

    Rosegger, H; Zach, M; Gleispach, H; Beitzke, A

    1977-02-21

    The report covers four cases presenting simultaneous indications for digitalisation and exchange transfusions. Intravenous administration of digoxin was followed: 1. by monitoring of the behaviour of the plasma digoxin level; 2. by determination of the total amount of glycoside eliminated by the blood exchange. Particular attention was paid to the effect of the delay between injection and exchange transfusion on the amount of digoxin eliminated. All four cases showed moderate falls in plasma levels. The amounts of digoxin eliminated by exchange transfusion were in reverse relationship to the delay between administration of digoxin and the blood exchange. At no time did the eliminated fraction exceed 5% of the total amount present in the body. PMID:837948

  3. Transfusion practice and complications after laparotomy - an observational analysis of a randomized clinical trial

    DEFF Research Database (Denmark)

    Nielsen, Kamilla; Meyhoff, C S; Johansson, P I;

    2012-01-01

    Background  Transfusion of allogeneic red blood cells (RBC) may be associated with side effects. This study aimed to assess whether an association could be detected between transfusion practice and the occurrence of complications after laparotomy. Study design and methods  This study is an observ...

  4. Pressure-aided transfusion of platelets: does it affect the platelets?

    DEFF Research Database (Denmark)

    Fischer-Nielsen, Anne; Stissing, Trine; Maansson, Charlotte;

    2010-01-01

    In massively bleeding patients, pressure infusers are used for transfusion of red blood cells and plasma but not for platelets (PLTs) due to an assumed negative effect on the PLTs. This study examined whether pressure-aided in vitro transfusion affected the number, activation state, and/or function...

  5. Transfusion Support of the Transplant Patient

    OpenAIRE

    Nisbet-Brown, Eric

    1988-01-01

    Organ transplant has become a much more common procedure in recent years. Data suggest that blood transfusions prior to transplant can affect allograph survival. The author discusses blood transfusion in kidney and liver transplantation.

  6. Precautions and Adverse Reactions during Blood Transfusion

    Science.gov (United States)

    ... fever and need another transfusion may be given acetaminophen before the next transfusion. Allergic reactions Symptoms of an allergic reaction include itching, a widespread rash, swelling, dizziness, and headache. Less common symptoms are breathing difficulties, ...

  7. Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes.

    Science.gov (United States)

    Cowan, Cameron S; Abd-El-Barr, Muhammad; van der Heijden, Meike; Lo, Eric M; Paul, David; Bramblett, Debra E; Lem, Janis; Simons, David L; Wu, Samuel M

    2016-02-01

    Rod pathways are a parallel set of synaptic connections which enable night vision by relaying and processing rod photoreceptor light responses. We use dim light stimuli to isolate rod pathway contributions to downstream light responses then characterize these contributions in knockout mice lacking rod transducin-α (Trα), or certain pathway components associated with subsets of rod pathways. These comparisons reveal that rod pathway driven light sensitivity in retinal ganglion cells (RGCs) is entirely dependent on Trα, but partially independent of connexin 36 (Cx36) and rod bipolar cells. Pharmacological experiments show that rod pathway-driven and Cx36-independent RGC ON responses are also metabotropic glutamate receptor 6-dependent. To validate the RGC findings in awake, behaving animals we measured optokinetic reflexes (OKRs), which are sensitive to changes in ON pathways. Scotopic OKR contrast sensitivity was lost in Trα(-/-) mice, but indistinguishable from controls in Cx36(-/-) and rod bipolar cell knockout mice. Mesopic OKRs were also altered in mutant mice: Trα(-/-) mice had decreased spatial acuity, rod BC knockouts had decreased sensitivity, and Cx36(-/-) mice had increased sensitivity. These results provide compelling evidence against the complete Cx36 or rod BC dependence of night vision's ON component. Further, the findings suggest the parallel nature of rod pathways provides considerable redundancy to scotopic light sensitivity but distinct contributions to mesopic responses through complicated interactions with cone pathways. PMID:26718442

  8. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  9. Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Aliccia Bollig-Fischer

    Full Text Available Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF10A cells to an insulin-independent phenotype. Analysis of the effects of various concentrations of insulin and/or IGF-I on proliferation of MCF10A cells demonstrated that some of the effects of insulin were independent from those of IGF-I, suggesting that oncogene over expression drives a true insulin-independent proliferative phenotype. To test this hypothesis, we examined metabolic functions of insulin signaling in insulin-dependent and insulin-independent cells. HER2 over expression in MCF10A cells resulted in glucose uptake in the absence of insulin at a rate equal to insulin-induced glucose uptake in non-transduced cells. We found that a diverse set of oncogenes induced the same result. To gain insight into how HER2 oncogene signaling affected increased insulin-independent glucose uptake we compared HER2-regulated gene expression signatures in MCF10A and HER2 over expressing MCF10A cells by differential analysis of time series gene expression data from cells treated with a HER2 inhibitor. This analysis identified genes specifically regulated by the HER2 oncogene, including VAMP8 and PHGDH, which have known functions in glucose uptake and processing of glycolytic intermediates, respectively. Moreover, these genes specifically implicated in HER2 oncogene-driven transformation are commonly altered in human breast cancer cells. These results highlight the diversity of oncogene effects on cell regulatory pathways and the importance of oncogene-driven metabolic transformation in breast cancer.

  10. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells. PMID:18469090

  11. Clinical Application of Recombinant Human Erythropoietin in Red Blood Cell Transfusion in Perioperative Surgery%重组人促红素在外科围手术期红细胞动员的临床应用

    Institute of Scientific and Technical Information of China (English)

    于萍; 张婕

    2011-01-01

    The clinical application of recombinant human erythropoietin in red blood cell transfusion in perioperative surgery is reviewed, which indicates that recombinant human erythropoietin can obviously increase the levels of reticulocyte(Ret), hemoglobin(Hb) and hematocfit(Ht), rapidly improve anaemia, reduce blood transfusion requirements with fewer side effects, hence, it is a safe and effective drug for perioperative patients.%将重组人促红素在外科围手术期红细胞动员的国内外临床应用情况进展做一综述.临床研究结果表明,重组人促红素注射液可明显升高网织红细胞(Pet)、血红蛋白(Hb)、红细胞压积(Ht),迅速纠正贫血,减少输血,不良反应较少,是手术患者进行术前红细胞动员的安全有效药物.

  12. The beneficial effect of donor-specific transfusions: a review of existing explanations and a new hypothesis based on a relatively unapplied theory of T cell immunoregulation. A regulatory hypothesis in progress...

    Science.gov (United States)

    Wendel, T D

    2000-06-01

    The mechanism by which donor specific transfusions protect a graft from the recipient's immune system is unknown. It is likely that this beneficial mechanism is a subset or distinct exhibition of the general rules governing the regulation of the immune system. This phenomenon provides a strong framework for investigation of immune regulation, considering its potential consanguinity to immune regulation, that it is a paradox representing a manifestation of regulatory rules, and that it provides a wealth of clinical experience and experimentation from which to make inferences. Vital in any exploration of immune regulation, is the promise held in reducing the immune system to its chief elemental regulatory mechanisms and interactions. Strangely, the majority of this consequential work may have already been accomplished by Gershon, Green and colleagues with their elegant demarcation of T cell regulation into suppressor and contrasuppressor pathways. The practical and theoretical implications of this discovery seem to be, for the most part, ignored by mainstream immunology. It is doubtful, based on the quality and quantity of their work, or confirming work by other laboratories that they were inaccurate in their findings. It remains a horrible waste that their discoveries are not in immunology's pantheon of hallowed discoveries and are little used. With all this kept in mind, a comprehensive hypothesis of regulation was put together based mainly on Gershon's portrait of the suppressor and contrasuppressor pathways' contributions to immune regulation and experimentation surrounding the unsolved paradox of donor specific transfusions. PMID:10867743

  13. Direct antiglobulin test positivity in multi-transfused thalassemics

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    Ashish Jain

    2016-01-01

    Full Text Available Introduction: Red cell allo- and auto-immunization is a well recognized problem in multi-transfused thalassemic patients. We conducted this study on 301 multi-transfused thalassemic patients under the Thalassemia Transfusion Programme of Advanced Pediatric Centre of PGIMER. Aims and Objectives: The study was designed to determine the frequency of alloimmunization and autoimmunization in multi-transfused thalassemic patients and to establish the specificity of alloantibody to red cell antigens, if alloimmunization is detected. Materials and Methods: The antibody screening was performed by the conventional tube technique using commercially available three cell screening panel (Diamed Switzerland by saline, low ionic strength solution (LISS and albumin indirect antiglobulin test (IAT. Samples with alloantibodies were then tested with red cell identification panel to determine the alloantibody specificity. Autoantibody screening was performed by direct antiglobulin test (DAT during pre-transfusion testing. Results: Of the 301 patients, 52 (17.28% were found to have antibodies (-allo and –autoantibodies. A total of 11 red cell alloantibodies were detected in 10 patients and the specificities were anti-Kell in 6(54.5%, anti-D in 2(18.2%, anti-c in 1(9.1% and a combination of anti-E (9.1% and anti-Jkb in 1 (9.1% patients. DAT was positive in 48 (15.9% patients. The frequency of autoantibody was significantly higher in alloimmunized group as compared to non-alloimmunized group (60% V/s 14.4%. Also, the pre-transfusion hemoglobin was significantly lower in the immunized group (8.5 gm/dl V/s 9.0 gm/dl; p=0.03 than the non-immunized group. Conclusion: Based on these observations, we suggest antigen typing of all thalassemia major patients for ABO, Rh and Kell antigens before initiating transfusion therapy. Also, screening for allo- and auto-antibodies at regular intervals should be done prior to each transfusion.

  14. Blood transfusion trends in obstetrics at the Federal Teaching Hospital in Abakaliki, South-East Nigeria

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    Lawani OL

    2013-07-01

    Full Text Available Osaheni L Lawani,1 Chukwuemeka A Iyoke,2 Azubuike K Onyebuchi1 1Department of Obstetrics and Gynecology, Federal Teaching Hospital, Ebonyi State, Nigeria; 2Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Enugu State, Nigeria Background: Obstetric hemorrhage has been repeatedly implicated as a leading cause of maternal mortality in Nigeria, yet there are very few studies that evaluate the practice of blood transfusion in obstetrics as a life saving measure. Objectives: The aim of this study was to evaluate the practice of obstetric blood transfusion, the mean decision-transfusion interval, and the outcome in parturients who had blood transfusions. Methods: This was a prospective descriptive study conducted at the Federal Teaching Hospital, Abakaliki, South-East Nigeria, between 1st January, 2012 and 31st December, 2012. Statistical analysis was done using SPSS version 15.0 for Windows. Results: Out of 151 parturients who received blood transfusion, 141/151 (97.4% were knowledgeable about blood transfusion, while only 10/151 (2.6% had no knowledge of it. The hospital was the source of information for 120/151 (80.8% of the participants. Blood transfusion rate was 7.04% of all parturients. The mean decision-transfusion interval was 12.0 ± 4.3 hours. All participants were transfused with either whole blood or sedimented cells. The mean number of blood units transfused was 1.77 ± 0.93 units. The indications for transfusion were: anemia, 109/151 (72.2%; shock, 13/151 (8.6%; postpartum hemorrhage, 23/151 (15.2%; antepartum hemorrhage, 6 (4%. Six (4% women died; mortality was due to renal failure in 3/6 (50% and disseminated intravascular coagulopathy in 3/6 (50%. These deaths were due to delays and difficulty in securing blood for transfusion, while those who got transfused on time were salvaged with minimal morbidity, 21/151 (14%, or with no morbidity, 130/151 (86%. Conclusion: Excessive blood loss and anemia still

  15. [Blood transfusion in emergency settings: French military health service experience].

    Science.gov (United States)

    Sailliol, A; Ausset, S; Peytel, E

    2010-12-01

    Blood transfusion is required in a number of emergency settings and the French military health service (FMHS) has issued specific guidelines for the treatment of war casualties. These guidelines take into account European standards and laws, NATO standards, and also public sentiment regarding transfusion. These guidelines reflect a determination to control the process and to avoid the improvisation frequently associated with wartime transfusion. The evolution in warfare (terrorism and bombing more frequent than gunshot) and the wide use of body armor have deeply changed the clinical presentation of war injuries. These now involve the extremities in 80% of cases, with extensive tissue damage and heavy blood loss. The FMHS recommends that war casualties with hemorrhagic shock be brought quickly to a medical treatment facility (MTF) after first-line treatment applied through buddy aid or by medics. In the MTF, before an early Medevac, a damage control surgery will be performed, with resuscitation using freeze-dried plasma, red blood cells and fresh whole blood. The French military blood bank is responsible for blood product supply, training and medical advice regarding transfusion therapy during wartime, as well as hemovigilance. All transfusion therapy practices are periodically assessed but research on whole blood pathogen reduction is being conducted in order to reduce the residual infectious risk associated with this product. PMID:21051268

  16. Hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery

    Institute of Scientific and Technical Information of China (English)

    Mahdi; Najafi; David; Faraoni

    2015-01-01

    Although red blood cells(RBCs) transfusion is sometimes associated with adverse reactions,anemia could also lead to increased morbidity and mortality in highrisk patients. For these reasons,the definition of perioperative strategies that aims to detect and treat preoperative anemia,prevent excessive blood loss,and define "optimal" transfusion algorithms is crucial. Although the treatment with preoperative iron and erythropoietin has been recommended in some specific conditions,several controversies exist regarding the benefit-to-risk balance associated with these treatments. Further studies are needed to better define the indications,dosage,and route of administration for preoperative iron with or without erythropoietin supplementation. Although restrictive transfusion strategies in patients undergoing cardiac surgery have been shown to effectively reduce the incidence and the amount of RBCs transfusion without increase in side effects,some high-risk patients(e.g.,symptomatic acute coronary syndrome) could benefit from higher hemoglobin concentrations. Despite all efforts made last decade,a significant amount of work remains to be done to improve hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery.

  17. Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Background: Allogeneic blood transfusion-induced immunomodulation (TRIM) and its adverse effect on the prognosis of patients treated surgically for cancer remain complex and controversial. However, the potential risk associated with allogeneic blood transfusion has heightened interest in the use of autologous blood transfusion. In the present study, the serum concentrations of neopterin, interferon-gamma (IFN-γ), T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and a possible association between these variables were investigated. The purpose was to further evaluate the effect of autologous versus allogeneic blood transfusion on immunological status in patients undergoing surgery for gastric cancer. Methods: Sixty ASA Ⅰ~Ⅱ(American Society of Anesthesiologists) patients undergoing elective radical resection for stomach cancer were randomly allocated to receive either allogeneic blood transfusion (n=30) or autologous blood transfusion (n=30). Serum concentrations of the neopterin, IFN-γ and T lymphocyte subsets in the recipients were measured before induction of anesthesia, after operation, and on the 5th postoperative day. Results: Both two groups, serum neopterin, IFN-γ, percentages of T-cell subsets (CD3+, CD4+), and CD4+/CD8+ ratio had significantly decreased after operation, but decreased more significantly in group H (receiving allogeneic blood transfusion) than those in group A (receiving autologous whole blood transfusion) (P<0.05). On the 5th postoperative day,serum neopterin, IFN-γ, CD3+, CD4+ T-cells, and CD4+/CD8+ ratio returned to the baseline values in group A. In contrast, the above remain decreasing in group H, where there were no significant relations between serum neopterin and IFN-γ. Conclusion:Perioperative surgical trauma and stress have an immunosuppressive impact on gastric cancer patients. Allogeneic blood transfusion exacerbates the impaired immune response. Autologous blood transfusion might be significantly beneficial for

  18. Cell Wall Invertase Promotes Fruit Set under Heat Stress by Suppressing ROS-Independent Cell Death.

    Science.gov (United States)

    Liu, Yong-Hua; Offler, Christina E; Ruan, Yong-Ling

    2016-09-01

    Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop production, by using transgenic tomato (Solanum lycopersicum) with its CWIN inhibitor gene silenced and focusing on ovaries and fruits at 2 d before and after pollination, respectively. We found that the increase of CWIN activity suppressed LMHS-induced programmed cell death in fruits. Surprisingly, measurement of the contents of H2O2 and malondialdehyde and the activities of a cohort of antioxidant enzymes revealed that the CWIN-mediated inhibition on programmed cell death is exerted in a reactive oxygen species-independent manner. Elevation of CWIN activity sustained Suc import into fruits and increased activities of hexokinase and fructokinase in the ovaries in response to LMHS Compared to the wild type, the CWIN-elevated transgenic plants exhibited higher transcript levels of heat shock protein genes Hsp90 and Hsp100 in ovaries and HspII17.6 in fruits under LMHS, which corresponded to a lower transcript level of a negative auxin responsive factor IAA9 but a higher expression of the auxin biosynthesis gene ToFZY6 in fruits at 2 d after pollination. Collectively, the data indicate that CWIN enhances fruit set under LMHS through suppression of programmed cell death in a reactive oxygen species-independent manner that could involve enhanced Suc import and catabolism, HSP expression, and auxin response and biosynthesis. PMID:27462084

  19. Transplante autólogo de células-tronco hematopoiéticas sem uso de hemocomponentes Hematopoietic stem cell transplantation without the use of blood transfusions

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    Roberto L. Silva

    2006-06-01

    Full Text Available O transplante de células-tronco hematopoéticas (TCTH é terapia consolidada para tratamento de algumas doenças onco-hematológicas, e o suporte transfusional tem, tradicionalmente, sido fundamental para a realização do mesmo. Descrevemos um caso de paciente testemunha de Jeová, portadora de linfoma Hodgkin em terceira remissão parcial, que foi submetida a quimioterapia de altas doses com regime de condicionamento clássico (carmustina, etoposide, citarabina, melfalan e posterior infusão de células-tronco hematopoéticas sem o uso de hemocomponentes. A paciente apresentou toxicidade hematológica inerente ao procedimento e medidas clínicas de suporte tais como a utilização de eritropoetina, IL 11, antifibrinolítico, entre outras, foram utilizadas na tentativa de minimizar o risco de sangramento e anemia grave. O curso do transplante transcorreu sem complicações graves. Este caso demonstra que o transplante autólogo de células-tronco hematopoéticas sem o uso de hemocomponentes é factível em situações especiais, onde há clara expressão do desejo do paciente associado a condições clínicas favoráveis e acompanhamento médico especialista rigoroso.Hematopoietic stem cell transplantation (HSCT is standard therapy for the treatment of some hematological neoplasms and support with blood transfusions is considered essential for this procedure. Herein we describe the case of a Jeovah's witness who had Hodgkin's lymphoma in third partial remission and was submitted to high-dose chemotherapy using a classic conditioning regimen (carmustine, etoposide, cytarabine, melphalan with posterior infusion of autologous peripheral blood stem cells without the use of blood transfusions. The patient had the usual degree of hematological toxicity and was treated with clinical support measures, such as the use of erythropoietin, IL-11 and antifibrinolytics, with the goal of minimizing the risk of bleeding and serious anemia. The HSTC coursed

  20. Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    Energy Technology Data Exchange (ETDEWEB)

    Gemert, Martin J C van; Wijngaard, Jeroen P H M van den [Laser Centre and Department of Obstetrics, Laser Center, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Lopriore, Enrico [Division of Neonatology, Department of Pediatrics, Leiden University Medical Centre, Leiden (Netherlands); Pasman, Suzanne A; Vandenbussche, Frank P H A [Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Centre, Leiden (Netherlands)], E-mail: m.j.vangemert@amc.uva.nl

    2008-04-07

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others. (note)

  1. Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    International Nuclear Information System (INIS)

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others. (note)

  2. NOTE: Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

    Science.gov (United States)

    van Gemert, Martin J. C.; van den Wijngaard, Jeroen P. H. M.; Lopriore, Enrico; Pasman, Suzanne A.; Vandenbussche, Frank P. H. A.

    2008-04-01

    Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others.

  3. Blood genotyping for improved outcomes in chronic transfusion patients: current and future perspectives

    Directory of Open Access Journals (Sweden)

    Kutner JM

    2014-09-01

    Full Text Available Jose Mauro Kutner,1 Mariza Mota,1 Fabiana Conti,1 Lilian Castilho1,2 1Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 2Hemocentro Unicamp, Campinas, SP, Brazil Abstract: Blood transfusions are life sustaining in chronically transfused patients. However, certain complications, such as alloimmunization to red blood cells, can create challenges in the management of those patients. Routine phenotyping of blood recipients and the use of phenotype-matched blood units for transfusion have been useful to lower the occurrence of red cell alloantibodies in chronically transfused individuals. Nevertheless, extensive phenotyping is expensive, laborious, and cannot be performed in certain situations. The molecular understanding of blood groups has enabled the design of assays that may be used to better guide matched red blood cell transfusions. This review summarizes key findings related to red cell alloimmunization, the already identified and potential future benefits of blood group genotyping, and how molecular typing is being incorporated in the blood bank's routine to improve clinical and long-term outcomes in chronically transfused patients. Keywords: blood group genotyping, chronically transfused patients, platelet genotyping, RBC alloimmunization

  4. Cinnarizine and flunarizine improve the tumour radiosensitisation induced by erythrocyte transfusion in anaemic mice.

    Science.gov (United States)

    Wood, P. J.; Hirst, D. G.

    1989-01-01

    The ability of the calcium antagonists, cinnarizine and flunarizine, to enhance the radiosensitisation produced by the administration of an erythrocyte transfusion to anaemic, RIF-1 or SCCVII/St tumour bearing mice was determined. Erythrocyte transfusion alone increased radiation cell killing 10-fold in the RIF-1 tumour when given 0-4 h before X-rays. In contrast, the SCCVII/St showed only a 4-fold increase in sensitivity, apparent when erythrocytes were given 2-6 h before irradiation. The administration of 50 mg kg-1 cinnarizine or flunarizine to anaemic mice followed by erythrocyte transfusion 0 h before X-rays produced the same level of cell survival for both tumours, a 20-fold increase in cell killing for cinnarizine, and a 30-40-fold effect for flunarizine, even though at this time interval, the erythrocyte transfusion alone did not sensitise the SCCVII/St tumour to X-rays. Further investigations indicated, however, that the erythrocyte transfusion was necessary to achieve the sensitisation with the calcium antagonists, since giving flunarizine to anaemic mice alone only achieved a 4-fold increase in radiation cell killing. In addition, flunarizine given with erythrocyte transfusion 4 h before X-rays, in SCCVII/St, the optimal time for radiosensitisation in this tumour, did not further increase the level of cell killing achieved by flunarizine plus erythrocyte transfusion 0 h before X-rays. PMID:2803913

  5. Transfusion-related adverse reactions: From institutional hemovigilance effort to National Hemovigilance program

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    Rahul Vasudev

    2016-01-01

    Full Text Available Aims: In this study we have evaluated the various adverse reactions related to transfusion occurring in our institution as a pilot institutional effort toward a hemovigilance program. This study will also help in understanding the problems faced by blood banks/Transfusion Medicine departments in implementing an effective hemovigilance program. Materials and Methods: All the adverse reactions related to transfusion of whole blood and its components in various clinical specialties were studied for a period of 1 year. Any transfusion-related adverse event was worked up in accordance with guidelines laid down by the Directorate General of Health Services (DGHS and departmental standard operating procedures. Results: During the study period from November 1, 2011 to October 31, 2012, 45812 components were issued [30939 WB/PRBC; 12704 fresh frozen plasma (FFP; 2169 platelets]. Risk estimation per 1000 units of red cells (WB/PRBC transfused was estimated to be: 0.8 for febrile nonhemolytic transfusion reaction (FNHTR, 0.7 for allergic reaction, 0.19 for acute hemolytic transfusion reaction (AcHTR, 0.002 for anaphylactoid reactions, 0.1 for bacterial sepsis, and 0.06 for hypervolemia and hypocalcemia. 0.09 is the risk for delayed transfusion reaction and 0.03 is the risk for transfusion-related acute lung injury (TRALI. Risk estimate per 1,000 units of platelets transfused was estimated to be 1.38 for FNHTR, 1.18 for allergic reaction, and 1 in case of bacterial sepsis. Risk estimation per 1,000 units of FFP was estimated to be 0.15 for FNHTR and 0.2 for allergic reactions. Conclusions: Factors such as clerical checks at various levels, improvement in blood storage conditions outside blood banks, leukodepletion, better inventory management, careful donor screening, bedside monitoring of transfusion, and documentation of adverse events may decrease transfusion-related adverse events. Better coordination between transfusion specialists and various clinical

  6. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川

    2003-01-01

    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  7. The aging human recipient of transfusion products.

    Science.gov (United States)

    Nydegger, Urs E; Luginbühl, Martin; Risch, Martin

    2015-06-01

    In this review the different mechanisms of aging and frailty such as DNA defects due to impaired DNA repair, inflammatory processes, disturbances of oxidative phosphorylation are discussed together with mechanisms of cell repair. Components of blood plasma, such as the growth-differentiation protein GDF11, were shown to enhance neurogenesis and to improve the vasculature in the animal cortex and to rejuvenate muscle tissue. Advances in laboratory assays allow to identify plasma proteins that may affect tissue regeneration. This new knowledge from animal research might affect transfusion practice in geriatric patients in the future. Provided it can be translated and confirmed in human research, blood products might no longer be considered only as oxygen carriers or drugs to improve hemostasis. In the present time blood transfusion (RBCs, plasma or platelets) should be directed by differentiated guidelines considering not only cut-off values of hemoglobin, platelet count or coagulation but also old age-specific biologic variation, comorbidities and the clinical context e.g. of bleeding. PMID:25921506

  8. Transfusion-transmitted parasitic infections.

    Science.gov (United States)

    Singh, Gagandeep; Sehgal, Rakesh

    2010-07-01

    The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas' disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply. PMID:20859503

  9. Transfusion-transmitted parasitic infections

    Directory of Open Access Journals (Sweden)

    Singh Gagandeep

    2010-01-01

    Full Text Available The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas′ disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply.

  10. Spleen size changes in children with homozygous. beta. -thalassaemia in relation to blood transfusion

    Energy Technology Data Exchange (ETDEWEB)

    Karpathios, Th.; Antypas, A.; Dimitriou, P.; Nicolaidou, P.; Fretzayas, A.; Thomaidis, Th.; Matsaniotis, N. (First Department of Paediatrics of Athens University, Aghia Sophia Children' s Hospital, Athens, Greece and Department of Pathologic Physiology, University of Athens, Athens, Greece)

    1982-01-01

    18 thalassaemic children, aged 3.5 to 13 years comprise our clinical material. In 14 of them, clinically elicited spleen markings, haematocrit, blood platelet count and red cell morphology were studied daily for a whole period between 2 transfusions. In 10 patients considerable changes in spleen size were noticed. According to our clinical observations the spleen size starts decreasing 1 to 3 d after blood transfusion up to the 10th posttransfusion day fluctuating thereafter to reach its maximum size again prior to the next blood transfusion. The decrease of spleen size was followed by an increase of haematocrit and blood platelet count and vice versa. 4 additional children were studied clinically only twice: prior to and 7 to 10 d after blood transfusion. A definite decrease of the spleen size following blood transfusion was observed. Spleen and liver sup(99m)Tc-sulfur colloid uptake was studied in 10 of the above children prior to and 7 to 10 d after blood transfusion. Statistically significant post-transfusion increase of the spleen uptake was demonstrated. Our findings suggest that (a) splenic size is relevant to blood volume sequestered in this organ, (b) splenic radioactive uptake increases with its post-transfusion reduction in size.

  11. Spleen size changes in children with homozygous β-thalassaemia in relation to blood transfusion

    International Nuclear Information System (INIS)

    18 thalassaemic children, aged 3.5 to 13 years comprise our clinical material. In 14 of them, clinically elicited spleen markings, haematocrit, blood platelet count and red cell morphology were studied daily for a whole period between 2 transfusions. In 10 patients considerable changes in spleen size were noticed. According to our clinical observations the spleen size starts decreasing 1 to 3 d after blood transfusion up to the 10th posttransfusion day fluctuating thereafter to reach its maximum size again prior to the next blood transfusion. The decrease of spleen size was followed by an increase of haematocrit and blood platelet count and vice versa. 4 additional children were studied clinically only twice: prior to and 7 to 10 d after blood transfusion. A definite decrease of the spleen size following blood transfusion was observed. Spleen and liver sup(99m)Tc-sulfur colloid uptake was studied in 10 of the above children prior to and 7 to 10 d after blood transfusion. Statistically significant post-transfusion increase of the spleen uptake was demonstrated. Our findings suggest that (a) splenic size is relevant to blood volume sequestrated int this organ, (b) splenic radioactive uptake increases with its post-transfusion reductin in size. (author)

  12. Effectiveness of Pooled Platelet Transfusion in Concordant and Discordant Groups among Dengue Patients

    Science.gov (United States)

    Chowdappa, Vijaya; Masamatti, Smita Surendra

    2016-01-01

    Introduction Dengue affects more than 50 million people per year and is one of the most common causes of severe thrombocytopaenia. Thrombocytopaenia is a common complication of dengue and other viral fevers apart from malaria, typhoid, leptospirosis, leukaemia and megaloblastic anaemia. A platelet count of homeopathic therapy, recipients of packed red cells on the same day of platelet transfusion and recipients of multiple platelet transfusions within 24 hours were excluded from the study. Results The median post transfusion platelet increments (PPI) and corrected count increments (CCI) at 4hour post transfusion were 25,000/μL (5,000-80,000/μL) and 18,000/μL (range 8,000/μL- 47,500/μL) respectively among the responders. Median PPI and CCI at 24 hours were 45,000/μL and 28,863/μL among the responders. The median CCI at 4 hour post transfusion among the non-responders was 850/μL and at 24hours was 1,425/μL. At 24 hours responders showed significantly higher PPI as compared to non responders. The average platelets transfused were 4units in case of responders and 8 units in case of non-responders. Conclusion ABO identical and compatible pooled platelet transfusions were more successful in increasing the post transfusion platelet counts as compared to ABO incompatible pooled platelets. PMID:27630853

  13. Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells

    International Nuclear Information System (INIS)

    Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite. We examined the ability of nontoxic concentrations of selenite to promote apoptosis and inhibit proliferation in carmustine-sensitized androgen-independent human prostate cancer cells. Androgen-dependent LNCaP cells exhibited a significant decrease in cell viability when exposed to nontoxic concentrations of selenite, whereas androgen-independent PC-3 and DU145 cells showed a significant decrease in cell viability only at higher concentrations. Treatment of PC-3 cells with a combination of nontoxic selenite and carmustine resulted in greater increases in cytotoxicity, reactive oxygen species generation, growth inhibition, apoptosis, and DNA double-strand breaks, with concomitant decreases in DNA synthesis, glutathione, glutathione reductase, and antiapoptotic proteins. Combination treatment with carmustine and selenite triggered caspase-dependent apoptosis in PC-3 cells, which was not apparent when these cells were treated with selenite or carmustine alone. Genotoxicity in normal prostate epithelial cells was completely absent in the combination treatment of carmustine and selenite. In addition, carmustine decreased the induction of DNA double strand breaks by high-dose selenite in normal prostate epithelial cells. This is the first study to demonstrate that a nontoxic dose of selenite, in combination with carmustine, significantly induces apoptosis and growth inhibition in androgen-independent

  14. Blood transfusion economics in Greece.

    Science.gov (United States)

    Kyriopoulos, J E; Michail-Merianou, V; Gitona, M

    1995-01-01

    This paper describes the organizational structure and the economic impact of blood donation and transfusion in Greece and discusses some alternative aspects of its financing and its costing policy. The cost of blood transfusion is rising in Greece and amounts to nearly 15 billion drachmas per year due to the constant increase in demand and consequently, the price of each unit of blood. The production and distribution of blood on national scale involves meeting the demand for 500.000 units. Blood is mostly given by the friends and relatives of patients (55%) and by voluntary blood donation (30%). Approximately 50% of the blood produced is used in surgery, 20% for cases of beta-thalassaemia, 10% for emergencies and 20% for internal medicine cases. The blood transfusion system is totally funded by the state budget and the value to users is free of charge. The way in which blood is collected and processed differs from one geographical area to another and the unit cost depends on the size of the department concerned, ranging from 60-150 $. The need to control costs and restrain expenditure, in conjunction with guarantees of sufficiency and quality, makes it essential that measures should be taken to introduce economies of scale and encourage competition among blood providers, for increased production, components preparation and rational usage of blood. The introduction of a costing policy becomes necessary in this effort to achieve cost-containment techniques. PMID:8581182

  15. Impact of Transfusion on Cancer Growth and Outcome.

    Science.gov (United States)

    Goubran, Hadi A; Elemary, Mohamed; Radosevich, Miryana; Seghatchian, Jerard; El-Ekiaby, Magdy; Burnouf, Thierry

    2016-01-01

    For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. There is also a need to consider validating preparation methods of blood components for so far ignored biological markers, such as microparticles and biological response modifiers. Meanwhile, blood component transfusions should be regarded as a personalized medicine, taking into careful consideration the status and specificities of the patient, rather than as a routine hospital procedure. PMID:27006592

  16. Hop/STI1 modulates retinal proliferation and cell death independent of PrPC

    International Nuclear Information System (INIS)

    Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrPC). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrPC dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 (α-STI1) blocked both ganglion cell and NBL cell death independent of PrPC. cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while α-STI1 increased proliferation in the developing retina, both independent of PrPC. We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrPC

  17. Accuracy of continuous noninvasive hemoglobin monitoring for the prediction of blood transfusions in trauma patients.

    Science.gov (United States)

    Galvagno, Samuel M; Hu, Peter; Yang, Shiming; Gao, Cheng; Hanna, David; Shackelford, Stacy; Mackenzie, Colin

    2015-12-01

    Early detection of hemorrhagic shock is required to facilitate prompt coordination of blood component therapy delivery to the bedside and to expedite performance of lifesaving interventions. Standard physical findings and vital signs are difficult to measure during the acute resuscitation stage, and these measures are often inaccurate until patients deteriorate to a state of decompensated shock. The aim of this study is to examine a severely injured trauma patient population to determine whether a noninvasive SpHb monitor can predict the need for urgent blood transfusion (universal donor or additional urgent blood transfusion) during the first 12 h of trauma patient resuscitation. We hypothesize that trends in continuous SpHb, combined with easily derived patient-specific factors, can identify the immediate need for transfusion in trauma patients. Subjects were enrolled if directly admitted to the trauma center, >17 years of age, and with a shock index (heart rate/systolic blood pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo Corporation, Irvine, CA) was applied, providing measurement of continuous non-invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration analyzed and conventional pulse oximetry photopletysmograph signals were continuously recorded. Demographic information and both prehospital and admission vital signs were collected. The primary outcome was transfusion of at least one unit of packed red blood cells within 24 h of admission. Eight regression models (C1-C8) were evaluated for the prediction of blood use by comparing area under receiver operating curve (AUROC) at different time intervals after admission. 711 subjects had continuous vital signs waveforms available, to include heart rate (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not increase AUROC for prediction of transfusion. The highest ROC was recorded for model C8 (age, sex, prehospital shock index, admission

  18. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  19. Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients

    Directory of Open Access Journals (Sweden)

    Hari Krishan Dhawan

    2014-01-01

    Full Text Available Background: The development of anti-red blood cell antibodies (both allo-and autoantibodies remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. Materials and Methods: The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d gel cards. Results: Eighteen patients out of total 319 patients (5.64% developed alloantibodies and 90 (28.2% developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042. Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C w = 9%, 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Conclusion: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen. Early institution of transfusion therapy after diagnosis is another means of decreasing

  20. [European Blood Alliance (EBA) and EuroNet TMS: what challenges for the transfusion of tomorrow?].

    Science.gov (United States)

    Folléa, G; de Wit, J; Rouger, P

    2011-04-01

    The primary mission of the European Blood Alliance (EBA) is to contribute to the safety and efficiency of the supply of blood products, cells and tissues, in developing an active network of blood establishments in Europe (25 countries). Its strategic objectives are to improve performance (through working groups and projects funded by the European Union), to engage in regulatory affairs (particularly at the European Commission level) to promote best practices and to facilitate a network to collect and share knowledge and experiences. The main objective of EuroNet TMS, combining the blood scientific societies from more than 30 countries in Europe, is to update and publish regularly, intended for policymakers, a White Book on the transfusion chain from donor to patient and probable or possible changes in the coming 5 years. Since 2008, EBA and EuroNet TMS actively collaborate on the drafting of the 2nd edition to be published in 2011. The two presidents jointly drafted the final chapter outlining the major issues of transfusion for tomorrow, summarized thereafter. Transfusion will still be useful for a long time and for reasons of safety and ethics the voluntary and unpaid donations, with non-profit blood establishments, will remain, the cornerstone of the supply of blood products. This renders crucial the continuous improvement of donor management and optimal blood use. On the regulatory side, after 5 years of implementation, EU directives must be independently evaluated and the Blood Guide of the Council of Europe should gradually become a regulatory standard. Finally, if a competition should be introduced for the blood products, it should be strictly regulated to prevent any threat to the security of their supply and quality for patients. PMID:21458349

  1. Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties.

    Science.gov (United States)

    Tong, Xinming; Yang, Fan

    2014-02-01

    Hydrogels have been widely used as artificial cell niche to mimic extracellular matrix with tunable properties. However, changing biochemical cues in hydrogels developed-to-date would often induce simultaneous changes in mechanical properties, which do not support mechanistic studies on stem cell-niche interactions. Here we report the development of a PEG-based interpenetrating network (IPN), which is composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner. The resulting IPN hydrogel allows independently tunable biochemical and mechanical properties, as well as stable and more homogeneous presentation of biochemical ligands in 3D than currently available methods. We demonstrate the potential of our IPN platform for elucidating stem cell-niche interactions by modulating osteogenic differentiation of human adipose-derived stem cells. The versatility of such IPN hydrogels is further demonstrated using three distinct and widely used polymers to form the mechanical network while keeping the biochemical network constant.

  2. Calcium-independent phospholipase A₂, group VIA, is critical for RPE cell survival

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vohra, Rupali; Westlund, Barbro S.;

    2014-01-01

    PURPOSE: To investigate the significance of calcium-independent phospholipase A₂, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. METHODS: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were...... treated with SI to induce cell death. Cells were transfected with an iPLA₂-VIA promoter-luciferase construct to evaluate the regulation of iPLA-VIA after exposure to SI. PCR analysis, western blot analysis, and activity assays were performed to evaluate the mRNA level, protein level, and activity levels...... of iPLA₂-VIA after SI exposure. Inhibitors of iPLA₂-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA₂-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against...

  3. Clinical Response and Transfusion Reactions of Sheep Subjected to Single Homologous Blood Transfusion

    Directory of Open Access Journals (Sweden)

    Rejane Santos Sousa

    2014-01-01

    Full Text Available Studies in relation to blood conservation and responses to transfusion are scarce for ruminants. We evaluated the clinical manifestations of sheep that received a single homologous transfusion of whole blood, focusing on transfusion reactions. Eighteen adult sheep were subjected to a single phlebotomy to withdraw 40% of the total blood volume, which was placed into CPDA-1 bags and then divided into G0, animals that received fresh blood, and G15 and G35, animals that received blood stored for 15 or 35 days, respectively. Clinical observations were recorded throughout the transfusion, whereas heart rate, respiratory rate, and rectal temperature were assessed at the following times: 24 hours after phlebotomy and before transfusion; 30 minutes, six, twelve, 24, 48, 72, and 96 hours and eight and 16 days after transfusion. All groups presented transfusion reactions, among which hyperthermia was the most frequent (50% of animals. Tachycardia occurred most frequently in the G35 animals (50% of them. During transfusion G35 animals presented more clinical manifestation (P<0.05. Transfusion of fresh or stored total blood improved the blood volume, but transfusion reactions occurred, demonstrating that a single transfusion of fresh or stored blood can cause inflammatory and febrile nonhemolytic transfusion reactions in sheep.

  4. Blood transfusion after total shoulder arthroplasty: Which patients are at high risk?

    Directory of Open Access Journals (Sweden)

    Abdurrahman Kandil

    2016-01-01

    Full Text Available Purpose: There are multiple reported risk factors and a wide range of reported blood transfusion rates for total shoulder arthroplasty (TSA. There are no evidence-based guidelines for blood transfusions in TSA patients. Materials and Methods: We utilized the Nationwide Inpatient Sample to analyze 51,191 patients undergoing TSA between 1998 and 2011. The purpose was to describe the incidence and identify the preoperative factors that are independently associated with blood transfusion after TSA. In addition, we studied the association of blood transfusions with certain variables such as length of stay (LOS, total charges, and payer status. Results: The blood transfusion rate in our study was 6.1%. There was no difference in the rate of blood transfusions over the study period (P < 0.001. In our logistic regression model, significant associations were found with increased age (odds ratio [OR] =1.03, white race (OR = 1.05, higher Charlson-Deyo score (OR = 1.12, presence of ischemic heart disease (OR = 1.24, blood loss anemia (OR = 1.65, female gender (OR = 1.94, presence of coagulation disorders (OR = 2.25, and presence of deficiency anemia (OR = 3.5. Patients receiving a blood transfusion had higher total charges, a longer hospital LOS, and were more likely to be Medicare payers (P < 0.001. Conclusions: Our study found five clinically significant risk factors for blood transfusions for TSA: female gender, ischemic heart disease, deficiency anemia, coagulation disorder, and blood loss anemia. Patients with these risk factors should be considered higher risk for requiring a blood transfusion after TSA and counseled appropriately. Level of Evidence: Level II, retrospective cohort study, prognostic study.

  5. Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation.

    Directory of Open Access Journals (Sweden)

    Christian Wulbrand

    Full Text Available Hypoxia is a central problem in tumor treatment because hypoxic cells are less sensitive to chemo- and radiotherapy than normoxic cells. Radioresistance of hypoxic tumor cells is due to reduced sensitivity towards low Linear Energy Transfer (LET radiation. High LET α-emitters are thought to eradicate tumor cells independent of cellular oxygenation. Therefore, the aim of this study was to demonstrate that cell-bound α-particle emitting (213Bi immunoconjugates kill hypoxic and normoxic CAL33 tumor cells with identical efficiency. For that purpose CAL33 cells were incubated with (213Bi-anti-EGFR-MAb or irradiated with photons with a nominal energy of 6 MeV both under hypoxic and normoxic conditions. Oxygenation of cells was checked via the hypoxia-associated marker HIF-1α. Survival of cells was analysed using the clonogenic assay. Cell viability was monitored with the WST colorimetric assay. Results were evaluated statistically using a t-test and a Generalized Linear Mixed Model (GLMM. Survival and viability of CAL33 cells decreased both after incubation with increasing (213Bi-anti-EGFR-MAb activity concentrations (9.25 kBq/ml-1.48 MBq/ml and irradiation with increasing doses of photons (0.5-12 Gy. Following photon irradiation survival and viability of normoxic cells were significantly lower than those of hypoxic cells at all doses analysed. In contrast, cell death induced by (213Bi-anti-EGFR-MAb turned out to be independent of cellular oxygenation. These results demonstrate that α-particle emitting (213Bi-immunoconjugates eradicate hypoxic tumor cells as effective as normoxic cells. Therefore, (213Bi-radioimmunotherapy seems to be an appropriate strategy for treatment of hypoxic tumors.

  6. Exchange transfusion in complicated pediatric malaria: A critical appraisal.

    Science.gov (United States)

    Barman, Himesh

    2015-04-01

    Complicated falciparum malaria is a killer disease resulting in high mortality in spite of appropriate treatment. Some workers have reported improved survival when adjunct exchange blood transfusion is included in the treatment modality while others opine against it. This review is an effort to address and critically appraise current evidence for the treatment mode for severe malaria. The literature was searched with a specified search strategy to identify reports of children who underwent exchange transfusion for severe malaria. Total 23 children who underwent exchange transfusion for severe falciparum malaria published by 9 authors were identified. Age ranged from 5 months to 16 years with a mean age of 6.4 years. The average preprocedure parasite index (PI) was 41.4% (95confidence interval [CI]; 31.2-51.4). The average blood volume exchanged was 118.6% (95% CI; 94.7-143) of the circulating blood volume. The average postexchange reduction in PI was 34.1% (95% CI; 25.4-42.8). Three out of 23 children encountered some complications. All the children survivedKeywords: Exchange blood transfusion, parasite index, pediatric Intensive Care Unit, red cell exchange, severe falciparum malaria.

  7. Exchange transfusion in complicated pediatric malaria: A critical appraisal

    Directory of Open Access Journals (Sweden)

    Himesh Barman

    2015-01-01

    Full Text Available Complicated falciparum malaria is a killer disease resulting in high mortality in spite of appropriate treatment. Some workers have reported improved survival when adjunct exchange blood transfusion is included in the treatment modality while others opine against it. This review is an effort to address and critically appraise current evidence for the treatment mode for severe malaria. The literature was searched with a specified search strategy to identify reports of children who underwent exchange transfusion for severe malaria. Total 23 children who underwent exchange transfusion for severe falciparum malaria published by 9 authors were identified. Age ranged from 5 months to 16 years with a mean age of 6.4 years. The average preprocedure parasite index (PI was 41.4% (95confidence interval [CI]; 31.2-51.4. The average blood volume exchanged was 118.6% (95% CI; 94.7-143 of the circulating blood volume. The average postexchange reduction in PI was 34.1% (95% CI; 25.4-42.8. Three out of 23 children encountered some complications. All the children survivedKeywords: Exchange blood transfusion, parasite index, pediatric Intensive Care Unit, red cell exchange, severe falciparum malaria.

  8. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  9. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Science.gov (United States)

    Jain, Shweta; Chodisetti, Sathi Babu; Agrewala, Javed N

    2011-01-01

    Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response. PMID:21674065

  10. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  11. Low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome:a report of 2 cases%小剂量地西他滨联合异基因造血干细胞分次输注治疗老年骨髓增生异常综合征转急性髓性白血病2例报告

    Institute of Scientific and Technical Information of China (English)

    李云双; 陈永升; 聂伟业; 黄琴; 孔祥敬; 尹晓林

    2015-01-01

    Objective To explore the efficay of low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion( micro transplantation) for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome ( MDS-AML) .Methods Two patients diagnosed as MDS-AML were treated with chemotherapy regimen of low-dose decitabine or decitabine combined with CAG(cytosine arabinoside+aclacinomycin) and micro transplantation.The donors were children of patients with human leukocyte antigen semi-matched.Peripheral blood stem cells from the donors were mobilized with granulocyte colony-stimulating factor and then collected. Patients transfused PBSC about 36 hours after the chemotherapy finished.The disease status,platelet levels,survival timeand side effects were observed.Re sults Two cases did not achieve complete response.The survival times of Case 1 and Case 2 were 2 months and 4 months respectively. The platelet level in Case 1 increased remarkably after treatment,and reached to the maximal level of 59 ×109/L.No platelet transfusion was observed in Case 1.In Case 2,the interval of platelet transfusion was prolonged,and the patient was gradually independent on platelet transfusions. No graft-versus-host disease occurred in the two patients.Conclusion For elderly patients with MDS-AML,low-dose decitabine combined with micro transplantation can not cure the disease,but can prolong the survival time,increase the level of platelet and improve the quality of life.%目的 观察小剂量地西他滨联合异基因造血干细胞分次输注(微移植)治疗老年骨髓增生异常综合征转急性髓性白血病( MDS-AML)的疗效. 方法 对2例确诊为MDS-AML患者分别予小剂量地西他滨或地西他滨联合CAG方案(阿糖胞苷+阿克拉霉素)化疗加微移植治疗,供者为人类白细胞抗原半相合的患者子女,采集重组人粒细胞集落刺激因子动员后的供者外周血

  12. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

    2013-05-10

    Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  13. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  14. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  15. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Curry, Merril C; Peters, Amelia A; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2013-05-10

    The mitochondrial calcium uniporter (MCU) transports free ionic Ca(2+) into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(2+) levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  16. GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells

    OpenAIRE

    Bondarenko, Alexander; Waldeck-Weiermair, Markus; Naghdi, Shamim; Poteser, Michael; Malli, Roland; Graier, Wolfgang F

    2010-01-01

    Background and purpose The glycerol-based lysophospholipid lysophosphatidylinositol (LPI) is an endogenous agonist of the G-protein-coupled receptor 55 (GPR55) exhibiting cannabinoid receptor-like properties in endothelial cells. To estimate the contribution of GPR55 to the physiological effects of LPI, the GPR55-dependent and -independent electrical responses in this cell type were investigated. Experimental approach Applying small interference RNA-mediated knock-down and transient overexpre...

  17. Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism.

    Science.gov (United States)

    Kim, Hun Sik; Kwon, Hyung-Joon; Kim, Gye Eun; Cho, Mi-Hyang; Yoon, Seung-Yong; Davies, Alexander J; Oh, Seog Bae; Lee, Heuiran; Cho, Young Keol; Joo, Chul Hyun; Kwon, Seog Woon; Kim, Sun Chang; Kim, Yoo Kyum

    2014-07-01

    The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance. PMID:24743513

  18. INFECTIOUS-DISEASE TESTING FOR BLOOD-TRANSFUSIONS

    NARCIS (Netherlands)

    DESFORGES, JF; ATHARI, F; COOPER, ES; JOHNSON, CS; LEMON, SM; LINDSAY, KL; MCCULLOUGH, J; MCINTOSH, K; ROSS, RK; WHITSETT, CF; WITTES, J; WRIGHT, TL

    1995-01-01

    Objective.-To provide physicians and other transfusion medicine professionals with a current consensus on infectious disease testing for blood transfusions. Participants.-A nonfederal, nonadvocate, 12-member consensus panel representing the fields of hematology, infectious disease, transfusion medic

  19. B cells contribute to MS pathogenesis through antibody-dependent and antibody-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Wilson HL

    2012-05-01

    Full Text Available Heather L Wilson1,21Vaccine and Infectious Disease Organization-International Vaccine Center, 2Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: For many years, central dogma defined multiple sclerosis (MS as a T cell-driven autoimmune disorder; however, over the past decade there has been a burgeoning recognition that B cells contribute to the pathogenesis of certain MS disease subtypes. B cells may contribute to MS pathogenesis through production of autoantibodies (or antibodies directed at foreign bodies, which unfortunately cross-react with self-antigens, through promotion of T cell activation via antigen presentation, or through production of cytokines. This review highlights evidence for antibody-dependent and antibody-independent B cell involvement in MS pathogenesis.Keywords: autoantibodies, antibody targets, clinically isolated MS, primary progressive MS, secondary progressive MS, relapsing and remitting MS, T cells, T regulatory cells

  20. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sunga [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of); Kim, Ki Mo [Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM), 305811, Daejeon (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301747 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Gangwon-do, 200701 (Korea, Republic of)

    2011-12-15

    Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specific features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer. -- Highlights: Black-Right-Pointing-Pointer We studied the mechanism which cordycepin-induced cell death association with

  1. SAP-Dependent and -Independent Regulation of Innate T Cell Development Involving SLAMF Receptors.

    Science.gov (United States)

    De Calisto, Jaime; Wang, Ninghai; Wang, Guoxing; Yigit, Burcu; Engel, Pablo; Terhorst, Cox

    2014-01-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B-cell responses. Additionally, the expression of SAP in double-positive thymocytes is mandatory for natural killer T (NKT) cells and, in mouse, for innate CD8(+) T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1 + 6](-/-) and Slamf[1 + 5 + 6](-/-) B6 mice have ~70% reduction of NKT cells compared to wild-type B6 mice. Unexpectedly, the proportion of innate CD8(+) T cells slightly increased in the Slamf[1 + 5 + 6](-/-) , but not in the Slamf[1 + 6](-/-) strain, suggesting that Slamf5 may function as a negative regulator of innate CD8(+) T cell development. Accordingly, Slamf5(-/-) B6 mice showed an exclusive expansion of innate CD8(+) T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7(-/-) strain showed an expansion of both splenic innate CD8(+) T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3(-/-) BALB/c mice, the proportions of thymic promyelocytic leukemia zinc finger (PLZF(hi)) NKT cells and innate CD8(+) T cells significantly increased in the SAP-independent Slamf8(-/-) BALB/c strain. In summary, these results show that NKT and innate CD8(+) T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8(+) T cells.

  2. SAP-independent and -dependent regulation of innate T cell development involving SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Jaime eDe Calisto

    2014-04-01

    Full Text Available Signaling lymphocytic activation molecule (SLAM-associated protein (SAP plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF of receptors, whose expression is essential for T, NK, and B cell responses. Additionally, the expression of SAP in double-positive (DP thymocytes is mandatory for natural killer T (NKT cells and, in mouse, for innate CD8+ T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1+6]-/- and Slamf[1+5+6]-/- B6 mice have an approximately 70% reduction of NKT cells compared to wild-type (WT B6 mice. Unexpectedly, the proportion of innate CD8+ T cells slightly increased in the Slamf[1+5+6]-/-, but not in the Slamf[1+6]-/- strain, suggesting that Slamf5 may function as a negative regulator of innate CD8+ T cell development. Accordingly, Slamf5-/- B6 mice showed an exclusive expansion of innate CD8+ T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7-/- strain showed an expansion of both splenic innate CD8+ T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3-/- BALB/c mice, the proportions of thymic PLZFhi NKT cells and innate CD8+ T cells significatively increased in the SAP-independent Slamf8-/- BALB/c strain. In summary, these results show that NKT and innate CD8+ T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8+ T cells.

  3. Evidence Based Studies in Clinical Transfusion Medicine

    NARCIS (Netherlands)

    A.J.G. Jansen (Gerard)

    2007-01-01

    textabstractAfter the introduction of blood component therapy in the 1960s, more and more attention is given to clinical transfusion medicine. Although blood transfusion is an important treatment in different clinical settings, there are still lack of much randomized clinical trials. Nowadays bloo

  4. [Blood transfusion: the challenges for tomorrow?].

    Science.gov (United States)

    Folléa, Gilles; Garraud, Olivier; Tiberghien, Pierre

    2015-02-01

    As any therapeutic means, blood transfusion requires regular evaluation, particularly for its indications, effectiveness and risks. The availability of randomized clinical trials, the evolution of the quality of blood components, and the economic constraints shared by all countries, all lead to rethink both transfusion therapy as a whole and the organization of the transfusion chain from donor to recipient. The main tools available to improve transfusion and the transfusion chain management are the following: programs of patient blood management (PBM) to optimize the use of blood products with a patient centred approach, blood supply management tools to improve the effectiveness and efficiency of the transfusion chain, donor management tools to adapt donor collections to the patients' needs in compliance with safety requirements for patients and donors, and coordination of these activities. A better understanding of these tools and their implementation will certainly be major challenges for transfusion medicine in the near future. Integrating these evolutions in regulations through the revision of the European Directives on blood and blood components (the review process is expected to be launched in 2015) should enroll them in the long term, for the benefit of patients, donors and all other stakeholders involved in the transfusion chain. PMID:25578549

  5. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Science.gov (United States)

    Modell, Joshua W; Kambara, Tracy K; Perchuk, Barrett S; Laub, Michael T

    2014-10-01

    Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage. PMID:25350732

  6. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Directory of Open Access Journals (Sweden)

    Joshua W Modell

    2014-10-01

    Full Text Available Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  7. A DNA damage-induced, SOS-independent checkpoint regulates cell division in Caulobacter crescentus.

    Science.gov (United States)

    Modell, Joshua W; Kambara, Tracy K; Perchuk, Barrett S; Laub, Michael T

    2014-10-01

    Cells must coordinate DNA replication with cell division, especially during episodes of DNA damage. The paradigm for cell division control following DNA damage in bacteria involves the SOS response where cleavage of the transcriptional repressor LexA induces a division inhibitor. However, in Caulobacter crescentus, cells lacking the primary SOS-regulated inhibitor, sidA, can often still delay division post-damage. Here we identify didA, a second cell division inhibitor that is induced by DNA damage, but in an SOS-independent manner. Together, DidA and SidA inhibit division, such that cells lacking both inhibitors divide prematurely following DNA damage, with lethal consequences. We show that DidA does not disrupt assembly of the division machinery and instead binds the essential division protein FtsN to block cytokinesis. Intriguingly, mutations in FtsW and FtsI, which drive the synthesis of septal cell wall material, can suppress the activity of both SidA and DidA, likely by causing the FtsW/I/N complex to hyperactively initiate cell division. Finally, we identify a transcription factor, DriD, that drives the SOS-independent transcription of didA following DNA damage.

  8. Cell adhesion molecules regulate contractile ring-independent cytokinesis in Dictyostelium discoideum

    Institute of Scientific and Technical Information of China (English)

    Akira Nagasaki; Masamitsu Kanada; Taro QP Uyeda

    2009-01-01

    To investigate the roles of substrate adhesion in cytokinesis, we established cell lines lacking paxiUin (PAXB) or vinculin (VINA), and those expressing the respective GFP fusion proteins in Dictyostelium discoideum. As in mammalian cells, GFP-PAXB and GFP-VINA formed focal adhesion-like complexes on the cell bottom, paxB cells in suspension grew normally, but on substrates, often failed to divide after regression of the furrow. The efficient cytokinesis of paxB cells in suspension is not because of shear forces to assist abscission, as they divided normally in static suspension culture as well. Double knockout strains lacking mhcA, which codes for myosin I1, and paxB or vinA displayed more severe cytokinetic defects than each single knockout strain. In mitotic wild-type cells, GFP-PAXB was diffusely distributed on the basal membrane, but was strikingly condensed along the polar edges in mitotic mhcA cells. These results are consistent with our idea that Dictyostelium displays two forms of cytokinesis, one that is contractile ringdependent and adhesion-independent, and the other that is contractile ring-independent and adhesion-dependent, and that the latter requires PAXB and VINA. Furthermore, that paxB cells fail to divide normally in the presence of substrate adhesion suggests that this adhesion molecule may play additional signaling roles.

  9. Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

    Directory of Open Access Journals (Sweden)

    Hinrich eAbken

    2013-11-01

    Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

  10. Regulation of the transferrin-independent iron transport system in cultured cells.

    Science.gov (United States)

    Kaplan, J; Jordan, I; Sturrock, A

    1991-02-15

    Mammalian cells accumulate iron via the binding of transferrin to high affinity surface receptors, or through a transferrin-independent pathway which involves the uptake of iron-organic anion chelates by a membrane-based transport system. Previously we determined that the transferrin-independent transport system was present on a wide variety of cultured cells (Sturrock, A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1990) J. Biol. Chem. 265, 3139-3145). In this communication we demonstrate that the transferrin-independent iron uptake system is regulated differently than the transferrin-mediated pathway. The activity of the transferrin-independent system was unaffected by changes in cellular growth rate, induction of DNA synthesis and cell division, or depletion of cellular iron. Exposure of cells to ferric or ferrous iron, however, resulted in a time-dependent increase in transport activity, due to a change in Vmax with no change in Km. Increased transport activity was seen in a variety of cultured cell types, occurred in the presence of cycloheximide, and persisted for hours after removal of iron. The ability of other transition metals to induce changes in transport, or to compete with iron for accumulation by the transferrin-independent uptake system, was critically dependent on the composition of the media in which the cells were incubated. Metals such as Cu2+ or Zn2+, but not Cd2+ or Mn2+, when dissolved in a balanced salt solution buffered with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, induced changes in the transferrin-independent iron transport system. The same metals which induced changes in transport were ineffective in media containing amino acids, ascorbate, or N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine. The Vmax of the transferrin-independent iron transport system was also elevated by increases in intracellular Ca2+. The effect of iron on transport activity, however, did not result from an iron-induced release of

  11. One size will never fit all: the future of research in pediatric transfusion medicine.

    Science.gov (United States)

    Josephson, Cassandra D; Mondoro, Traci Heath; Ambruso, Daniel R; Sanchez, Rosa; Sloan, Steven R; Luban, Naomi L C; Widness, John A

    2014-11-01

    There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and among transfusion medicine specialists regarding the small number of investigators and studies in the field of pediatric transfusion medicine (PTM). Accordingly, the objective of this article is to provide a snapshot of the clinical and translational PTM research considered to be of high priority by pediatricians, neonatologists, and transfusion medicine specialists. Included is a targeted review of three research areas of importance: (i) transfusion strategies, (ii) short- and long-term clinical consequences, and (iii) transfusion-transmitted infectious diseases. The recommendations by PTM and transfusion medicine specialists represent opportunities and innovative strategies to execute translational research, observational studies, and clinical trials of high relevance to PTM. With the explosion of new biomedical knowledge and increasingly sophisticated methodologies over the past decade, this is an exciting time to consider transfusion medicine as a paradigm for addressing questions related to fields such as cell biology, immunology, neurodevelopment, outcomes research, and many others. Increased awareness of PTM as an important, fertile field and the promotion of accompanying opportunities will help establish PTM as a viable career option and advance basic and clinical investigation to improve the health and wellbeing of children.

  12. Mass casualty events: blood transfusion emergency preparedness across the continuum of care.

    Science.gov (United States)

    Doughty, Heidi; Glasgow, Simon; Kristoffersen, Einar

    2016-04-01

    Transfusion support is a key enabler to the response to mass casualty events (MCEs). Transfusion demand and capability planning should be an integrated part of the medical planning process for emergency system preparedness. Historical reviews have recently supported demand planning for MCEs and mass gatherings; however, computer modeling offers greater insights for resource management. The challenge remains balancing demand and supply especially the demand for universal components such as group O red blood cells. The current prehospital and hospital capability has benefited from investment in the management of massive hemorrhage. The management of massive hemorrhage should address both hemorrhage control and hemostatic support. Labile blood components cannot be stockpiled and a large surge in demand is a challenge for transfusion providers. The use of blood components may need to be triaged and demand managed. Two contrasting models of transfusion planning for MCEs are described. Both illustrate an integrated approach to preparedness where blood transfusion services work closely with health care providers and the donor community. Preparedness includes appropriate stock management and resupply from other centers. However, the introduction of alternative transfusion products, transfusion triage, and the greater use of an emergency donor panel to provide whole blood may permit greater resilience.

  13. An attempt to induce transient immunosuppression pre-erythrocytapheresis in a girl with sickle cell disease, a history of severe delayed hemolytic transfusion reactions and need for hip prosthesis

    Directory of Open Access Journals (Sweden)

    Alessandro Cattoni

    2013-06-01

    Full Text Available We report on a case of delayed hemolytic transfusion reaction (DHTR occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn’t prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyper-bilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient’s general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis.

  14. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  15. Polarization independent beam fanning using a multi-domain liquid crystal cell.

    Science.gov (United States)

    Ren, Hongwen; Wu, Shin-Tson

    2009-07-01

    Polarization independent beam fanning using a multi-domain liquid crystal (LC) cell is demonstrated experimentally. In the neighboring domains, the LC directors are aligned in orthogonal directions. To prove concepts, two hybrid-aligned LC cells with four and six domains were fabricated. Applying a voltage across the LC layer will change the phase difference between the neighboring domains. When the phase difference is 2mpi (m is an integer), the LC cell will not disturb the incident beam. However, if the phase shift is (2m + 1)pi, the outgoing beam will fan out into several beams; the number of fanout beams is equal to the domain number. PMID:19582068

  16. Hepatic Cell Apoptosis Was Triggerred by HBx Accumulation and Independent on Verapamil

    Institute of Scientific and Technical Information of China (English)

    王海平; 陈孝平; 白祥军

    2004-01-01

    Summary: In order to studythe roles of HBx and calcium inhibitor verapamil in apoptosis of human normal hepatic cells, L02-off, a pTet-off stably integrated human hepatic cell line was established,in which HBx expression was tightly induced by Doxycycline. The effect of different amounts of HBx and verapamil on apoptosis of human normal hepatic cells was detected. The study showed that apoptosis was triggered by accumulation of intracellular HBx, while verapamil had no effects on the apoptotic process. It was concluded that apoptosis mediated by HBx was dose-dependent but calcium-independent.

  17. Independent regulation of tumor cell migration by matrix stiffness and confinement

    Science.gov (United States)

    Pathak, Amit; Kumar, Sanjay

    2012-01-01

    Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM). While the influence of ECM stiffness on cell migration, adhesion, and contractility has been extensively studied in 2D culture, extension of this concept to 3D cultures that more closely resemble tissue has proven challenging, because perturbations that change matrix stiffness often concurrently change cellular confinement. This coupling is particularly problematic given that matrix-imposed steric barriers can regulate invasion speed independent of mechanics. Here we introduce a matrix platform based on microfabrication of channels of defined wall stiffness and geometry that allows independent variation of ECM stiffness and channel width. For a given ECM stiffness, cells confined to narrow channels surprisingly migrate faster than cells in wide channels or on unconstrained 2D surfaces, which we attribute to increased polarization of cell-ECM traction forces. Confinement also enables cells to migrate increasingly rapidly as ECM stiffness rises, in contrast with the biphasic relationship observed on unconfined ECMs. Inhibition of nonmuscle myosin II dissipates this traction polarization and renders the relationship between migration speed and ECM stiffness comparatively insensitive to matrix confinement. We test these hypotheses in silico by devising a multiscale mathematical model that relates cellular force generation to ECM stiffness and geometry, which we show is capable of recapitulating key experimental trends. These studies represent a paradigm for investigating matrix regulation of invasion and demonstrate that matrix confinement alters the relationship between cell migration speed and ECM stiffness. PMID:22689955

  18. Effect of miR-296 on the Apoptosis of Androgen-independent Prostate Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Pei CHENG; Run-sheng LI; Biao-yang LIN; Wei-qun WANG; Yu-hua LI; Yan GUO; Wei LI

    2009-01-01

    Objective To investigate the miR-296's function in prostate carcinoma(PCa) cells. Methods In order to profile the miRNA expression in LNCaP cells, the cultured cells were stimulated with androgen after 48-h starvation, miRNA microarray analysis and Q-RT-PCR assay were performed. To characterize the effects of miR296 on PCa cells, CL-1 and PC-3 cells were transfected with miR-296 and antisense-miR-296, cell growth and apoptosis were then analyzed. Results The miR-296-5p expression was up-regulated by 2.22 folds in the CL-1 cells, which do not express significantly androgen receptor, than in LNCaP cells. Knockdown of miR-296-Sp induced apoptosis of CL-1 cells, but not LNCaP cells. However, knockdown of miR-296-Sp inhibited the growth rate of LNCaP cells cultured in absence of androgen. Conclusion MiR-296-5p could be irnportant for development of prostate cancer from androgen dependence to androgen independence.

  19. Autologous Transfusion in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Radmehr H

    2003-11-01

    Full Text Available Preoperative autologous blood donation is commonly used to reduce exposure to homologous blood transfusions among patients undergoing elective cardiac surgery. The aim of this study was to evaluate the effect of autologous transfusion on patients' hematocryte value, intra and postoperative blood loss, hospitalization time, the development of infective complications and other factors. Materials and Methods: Between June 2001 to April 2002, 208 patients were underwent cardiac surgery in cardiac surgery ward in Imam Khomeini Medical Center. One or more blood units donate from 104 Patients before cardiopulmonary bypass and heparin injection, and transfused to them after CPB and Protamin injection (autologous Group, group 1. 104 patients underwent cardiac surgery routinely (control group, group 2."nResults: Mean of age was 55.9±8.6 in group 1 and 56.6±9.3 in group 2 (P=NS. 73 male and 31 females were in group 1 and 79 males and 25 females were in group 2 (P=NS. Smoking, familial history, hyperlipidemia, diabetes mellitus, renal failure, hypertension, stroke, and history of myocardial infarction was similar in two groups."nSeverity of angina, urgency operation, number vessels disease, duration of cardiopulmonary bypass, duration of aortic cross clamp time, use of internal thoracic artery graft, and number of grafts was similar in both groups. Mean of bleeding post operation was 548 cc in group 1 and 803 cc in-group 2 (P=0.003. Bleeding that need to operation was 1.8% in group 1 and 8.6% in group 2 (P=0.002. Wound infection, mediastinitis, renal failure, ventilatory prolonged, stroke, need to Intra-aortic Balloon Pump (IABP, intraoperative bleeding, and hospital stay was similar in both groups. Mean of extubationt time was 10.2 hours in group 1 and 14.8 hours in group 2 (P=0.001."nConclusion: Preoperative and intra-operative donations are safe and continue to contribute uniquely to blood conservation, providing important options in comprehensive

  20. Enhanced adhesion of osteoblastic cells on polystyrene films by independent control of surface topography and wettability

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Seung Yun [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Kim, Eung-Sam [School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Jeon, Gumhye [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Choi, Kwan Yong, E-mail: kchoi@postech.ac.kr [School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of); Kim, Jin Kon, E-mail: jkkim@postech.ac.kr [National Creative Research Center for Block Copolymer Self-Assembly, Departments of Environmental Science and Engineering and Chemical Engineering, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of)

    2013-04-01

    We independently controlled surface topography and wettability of polystyrene (PS) films by CF{sub 4} and oxygen plasma treatments, respectively, to evaluate the adhesion and proliferation of human fetal osteoblastic (hFOB) cells on the films. Among the CF{sub 4} plasma-treated PS films with the average surface roughness ranging from 0.9 to 70 nm, the highest adhesion of hFOB cells was observed on a PS film with roughness of ∼ 11 nm. When this film was additionally treated by oxygen plasma to provide a hydrophilic surface with a contact angle less than 10°, the proliferation of bone-forming cell was further enhanced. Thus, the plasma-based independent modification of PS film into an optimum nanotexture for human osteoblast cells could be appplied to materials used in bone tissue engineering. Highlights: ► New approach based on plasma treatment to independently control the surface topography and wettability ► The adhesion of human fetal osteoblast (hFOB) was enhanced on a surface with an average roughness of ∼ 11 nm. ► The adhesion and proliferation of hFOB was maximized when nanotextured surface became highly hydrophilic.

  1. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

    Directory of Open Access Journals (Sweden)

    Kelly B McClellan

    2006-06-01

    Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

  2. B Cells Regulate CD4+ T cell Responses to Papain Following BCR-Independent Papain Uptake

    OpenAIRE

    Dwyer, Daniel F.; Woodruff, Matthew C.; Carroll, Michael C.; Austen, K. Frank; Gurish, Michael F.

    2014-01-01

    Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL4 expression by T cells in the popliteal lymph nodes (PLN) of mice following footpad immunization. Here we identify a novel, non-BCR mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing Inducible T cell Costimulator (ICOS) expression on CD4+ T cells and amplifying Th2 and T follicular helper induction. Antibody blockade...

  3. Nurses' perceptions of transfusion training: an evaluation.

    Science.gov (United States)

    Stout, Lynn

    Within Scottish hospitals transfusion education is mandatory for all staff involved in the process of transfusion. Currently two modes of delivery exist, face-to-face and e-learning. The researcher,a transfusion practitioner, wished to evaluate the perceptions of registered nurses within her local children's hospital to the transfusion education available. The aim of the evaluation was to ascertain whether there were perceived benefits, whether expectations were met and whether nurses perceived that there were any barriers to undertaking the education. Both quantitative and qualitative data were obtained by means of a questionnaire; all registered nurses in the hospital were invited to participate. The study indicates a high level of compliance with mandatory transfusion education and suggests both satisfaction and perceived benefits with transfusion education among those who responded. Some barriers were highlighted, but it was noted that these were not exclusive to transfusion education and in the current challenging environment with conflicting priorities on time, resolution may be complex. PMID:23634461

  4. Genes involved in centrosome-independent mitotic spindle assembly in Drosophila S2 cells.

    Science.gov (United States)

    Moutinho-Pereira, Sara; Stuurman, Nico; Afonso, Olga; Hornsveld, Marten; Aguiar, Paulo; Goshima, Gohta; Vale, Ronald D; Maiato, Helder

    2013-12-01

    Animal mitotic spindle assembly relies on centrosome-dependent and centrosome-independent mechanisms, but their relative contributions remain unknown. Here, we investigated the molecular basis of the centrosome-independent spindle assembly pathway by performing a whole-genome RNAi screen in Drosophila S2 cells lacking functional centrosomes. This screen identified 197 genes involved in acentrosomal spindle assembly, eight of which had no previously described mitotic phenotypes and produced defective and/or short spindles. All 197 genes also produced RNAi phenotypes when centrosomes were present, indicating that none were entirely selective for the acentrosomal pathway. However, a subset of genes produced a selective defect in pole focusing when centrosomes were absent, suggesting that centrosomes compensate for this shape defect. Another subset of genes was specifically associated with the formation of multipolar spindles only when centrosomes were present. We further show that the chromosomal passenger complex orchestrates multiple centrosome-independent processes required for mitotic spindle assembly/maintenance. On the other hand, despite the formation of a chromosome-enriched RanGTP gradient, S2 cells depleted of RCC1, the guanine-nucleotide exchange factor for Ran on chromosomes, established functional bipolar spindles. Finally, we show that cells without functional centrosomes have a delay in chromosome congression and anaphase onset, which can be explained by the lack of polar ejection forces. Overall, these findings establish the constitutive nature of a centrosome-independent spindle assembly program and how this program is adapted to the presence/absence of centrosomes in animal somatic cells.

  5. Blood transfusion in cardiac surgery: Does the choice of anesthesia or type of surgery matter?

    Directory of Open Access Journals (Sweden)

    Nešković Vojislava

    2013-01-01

    Full Text Available Background/Aim. In spite of the evidence suggesting a significant morbidity associated with blood transfusions, the use of blood and blood products remain high in cardiac surgery. To successfully minimize the need for blood transfusion, a systematic approach is needed. The aim of this study was to investigate the influence of different anesthetic techniques, general vs combine epidural and general anesthesia, as well as different surgery strategies, on-pump vs off-pump, on postoperative bleeding complications and the need for blood transfusions during perioperative period. Methods. Eighty-two consecutive patients scheduled for coronary artery bypass surgery were randomized according to surgical and anesthetic techniques into 4 different groups: group 1 (patients operated on off-pump, under general anesthesia; group 2 (patients operated on off-pump, with combined general and high thoracic epidural anesthesia; group 3 (patients operated on using standard revascularization technique, with the use of extracorporeal circulation, under general anesthesia, and group 4 (patients operated on using standard revascularization technique, with the use of extracorporeal circulation, with combined general and high thoracic epidural anesthesia. Indications for transfusion were based on clinical judgment, but a restrictive policy was encouraged. Bleeding was considered significant if it required transfusion of blood or blood products, or reopening of the chest. The quantity of transfused blood or blood products was specifically noted. Results. None of the patients was transfused blood or blood products during the surgery, and as many as 70/81 (86.4% patients were not transfused at all during hospital stay. No difference in postoperative bleeding or blood transfusion was noted in relation to the type of surgery and anesthetic technique applied. If red blood cells were transfused, postoperative bleeding was the most influential parameter for making clinical

  6. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    Energy Technology Data Exchange (ETDEWEB)

    Horita, Nobukatsu [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Tsuchiya, Kiichiro, E-mail: kii.gast@tmd.ac.jp [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Hayashi, Ryohei [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Department of Gastroenterology and Metabolism, Hiroshima University (Japan); Fukushima, Keita; Hibiya, Shuji; Fukuda, Masayoshi; Kano, Yoshihito; Mizutani, Tomohiro; Nemoto, Yasuhiro; Yui, Shiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan); Okamoto, Ryuichi; Nakamura, Tetsuya [Department of Advanced Therapeutics for Gastrointestinal Diseases, Graduate School, Tokyo Medical and Dental University (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (Japan)

    2014-11-28

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus.

  7. Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

    International Nuclear Information System (INIS)

    Highlights: • Lentivirus mixed with Matrigel enables direct infection of intestinal organoids. • Our original approach allows the marking of a single stem cell in a crypt. • Time-lapse imaging shows the dynamics of a single stem cell. • Our lentivirus transgene system demonstrates plural long-lived stem cells in a crypt. - Abstract: Background and aims: The dynamics of intestinal stem cells are crucial for regulation of intestinal function and maintenance. Although crypt stem cells have been identified in the intestine by genetic marking methods, identification of plural crypt stem cells has not yet been achieved as they are visualised in the same colour. Methods: Intestinal organoids were transferred into Matrigel® mixed with lentivirus encoding mCherry. The dynamics of mCherry-positive cells was analysed using time-lapse imaging, and the localisation of mCherry-positive cells was analysed using 3D immunofluorescence. Results: We established an original method for the introduction of a transgene into an organoid generated from mouse small intestine that resulted in continuous fluorescence of the mCherry protein in a portion of organoid cells. Three-dimensional analysis using confocal microscopy showed a single mCherry-positive cell in an organoid crypt that had been cultured for >1 year, which suggested the presence of long-lived mCherry-positive and -negative stem cells in the same crypt. Moreover, a single mCherry-positive stem cell in a crypt gave rise to both crypt base columnar cells and transit amplifying cells. Each mCherry-positive and -negative cell contributed to the generation of organoids. Conclusions: The use of our original lentiviral transgene system to mark individual organoid crypt stem cells showed that long-lived plural crypt stem cells might independently serve as intestinal epithelial cells, resulting in the formation of a completely functional villus

  8. Reporter cell activity within hydrogel constructs quantified from oxygen-independent bioluminescence.

    Science.gov (United States)

    Lambrechts, Dennis; Roeffaers, Maarten; Kerckhofs, Greet; Hofkens, Johan; Van de Putte, Tom; Schrooten, Jan; Van Oosterwyck, Hans

    2014-09-01

    By providing a three-dimensional (3D) support to cells, hydrogels offer a more relevant in vivo tissue-like environment as compared to two-dimensional cell cultures. Hydrogels can be applied as screening platforms to investigate in 3D the role of biochemical and biophysical cues on cell behaviour using bioluminescent reporter cells. Gradients in oxygen concentration that result from the interplay between molecular transport and cell metabolism can however cause substantial variability in the observed bioluminescent reporter cell activity. To assess the influence of these oxygen gradients on the emitted bioluminescence for various hydrogel geometries, a combined experimental and modelling approach was implemented. We show that the applied model is able to predict oxygen gradient independent bioluminescent intensities which correlate better to the experimentally determined viable cell numbers, as compared to the experimentally measured bioluminescent intensities. By analysis of the bioluminescence reaction dynamics we obtained a quantitative description of cellular oxygen metabolism within the hydrogel, which was validated by direct measurements of oxygen concentration within the hydrogel. Bioluminescence peak intensities can therefore be used as a quantitative measurement of reporter cell activity within a hydrogel, but an unambiguous interpretation of these intensities requires a compensation for the influence of cell-induced oxygen gradients on the luciferase activity.

  9. Decreasing the critical value of hemoglobin required for physician notification reduces the rate of blood transfusions

    Directory of Open Access Journals (Sweden)

    Larson EA

    2016-06-01

    Full Text Available Eric A Larson,1 Paul A Thompson,1,2 Zachary K Anderson,3 Keith A Anderson,4 Roxana A Lupu,1 Vicki Tigner,5 Wendell W Hoffman6,7 1Department of Internal Medicine, 2Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, 3Department of Internal Medicine, Fairview Health Services, Edina, MN, 4Department of Laboratory Medicine, Sanford School of Medicine, University of South Dakota, 5Medical Staff Services, 6Department of Infectious Disease, Sanford Health, Sanford USD Medical Center, 7Department of Infectious Disease, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USAAbstract: Red blood cell transfusions have been cited as one of the most overused therapeutic interventions in the USA. Excessively aggressive transfusion practices may be driven by mandatory physician notification of critical hemoglobin values that do not generally require transfusion. We examined the effect of decreasing the critical value of hemoglobin from 8 to 7 g/dL at our institution. Along with this change, mandatory provider notification for readings between 7 and 8 g/dL was rescinded. Transfusion rates were compared retrospectively during paired 5-month periods for patients presenting in three key hemoglobin ranges (6.00–6.99, 7.00–7.99, and 8.00–8.99 g/dL. A change in transfusion practices was hypothesized in the 7–8 g/dL range, which was no longer labeled critical and for which mandated physician calls were rescinded. Transfusion rates showed a statistically significant 8% decrease (P≤0.0001 during the 5-month period post change in our transfusion practices. This decrease in the 7.00–7.99 g/dL range was significantly greater than the 2% decrease observed in either the 6–6.99 g/dL (P=0.0017 or 8–8.99 g/dL (P≤0.0001 range. Cost savings of up to $700,000/year were extrapolated from our results showing 491 fewer units of red blood cells transfused during the 5-month post change. These cost

  10. Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation and Anchorage-Independence in MDCK Cells

    OpenAIRE

    Chia Chu; Donald P Bottaro; Betenbaugh, Michael J.; Joseph Shiloach

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage-dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5). The comparison identified several genes involved in the EMT ...

  11. LIF independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease

    OpenAIRE

    Griffiths, Dean S.; Li, Juan; Dawson, Mark A.; Trotter, Matthew W B; Cheng, Yi-Han; Smith, Aileen M.; Mansfield, William; Liu, Pentao; Kouzarides, Tony; Nichols, Jennifer; Bannister, Andrew J; Green, Anthony R.; Göttgens, Berthold

    2010-01-01

    Activating mutations in the tyrosine kinase JAK2 cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. LIF signalling through JAK-STAT enables ES cell self-renewal. Here we show that mouse ES cells carrying the human JAK2V617F mutation could self-renew in chemically defined conditions without cytokines or small molecule inhibitors independently of JAK signalling through STAT3 or PI3K pathways. Phosphorylation of histone H3Y41 by J...

  12. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells.

    NARCIS (Netherlands)

    Broker, L.E.; Huisman, C.; Span, SW; Rodriguez, J.A.; Kruyt, F.A.E.; Giaccone, G.

    2004-01-01

    We have previously reported that the microtubule stabilizing agents (MSAs) paclitaxel, epothilone B and discodermolide induce caspase-independent cell death in non-small cell lung cancer (NSCLC) cells. Here we present two lines of evidence indicating a central role for the lysosomal protease catheps

  13. [Blood transfusion and supply chain management safety].

    Science.gov (United States)

    Quaranta, Jean-François; Caldani, Cyril; Cabaud, Jean-Jacques; Chavarin, Patricia; Rochette-Eribon, Sandrine

    2015-02-01

    The level of safety attained in blood transfusion now makes this a discipline better managed care activities. This was achieved both by scientific advances and policy decisions regulating and supervising the activity, as well as by the quality system, which we recall that affects the entire organizational structure, responsibilities, procedures, processes and resources in place to achieve quality management. So, an effective quality system provides a framework within which activities are established, performed in a quality-focused way and continuously monitored to improve outcomes. This system quality has to irrigate all the actors of the transfusion, just as much the establishments of blood transfusion than the health establishments.

  14. [Blood transfusion and supply chain management safety].

    Science.gov (United States)

    Quaranta, Jean-François; Caldani, Cyril; Cabaud, Jean-Jacques; Chavarin, Patricia; Rochette-Eribon, Sandrine

    2015-02-01

    The level of safety attained in blood transfusion now makes this a discipline better managed care activities. This was achieved both by scientific advances and policy decisions regulating and supervising the activity, as well as by the quality system, which we recall that affects the entire organizational structure, responsibilities, procedures, processes and resources in place to achieve quality management. So, an effective quality system provides a framework within which activities are established, performed in a quality-focused way and continuously monitored to improve outcomes. This system quality has to irrigate all the actors of the transfusion, just as much the establishments of blood transfusion than the health establishments. PMID:25578550

  15. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  16. Alcohol-positive multiple trauma patients with and without blood transfusion: an outcome analysis

    Directory of Open Access Journals (Sweden)

    Stuttmann Ralph

    2009-03-01

    Full Text Available Abstract Background Blood transfusion is a common therapy for multiple trauma patients, and is often performed soon after hospital admission. It is unclear whether the need for a blood transfusion in multiply injured patients presenting with a positive blood alcohol concentration (BAC is associated with increased morbidity/mortality, since their risk behavior differs significantly from patients with a negative BAC. In this study, we evaluated the role of blood transfusion in the treatment of BAC-positive multiple trauma patients. Patients In a three-year period, 164 patients at a single trauma center presented with a positive BAC, and 145 met the inclusion criteria for further evaluation and regression analysis. We compared patients who were transfused (n = 76 with those who were not transfused (n = 69. Results In both groups, the most common causes of trauma were traffic accidents and falls. Most patients were admitted to the hospital from the scene of the accident (77.2% and were male (89.0%. Transfused patients had a lower GCS (p ≤ .001 and her ISS (p ≤ .001, were more likely to have severe head injuries (p ≤ .001, tended to have higher BACs (p = .053, had lower hemoglobin levels and prothrombin times in the first 24 hours (p ≤ .001, had lower lactate levels, had higher rates of intubation (p ≤ .001 and ICU admission, and had longer ICU stays and artificial ventilation times (p ≤ .001. Mortality was significantly higher in transfused patients (n = 15 vs. n = 3, p ≤ .001. Non-survivors were more likely to have severe head injuries; be intubated and ventilated; be older; have higher ISS scores, lactate levels, and numbers of transfusions in the first 24 hours; and have lower GCS scores, hemoglobin measurements, and prothrombin levels. In a binary logistic regression model, only age (p = .009 and ISS (p = .004 independently predicted mortality. Conclusion In our single-center study, the BAC of multiple trauma patients and the

  17. Transfusion-related necrotizing enterocolitis: a conceptual framework.

    Science.gov (United States)

    Marin, Terri; Strickland, Ora L

    2013-06-01

    Necrotizing enterocolitis (NEC) is a disease primarily of prematurity characterized by partial or entire gut necrosis and is associated with significant mortality and morbidity. Recent studies report that approximately 25% to 35% of very low-birth-weight infants less than 1500 g receiving packed red blood cell transfusions develop temporally associated NEC, known as transfusion-related NEC (TR-NEC). Although there are many known risk factors for NEC, this article focuses on 3 contributing factors: packed red blood cell transfusions, enteral feedings, and gastrointestinal immaturity. Previous data suggest that these factors may interact to affect neonatal intestinal tissue oxygenation, which may lead to tissue ischemia, resulting in intestinal injury. This article presents a conceptual framework that combines current theoretical perspectives for TR-NEC, and reviews previous research examining related variables and how their interaction may increase the risk for TR-NEC development. In addition, incorporation of the proposed framework to guide future research and nursing care in this area is discussed.

  18. Improving platelet transfusion safety: biomedical and technical considerations.

    Science.gov (United States)

    Garraud, Olivier; Cognasse, Fabrice; Tissot, Jean-Daniel; Chavarin, Patricia; Laperche, Syria; Morel, Pascal; Lefrère, Jean-Jacques; Pozzetto, Bruno; Lozano, Miguel; Blumberg, Neil; Osselaer, Jean-Claude

    2016-03-01

    Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. PMID:26674828

  19. Jak2-Independent Activation of Stat3 by Intracellular Angiotensin II in Human Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Rekha Singh

    2011-01-01

    Full Text Available Ang II is shown to mediate the stimulatory effect of high glucose on TGF-b1 and extracellular matrix proteins in glomerular mesangial cells. Also inhibition of Ang II formation in cell media (extracellular and lysates (intracellular blocks high-glucose effects on TGF-b1 and matrix more effectively compared to inhibition of extracellular Ang II alone. To investigate whether intracellular Ang II can stimulate TGF-b1 and matrix independent of extracellular Ang II, cultured human mesangial cells were transfected with Ang II to increase intracellular Ang II levels and its effects on TGF-b1 and matrix proteins were determined. Prior to transfection, cells were treated with candesartan to block extracellular Ang II-induced responses via cell membrane AT1 receptors. Transfection of cells with Ang II resulted in increased levels of intracellular Ang II which was accompanied by increased production of TGF-b1, collagen IV, fibronectin, and cell proliferation as well. On further examination, intracellular Ang II was found to activate Stat3 transcription factor including increased Stat3 protein expression, tyrosine 705 phosphorylation, and DNA-binding activity. Treatment with AG-490, an inhibitor of Jak2, did not block intracellular Ang II-induced Stat3 phosphorylation at tyrosine 705 residue indicating a Jak2-independent mechanism used by intracellular Ang II for Stat3 phosphorylation. In contrast, extracellular Ang II-induced tyrosine 705 phosphorylation of Stat3 was inhibited by AG-490 confirming the presence of a Jak2-dependent pathway. These findings suggest that intracellular Ang II increases TGF-b1 and matrix in human mesangial cells and also activates Stat3 transcription factor without involvement of the extracellular Ang II signaling pathway.

  20. Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xuesong Liu

    2001-01-01

    Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

  1. 31P MAS-NMR of human erythrocytes: independence of cell volume from angular velocity.

    Science.gov (United States)

    Kuchel, P W; Bubb, W A; Ramadan, S; Chapman, B E; Philp, D J; Coen, M; Gready, J E; Harvey, P J; McLean, A J; Hook, J

    2004-09-01

    31P magic angle spinning NMR (MAS-NMR) spectra were obtained from suspensions of human red blood cells (RBCs) that contained the cell-volume-sensitive probe molecule, dimethyl methylphosphonate (DMMP). A mathematical representation of the spectral-peak shape, including the separation and width-at-half-height in the 31P NMR spectra, as a function of rotor speed, enabled us to explore the extent to which a change in cell volume would be reflected in the spectra if it occurred. We concluded that a fractional volume change in excess of 3% would have been detected by our experiments. Thus, the experiments indicated that the mean cell volume did not change by this amount even at the highest spinning rate of 7 kHz. The mean cell volume and intracellular 31P line-width were independent of the packing density of the cells and of the initial cell volume. The relationship of these conclusions to other non-NMR studies of pressure effects on cells is noted. PMID:15334588

  2. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell

    Institute of Scientific and Technical Information of China (English)

    WU Zhi-qun; ZHANG Rui; Connie Chao; ZHANG Ji-feng; ZHANG Yuan-qiang

    2007-01-01

    Background Histone deacetylase inhibitors (HDACIs) have been reported to induce apoptosis in cancer cells.The effects of trichostatin A (TSA) on gastric cancer cells have not been well characterized.This study was aimed to explore the effects and mechanisms of TSA on human gastric cancer SGC-7901 cells.Methods The cells were treated with TSA and analyzed by cell proliferation assay,Western blot,TUNEL assay,flow cytometry by fluorescein isothiocyanate (FITC) conjugated with Annexin V and PI staining,immunofluorescence analysis,analysis of subcellular fractionation,gene chips and real time polymerase chain reaction (PCR).Results TSA could inhibit cell growth and induced apoptosis in gastric cancer SGC-7901 cells through the regulation of apoptosis-related genes,such as Bcl-2,Bax and survivin.Further study indicated that the pan-caspase inhibitor z-VAD-fmk did not inhibit the apoptosis induced by TSA,and we did not observe the cleavage of poly ADP ribose polymerase(PARP)after TSA treatment too.In addition,apoptosis inducing factor (AIF) and EndoG were found to translocate from mitochondria to nucleus in the immunofluorescence assay and the Western analysis of subcellular fractionation confirmed the result of immunofluorescence assay.Conclusions The apoptosis induced by TSA in gastric cancer SGC-7901 cells involves a caspase-independent pathway.

  3. Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells.

    Science.gov (United States)

    Koldehoff, Michael; Zakrzewski, Johannes L; Klein-Hitpass, Ludger; Beelen, Dietrich W; Elmaagacli, Ahmet H

    2008-01-01

    To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, the naturally Gfi-1B overexpressing cell line K562 was cultured in the presence of Gfi-1B target-specific small interfering RNA (siRNA). SiRNA treatment significantly knocked down Gfi-1B expression with an efficiency of nearly 90%. Analysis of the siRNA silencing protocol by colony-forming units ensured that it was not cytotoxic. Samples from Gfi-1B overexpressing cells and cells with knocked-down Gfi-1B were analyzed by oligonucleotide microarray technology and based upon rigorous statistical analysis of the data; relevant genes were chosen for confirmation by reserve transcriptase-polymerase chain reaction, including MYC/MYCBP and CDKN1A. Interestingly, transcripts within components of the signalling cascade of immune cells (PLD1, LAMP1, HSP90, IL6ST), of the tyrosine kinase pathway (TPR, RAC3) and of the transcription factors (RAC3, CEP290, JEM-1, ATR, MYC, SMC3, RARA, RBBP6) were found to be differentially expressed in Gfi-1B overexpressing cells compared to controls. Individual genes such as ZDHHC17, DMXL1, ZNF292 were found to be upregulated in Gfi-1B overexpressing cells. In addition, down-regulated transcripts showed cell signaling transcripts for several chemokine gene members including GNAL, CXCL5, GNL3L, GPR65, TMEM30, BCL11B and transcription factors (GTF2H3, ATXN3). In conclusion, several essential cell signalling factors, as well as transcriptional and post-translational regulation genes were differentially expressed in cells that overexpressed Gfi-1B compared to control cells with knocked-down Gfi-1B. Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations. PMID:18224412

  4. Blood transfusion in the para-Bombay phenotype.

    Science.gov (United States)

    Lin-Chu, M; Broadberry, R E

    1990-08-01

    The H-deficient phenotypes found in Chinese so far, have all been secretors of soluble blood group substances in saliva. The corresponding isoagglutinin activity (e.g. anti-B in OB(Hm) persons) has been found to be weak in all cases. To determine the clinical significance of these weak isoagglutinins 51Cr red cell survival tests were performed on three OB(Hm) individuals transfused with small volumes (4 ml) of groups B and O RBC. Rapid destruction of most of the RBC occurred whether or not the isoagglutinins of the OB(Hm) individuals were indirect antiglobulin test (IAGT) reactive. When a larger volume (54 ml packed RBC) of group B cells (weakly incompatible by IAGT) was transfused to another OB(Hm) individual with IAGT active anti-HI, the survival of the transfused RBC was 93% at 24 h, with 30% of the RBC remaining in the circulation at 28 d in contrast to 76% as would be expected if the survival was normal. Therefore when whole units of blood of normal ABO blood groups, compatible by IAGT, are transfused, the survival is expected to be almost normal. These weak isoagglutinins may not be very clinically significant and we suggest that when para-Bombay blood is not available, the compatibility testing for OA(Hm) persons should be performed with group A and group O packed RBC; OB(Hm) with group B and group O packed RBC: OAB(Hm) with groups A, B, AB and O packed RBC. For cross matching, the indirect antiglobulin test by a prewarmed technique should be used.

  5. The impact of blood transfusion on perioperative outcomes following gastric cancer resection: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database

    Science.gov (United States)

    Elmi, Maryam; Mahar, Alyson; Kagedan, Daniel; Law, Calvin H.L.; Karanicolas, Paul J.; Lin, Yulia; Callum, Jeannie; Coburn, Natalie G.; Hallet, Julie

    2016-01-01

    Background Red blood cell transfusions (RBCT) carry risk of transfusion-related immunodulation that may impact postoperative recovery. This study examined the association between perioperative RBCT and short-term postoperative outcomes following gastrectomy for gastric cancer. Methods Using the American College of Surgeons National Surgical Quality Improvement Program database, we compared outcomes of patients (transfused v. nontransfused) undergoing elective gastrectomy for gastric cancer (2007–2012). Outcomes were 30-day major morbidity, mortality and length of stay. The association between perioperative RBCT and outcomes was estimated using modified Poisson, logistic, or negative binomial regression. Results Of the 3243 patients in the entire cohort, we included 2884 patients with nonmissing data, of whom 535 (18.6%) received RBCT. Overall 30-day major morbidity and mortality were 20% and 3.5%, respectively. After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased 30-day mortality (relative risk [RR] 3.1, 95% confidence interval [CI] 1.9–5.0), major morbidity (RR 1.4, 95% CI 1.2–1.8), length of stay (RR 1.2, 95% CI 1.1–1.2), infections (RR 1.4, 95% CI 1.1–1.6), cardiac complications (RR 1.8, 95% CI 1.0–3.2) and respiratory failure (RR 2.3, 95% CI 1.6–3.3). Conclusion Red blood cell transfusions are associated with worse postoperative short-term outcomes in patients with gastric cancer. Blood management strategies are needed to reduce the use of RBCT after gastrectomy for gastric cancer. PMID:27668330

  6. Increased Th22 cells are independently associated with Th17 cells in type 1 diabetes.

    Science.gov (United States)

    Xu, Xinyu; Zheng, Shuai; Yang, Fan; Shi, Yun; Gu, Yong; Chen, Heng; Zhang, Mei; Yang, Tao

    2014-05-01

    Type 1 diabetes (T1D) is perceived as an autoimmune disease caused by T cell-mediated destruction of the insulin-producing pancreatic β cells. However, the number of inflammatory T cells in blood, as well as the relative importance of each cell type is unclear. Forty-two patients with T1D and 30 controls were enrolled. Circulating primary CD4(+) or CD8(+) T cells were quantified with 5-color flow cytometry. Serum IL-22 and IL-17 levels were examined by ELISA. Serum autoantibodies were measured by radio-binding assays, using (35)S-labeled glutamic acid decarboxylase-65 (GAD65), protein tyrosine phosphatase-2 (IA-2), and zinc transporter 8 (ZnT8). Th17-Th22 and Tc1-Tc17 were significantly elevated in patients with T1D compared to control subjects, while there were no significant differences in Th1 cells. The levels of these T cells in different stages of T1D were investigated. Th22 cells showed a positive correlation with Th17 cells in T1D patients. However, we did not find any correlation between IL-17 and IL-22 in sera. Autoantibodies were not significantly different between patients with early T1D and those who have had it for a longer duration. This study indicates that Th22 may contribute to the pathogenesis of T1D. Blockade of Th22 cells might be of clinical profit in T1D patients. PMID:23928796

  7. Influence of antiplatelet-anticoagulant drugs on the need of blood components transfusion after vesical transurethral resection

    Directory of Open Access Journals (Sweden)

    Alvaro Julio Virseda-Rodríguez

    2015-07-01

    Full Text Available Aims: The effect of the antithrombotic preventive therapy on haemorrhage keeps uncertain. We investigate the influence of the antiplatelet and anticoagulant drugs (AP/AC drugs on the transfusion requirement after vesical transurethral resection (VTUR. We also describe the epidemiology of the blood components transfusion in our department. Materials and Methods: Retrospective observational study of a series of patients needing blood transfusion at the Urology Department between June 2010 and June 2013. Selection of 100 consecutive patients who were transfused after VTUR due to bladder transitional cell carcinoma (BTCC (group A = GA. Control group: 100 consecutive patients who underwent VTUR due to BTCC and were not transfused (group B = GB. Transfusion criteria: Haemoglobin < 8 g/dl + anaemia symptoms. Age, gender, associated AP/AC treatment, secondary diagnoses, toxics, tumour stage and grade were analysed. Results: 212 patients required transfusion of a blood component. 169 were men (79% and 43 women (21%. Median age 77.59 years (SD 9.42, range 50-92. Secondary diagnoses: Diabetes Mellitus 64%, high blood pressure 77%, dyslipidemia 52%. 60% of patients were previously treated with AP/AC drugs. Average Haemoglobin pre-transfusion values: 7.4 g/dl (DE ± 0.7. Average Haemoglobin post-transfusion values: 8.9 g/Dl (DE ± 0.72. Most frequent transfusion indications were bladder cancer (37%, kidney cancer (11%, prostate cancer (8%, benign prostatic hyperplasia (BHP (8%, other urological diagnoses (36%. Intraoperative transfusions indicated by the anaesthesiologist: kidney cancer (33%, BPH (28%. Patients who underwent VTUR due to BTCC were older in GA (77.59 years SD 9.42 than in GB (68.98 years SD 11.78 (p = 0.0001. Similar gender distribution (15 women in GA and 24 in GB. Less patients were asked to keep their treatment with ASA 100mg (AcetylSalicylicAcid in GA (25.64% than in GB (50% (p = 0.0330. More aggressive tumour grade in GA (p = 0.0003 and

  8. Early, Prehospital Activation of the Walking Blood Bank Based on Mechanism of Injury Improves Time to Fresh Whole Blood Transfusion.

    Science.gov (United States)

    Bassett, Aaron K; Auten, Jonathan D; Zieber, Tara J; Lunceford, Nicole L

    2016-01-01

    Balanced component therapy (BCT) remains the mainstay in trauma resuscitation of the critically battle injured. In austere medical environments, access to packed red blood cells, apheresis platelets, and fresh frozen plasma is often limited. Transfusion of warm, fresh whole blood (FWB) has been used to augment limited access to full BCT in these settings. The main limitation of FWB is that it is not readily available for transfusion on casualty arrival. This small case series evaluates the impact early, mechanism-of-injury (MOI)-based, preactivation of the walking blood bank has on time to transfusion. We report an average time of 18 minutes to FWB transfusion from patient arrival. Early activation of the walking blood bank based on prehospital MOI may further reduce the time to FWB transfusion.

  9. Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Sen-XiangYan; YasuoEjima; RyoheiSasaki; Shu-SenZheng; YusukeDemizu; ToshinoriSoejima; KazuroSugimura

    2004-01-01

    Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DUI45 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment.Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU 145 cells. Twenty four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein,especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DUI45 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B 1 and less dramatically cdc-2, but stably elevated p21cip1 levels with increasing genistein concentrations.Conclusion: Genistein enhanced the radiosensitivity of DUI45 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair. (Asian J Androl 2004 Dec; 6: 285-290)

  10. Blood transfusion practices in obstetric anaesthesia

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2014-01-01

    Full Text Available Blood transfusion is an essential component of emergency obstetric care and appropriate blood transfusion significantly reduces maternal mortality. Obstetric haemorrhage, especially postpartum haemorrhage, remains one of the major causes of massive haemorrhage and a prime cause of maternal mortality. Blood loss and assessment of its correct requirement are difficult in pregnancy due to physiological changes and comorbid conditions. Many guidelines have been used to assess the requirement and transfusion of blood and its components. Infrastructural, economic, social and religious constraints in blood banking and donation are key issues to formulate practice guidelines. Available current guidelines for transfusion are mostly from the developed world; however, they can be used by developing countries keeping available resources in perspective.

  11. Liver disease in transfusion dependent thalassaemia major

    OpenAIRE

    C. Li; Chik, K; Lam, C.; To, K; Yu, S.; Lee, V.; Shing, M.; Cheung, A; Yuen, P

    2002-01-01

    Aims: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers.

  12. Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation.

    Science.gov (United States)

    Jia, Ting; Anandhan, Annandurai; Massilamany, Chandirasegaran; Rajasekaran, Rajkumar A; Franco, Rodrigo; Reddy, Jay

    2015-12-01

    Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139-151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not selective, because both proliferating and non-proliferating cells were equally affected independent of antigenic stimulation. Furthermore, DHT-exposed PLP 139-151-specific T cells did not show any shift in cytokine production; rather, frequencies of cytokine-producing PLP-specific T cells were significantly reduced, irrespective of T helper (Th) 1, Th2, and Th17 subsets of cytokines. By evaluating cell death and autophagy pathways, we provide evidence for the induction of autophagy to be associated with cell death caused by DHT. Taken together, the data provide new insights into the role of DHT and indicate that cell death and autophagy contribute to the therapeutic effects of androgens in autoreactive T cells.

  13. Platelet Transfusion – The New Immunology of an Old Therapy

    OpenAIRE

    Stolla, Moritz; Refaai, Majed A.; Heal, Joanna M.; Spinelli, Sherry L.; Garraud, Olivier; Phipps, Richard P.; Blumberg, Neil

    2015-01-01

    Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged ...

  14. A Cilia Independent Role of Ift88/Polaris during Cell Migration.

    Directory of Open Access Journals (Sweden)

    Christopher Boehlke

    Full Text Available Ift88 is a central component of the intraflagellar transport (Ift complex B, essential for the building of cilia and flagella from single cell organisms to mammals. Loss of Ift88 results in the absence of cilia and causes left-right asymmetry defects, disordered Hedgehog signaling, and polycystic kidney disease, all of which are explained by aberrant ciliary function. In addition, a number of extraciliary functions of Ift88 have been described that affect the cell-cycle, mitosis, and targeting of the T-cell receptor to the immunological synapse. Similarly, another essential ciliary molecule, the kinesin-2 subunit Kif3a, which transports Ift-B in the cilium, affects microtubule (MT dynamics at the leading edge of migrating cells independently of cilia. We now show that loss of Ift88 impairs cell migration irrespective of cilia. Ift88 is required for the polarization of migrating MDCK cells, and Ift88 depleted cells have fewer MTs at the leading edge. Neither MT dynamics nor MT nucleation are dependent on Ift88. Our findings dissociate the function of Ift88 from Kif3a outside the cilium and suggest a novel extraciliary function for Ift88. Future studies need to address what unifying mechanism underlies the different extraciliary functions of Ift88.

  15. A Cilia Independent Role of Ift88/Polaris during Cell Migration.

    Science.gov (United States)

    Boehlke, Christopher; Janusch, Heike; Hamann, Christoph; Powelske, Christian; Mergen, Miriam; Herbst, Henriette; Kotsis, Fruzsina; Nitschke, Roland; Kuehn, E Wolfgang

    2015-01-01

    Ift88 is a central component of the intraflagellar transport (Ift) complex B, essential for the building of cilia and flagella from single cell organisms to mammals. Loss of Ift88 results in the absence of cilia and causes left-right asymmetry defects, disordered Hedgehog signaling, and polycystic kidney disease, all of which are explained by aberrant ciliary function. In addition, a number of extraciliary functions of Ift88 have been described that affect the cell-cycle, mitosis, and targeting of the T-cell receptor to the immunological synapse. Similarly, another essential ciliary molecule, the kinesin-2 subunit Kif3a, which transports Ift-B in the cilium, affects microtubule (MT) dynamics at the leading edge of migrating cells independently of cilia. We now show that loss of Ift88 impairs cell migration irrespective of cilia. Ift88 is required for the polarization of migrating MDCK cells, and Ift88 depleted cells have fewer MTs at the leading edge. Neither MT dynamics nor MT nucleation are dependent on Ift88. Our findings dissociate the function of Ift88 from Kif3a outside the cilium and suggest a novel extraciliary function for Ift88. Future studies need to address what unifying mechanism underlies the different extraciliary functions of Ift88. PMID:26465598

  16. NOPO modulates Egr-induced JNK-independent cell death in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Xianjue Ma; Jiuhong Huang; Lixia Yang; Yang Yang; Wenzhe Li; Lei Xue

    2012-01-01

    Tumor necrosis factor (TNF) family ligands play essential roles in regulating a variety of cellular processes including proliferation,differentiation and survival.Expression of Drosophila TNF ortholog Eiger (Egr) induces JNK-dependent cell death,while the roles of caspases in this process remain elusive.To further delineate the Egr-triggered cell death pathway,we performed a genetic screen to identify dominant modifiers of the Egr-induced cell death phenotype.Here we report that Egr elicits a caspase-mediated cell death pathway independent of JNK signaling.Furthermore,we show NOPO,the Drosophila ortholog of TRIP (TRAF interacting protein) encoding an E3 ubiquitin ligase,modulates Egr-induced Caspase-mediated cell death through transcriptional activation of pro-apoptotic genes reaper and hid.Finally,we found Bendless and dUEV1a,an ubiquitin-conjugating E2 enzyme complex,regulates NOPO-triggered cell death.Our results indicate that the Ben-dUEV1a complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively.

  17. Recombinant human erythropoietin and blood transfusion in low-birth weight preterm infants under restrictive transfusion guidelines

    International Nuclear Information System (INIS)

    To compare the number and volume of red blood cell transfusions (RBCTs) in very low birth weight infants under restrictive red blood cell transfusion guidelines with and without erythropoietin administration. In a controlled clinical trial conducted at the neonatal intensive care unit of Alzahra Hospital, Isfahan, Iran, between April 2002 to April 2004, 60 premature infants with gestational age up to 34 weeks, birth weight up to 1500 g, and postnatal age between 8 and 14 days were included. The newborns were randomized into 2 groups: Group 1 received 3 doses of 400 IU/kg erythropoietin per week for 6 weeks, and Group 2 received no treatment aside from their conventional medications. The 2 groups did not differ significantly with respect to their mean gestational age, birth weight and hematocrit at the study entry. Fewer transfusions were administered to those receiving erythropoietin (26.7% versus 50%, p=0.03), but there was no statistically significant difference between groups with respect to volume of transfusion. Compared with the placebo group, the infants receiving erythropoietin had a higher mean hematocrit (34% +/- 4.3 versus 29% +/- 5.9, p<0.001) and absolute reticulocyte count (57 +/- 19 versus 10 +/- 4.8 x 106, p<0.001) at the end of the study. We found no significant difference in the incidence of thrombocytopenia and leukopenia between the 2 groups. We conclude that when the restrictive RBCT guidelines were followed, treatment with erythropoietin can be useful in reduction of the number of RBCTs. (author)

  18. Transfusion support in patients with dengue fever

    OpenAIRE

    Kaur, Paramjit; Kaur, Gagandeep

    2014-01-01

    Dengue fever has emerged as a global public health problem in the recent decades. The clinical spectrum of the disease ranges from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. The disease is characterized by increased capillary permeability, thrombocytopenia and coagulopathy. Thrombocytopenia with hemorrhagic manifestations warrants platelet transfusions. There is lack of evidence-based guidelines for transfusion support in patients with dengue fever. This contributes t...

  19. Transcription-independent function of Polycomb group protein PSC in cell cycle control.

    Science.gov (United States)

    Mohd-Sarip, Adone; Lagarou, Anna; Doyen, Cecile M; van der Knaap, Jan A; Aslan, Ülkü; Bezstarosti, Karel; Yassin, Yasmin; Brock, Hugh W; Demmers, Jeroen A A; Verrijzer, C Peter

    2012-05-11

    Polycomb group (PcG) proteins control development and cell proliferation through chromatin-mediated transcriptional repression. We describe a transcription-independent function for PcG protein Posterior sex combs (PSC) in regulating the destruction of cyclin B (CYC-B). A substantial portion of PSC was found outside canonical PcG complexes, instead associated with CYC-B and the anaphase-promoting complex (APC). Cell-based experiments and reconstituted reactions established that PSC and Lemming (LMG, also called APC11) associate and ubiquitylate CYC-B cooperatively, marking it for proteosomal degradation. Thus, PSC appears to mediate both developmental gene silencing and posttranslational control of mitosis. Direct regulation of cell cycle progression might be a crucial part of the PcG system's function in development and cancer.

  20. Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.

    Directory of Open Access Journals (Sweden)

    Alexander M Many

    Full Text Available The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.

  1. DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells.

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    Myrna Candelaria

    Full Text Available BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase.

  2. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

  3. [Correlation of hemogram changes during pregnancy of healthy women with postpartum blood transfusion].

    Science.gov (United States)

    Li, Hui; Chen, Lin-Feng; Wang, Shu-Ying; Wang, Yan; Shi, Hong-Mei; Wang, De-Qing

    2012-10-01

    This study was aimed to explore the correlation of hemogram changes during pregnancy of healthy women with postpartum blood transfusion. The outpatient and inpatient information of expectant lying-in women in our hospitals was collected, the route blood test, lever and kidney function and blood coagulation function tests were performed from the 4th to the 10th month of pregnancy. The pregnant women without underlying diseases and non-elderly pregnant women with single fetus were selected as the subjects of study. They were divided into postpartum blood transfusion group and non-blood transfusion group. The white blood cell (WBC) count, hemoglobin (Hb) level, platelet (Plt) count, plateletocrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW) were compared in 2 groups. The results showed that 68 cases out of 450 expectant lying-in women received blood transfusion, among them 30 cases with complete data of puerperal transfusion were taken as blood transfusion group, the 28 cases of non transfusion puerperal as control group. There was no significant difference of hemogram changes between the two groups. However, there was a slight decline in Plt count and Hb level of late pregnant women. What is more, there was no correlation between Plt count change and the PCT, MPV and PDW. It is concluded that the changes of hemogram during pregnancy has no correlation with postpartum hemorrhage and blood transfusion in healthy pregnant women, the Plt count and Hb level of pregnant women slightly decline. Nevertheless, PCT, MPV and PDW are within the normal range.

  4. Factors related to transfusion in very low birthweight infants treated with erythropoietin.

    Science.gov (United States)

    Maier, R. F.; Obladen, M.; Messinger, D.; Wardrop, C. A.

    1996-01-01

    The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO 'non-responders', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants. PMID:8777681

  5. Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

    International Nuclear Information System (INIS)

    -dependent manner. We conclude that airway epithelial cells are sensitive to both CB2R-dependent and independent effects mediated by THC

  6. MTOR-independent induction of autophagy in trabecular meshwork cells subjected to biaxial stretch.

    Science.gov (United States)

    Porter, Kristine M; Jeyabalan, Nallathambi; Liton, Paloma B

    2014-06-01

    The trabecular meshwork (TM) is part of a complex tissue that controls the exit of aqueous humor from the anterior chamber of the eye, and therefore helps maintaining intraocular pressure (IOP). Because of variations in IOP with changing pressure gradients and fluid movement, the TM and its contained cells undergo morphological deformations, resulting in distention and stretching. It is therefore essential for TM cells to continuously detect and respond to these mechanical forces and adapt their physiology to maintain proper cellular function and protect against mechanical injury. Here we demonstrate the activation of autophagy, a pro-survival pathway responsible for the degradation of long-lived proteins and organelles, in TM cells when subjected to biaxial static stretch (20% elongation), as well as in high-pressure perfused eyes (30mmHg). Morphological and biochemical markers for autophagy found in the stretched cells include elevated LC3-II levels, increased autophagic flux, and the presence of autophagic figures in electron micrographs. Furthermore, our results indicate that the stretch-induced autophagy in TM cells occurs in an MTOR- and BAG3-independent manner. We hypothesize that activation of autophagy is part of the physiological response that allows TM cells to cope and adapt to mechanical forces. PMID:24583119

  7. Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells.

    Science.gov (United States)

    Karabay, Arzu Zeynep; Koc, Asli; Ozkan, Tulin; Hekmatshoar, Yalda; Sunguroglu, Asuman; Aktan, Fugen; Buyukbingol, Zeliha

    2016-01-01

    Methylsulfonylmethane (MSM) is an organic sulfur-containing compound which has been used as a dietary supplement for osteoarthritis. MSM has been shown to reduce oxidative stress and inflammation, as well as exhibit apoptotic or anti-apoptotic effects depending on the cell type or activating stimuli. However, there are still a lot of unknowns about the mechanisms of actions of MSM. In this study, MSM was tested on colon cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis revealed that MSM inhibited cell viability and increased apoptotic markers in both HCT-116 p53 +/+ and HCT-116 p53 -/- colon cancer cells. Increased poly (ADP-ribose) polymerase (PARP) fragmentation and caspase-3 activity by MSM also supported these findings. MSM also modulated the expression of various apoptosis-related genes and proteins. Moreover, MSM was found to increase c-Jun N-terminal kinases (JNK) phosphorylation in both cell lines, dose-dependently. In conclusion, our results show for the first time that MSM induces apoptosis in HCT-116 colon cancer cells regardless of their p53 status. Since p53 is defective in >50% of tumors, the ability of MSM to induce apoptosis independently of p53 may offer an advantage in anti-tumor therapy. Moreover, the remarkable effect of MSM on Bim, an apoptotic protein, also suggests its potential use as a novel chemotherapeutic agent for Bim-targeted anti-cancer therapies. PMID:27428957

  8. Well being of obstetric patients on minimal blood transfusions (WOMB trial

    Directory of Open Access Journals (Sweden)

    Bloemenkamp Kitty WM

    2010-12-01

    Full Text Available Abstract Background Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands. Methods/Design The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D. Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be

  9. Effect of Blood Donor Characteristics on Transfusion Outcomes: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chassé, Michaël; McIntyre, Lauralyn; English, Shane W; Tinmouth, Alan; Knoll, Greg; Wolfe, Dianna; Wilson, Kumanan; Shehata, Nadine; Forster, Alan; van Walraven, Carl; Fergusson, Dean A

    2016-04-01

    Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk

  10. Long-Term follow up after intra-Uterine transfusionS; the LOTUS study

    Directory of Open Access Journals (Sweden)

    Kanhai Humphrey HH

    2010-12-01

    Full Text Available Abstract Background The Leiden University Medical Center (LUMC is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT. Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children. Methods/Design We set up a large long-term observational follow-up study (LOTUS study, in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion. The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR. All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI, a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development Discussion The LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The

  11. Riluzole mediates anti-tumor properties in breast cancer cells independent of metabotropic glutamate receptor-1.

    Science.gov (United States)

    Speyer, Cecilia L; Nassar, Mahdy A; Hachem, Ali H; Bukhsh, Miriam A; Jafry, Waris S; Khansa, Rafa M; Gorski, David H

    2016-06-01

    Riluzole, the only drug approved by the FDA for treating amyotrophic lateral sclerosis, inhibits melanoma proliferation through its inhibitory effect on glutamatergic signaling. We demonstrated that riluzole also inhibits the growth of triple-negative breast cancer (TNBC) and described a role for metabotropic glutamate receptor-1 (GRM1) in regulating TNBC cell growth and progression. However, the role of GRM1 in mediating riluzole's effects in breast cancer has not been fully elucidated. In this study, we seek to determine how much of riluzole's action in breast cancer is mediated through GRM1. We investigated anti-tumor properties of riluzole in TNBC and ER+ cells using cell growth, invasion, and soft-agar assays and compared riluzole activity with GRM1 levels. Using Lentiviral vectors expressing GRM1 or shGRM1, these studies were repeated in cells expressing high or low GRM1 levels where the gene was either silenced or overexpressed. Riluzole inhibited proliferation, invasion, and colony formation in both TNBC and ER+ cells. There was a trend between GRM1 expression in TNBC cells and their response to riluzole in both cell proliferation and invasion assays. However, silencing and overexpression studies had no effect on cell sensitivity to riluzole. Our results clearly suggest a GRM1-independent mechanism through which riluzole mediates its effects on breast cancer cells. Understanding the mechanism by which riluzole mediates breast cancer progression will be useful in identifying new therapeutic targets for treating TNBC and in facilitating stratification of patients in clinical trials using riluzole in conjunction with conventional therapy. PMID:27146584

  12. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shtutman Michael

    2010-04-01

    Full Text Available Abstract Background Castration resistant prostate cancer (CRPC develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881 restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to

  13. Low-cost piezoresistive silicon load cell independent of force distribution

    OpenAIRE

    Zwijze, Robert A.F.; Remco J. Wiegerink; Krijnen, Gijs J.M.; Lammerink, Theo S.J.; Elwenspoek, Miko

    1999-01-01

    A silicon load cell (force sensor) is presented which is based on a new operating principle. The force is measured by compressing a meander like strain gage. A second strain gage which is not loaded, is used for temperature compensation and for compensation of bending and stretching stresses in the chip. Also, same changes in zero load resistor values are eliminated. It is shown that the output of the bridge is a linear function of the total force and independent of the force distribution on ...

  14. Radiation could induce p53-independent and cell cycle - unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Didelot, C.; Mirjolet, J.F.; Barberi-Heyob, M.; Ramacci, C.; Merlin, J.L. [Centre Alexis Vautrin, Lab. de Recherche en Oncologie, Vandoeuvre-les-Nancy CEDEX (France)

    2002-07-01

    The effect of chemoresistance induction in radio sensitivity and cellular behavior after irradiation remains misunderstood. This study was designed to understand the relationship between radiation-induced cell cycle arrest, apoptosis, and radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil (5FU) exposure. Exposure of KB cells to 5FU led to an increase in radiosensitivity. G{sub 2}/M cell cycle arrest was observed in the two cell lines after irradiation. The radioresistant KB cell line reached the maximum arrest two hours before KB3. The cellular exit from this arrest was found to be related to the wild type p53 protein expression induction. After irradiation, only KB3 cell line underwent apoptosis. This apoptosis induction seemed to be independent of G{sub 2}/M arrest exit, which was carried out later. The difference in radiosensitivity between KB and KB3 subline may result therefore from both a difference in apoptosis induction and a difference in G{sub 2}/M arrest maximum duration. Moreover, 5FU exposure has led to an increase in constitutive p53 protein expression, which may be associated with an increase in basal apoptosis cell fraction. Given the existing correlation between radiosensitivity and the percentage of basal apoptosis. the constitutive p53 protein expression may be related to intrinsic radiosensitivity in our cellular model. (author)

  15. Predictive factors for perioperative blood transfusion in surgeries for correction of idiopathic, neuromuscular or congenital scoliosis

    Directory of Open Access Journals (Sweden)

    Alexandre Fogaça Cristante

    2014-12-01

    Full Text Available OBJECTIVE: To evaluate the association of clinical and demographic variables in patients requiring blood transfusion during elective surgery to treat scoliosis with the aim of identifying markers predictive of the need for blood transfusion. METHODS: Based on the review of medical charts at a public university hospital, this retrospective study evaluated whether the following variables were associated with the need for red blood cell transfusion (measured by the number of packs used during scoliosis surgery: scoliotic angle, extent of arthrodesis (number of fused levels, sex of the patient, surgery duration and type of scoliosis (neuromuscular, congenital or idiopathic. RESULTS: Of the 94 patients evaluated in a 55-month period, none required a massive blood transfusion (most patients needed less than two red blood cell packs. The number of packs was not significantly associated with sex or type of scoliosis. The extent of arthrodesis (r = 0.103, surgery duration (r = 0.144 and scoliotic angle (r = 0.004 were weakly correlated with the need for blood transfusion. Linear regression analysis showed an association between the number of spine levels submitted to arthrodesis and the volume of blood used in transfusions (p = 0.001. CONCLUSION: This study did not reveal any evidence of a significant association between the need for red blood cell transfusion and scoliotic angle, sex or surgery duration in scoliosis correction surgery. Submission of more spinal levels to arthrodesis was associated with the use of a greater number of blood packs.

  16. An Analysis of and Recommendations for the Peruvian Blood Collection and Transfusion System

    Science.gov (United States)

    George, Paul E; Vidal, Julio; Garcia, Patricia J

    2016-01-01

    Background Peru experienced a crisis in its blood collection and supply system in the mid-2000s, as contaminated blood led to several transfusion-transmitted infections (TTI), occurring in the backdrop of extremely low voluntary donation rates and a national blood supply shortage. Thus, the Peruvian Ministry of Health (MINSA) implemented a national investigation on the safety and quality of the Peruvian blood collection/transfusion network. Methods Every Peruvian blood bank was evaluated by MINSA from 2007–2008. These evaluations consisted of an update of the national registry of blood banks and visits to each blood bank from MINSA oversight teams. Information was collected on the condition of the blood bank personnel, equipment, supplies, and practices. Further, previously-collected blood at each blood bank was randomly selected and screened for TTI-causing pathogens. Results Uncovered in this investigation was a fragmented, under-equipped, and poorly-staffed blood collection and transfusion network, consisting of 241 independent blood banks and resulting in suboptimal allocation of resources. Further, blood with evidence of TTI-causing pathogens (including Hepatitis B, Hepatitis C, and syphilis) and set for transfusion was discovered at three separate blood banks as part of the random screening process. Conclusion Using the successful reorganizations of national blood supply systems in other Latin American countries as examples, Peru would be well-served to form large, high-volume, regional blood collection and transfusion centers, responsible for blood collection and screening for the entire country. The small, separate blood banks would then be transformed into a network of blood transfusion centers, not responsible for blood collection. This reorganization would allow Peru to better utilize its resources, standardize the blood collection and transfusion process, and increase voluntary donation, resulting in a safer, more abundant national blood product.

  17. Agarol, an ergosterol derivative from Agaricus blazei, induces caspase-independent apoptosis in human cancer cells.

    Science.gov (United States)

    Shimizu, Takamitsu; Kawai, Junya; Ouchi, Kenji; Kikuchi, Haruhisa; Osima, Yoshiteru; Hidemi, Rikiishi

    2016-04-01

    Agaricus blazei (A. blazei) is a mushroom with many biological effects and active ingredients. We purified a tumoricidal substance from A. blazei, an ergosterol derivative, and named it 'Agarol'. Cytotoxic effects of Agarol were determined by the MTT assay using A549, MKN45, HSC-3, and HSC-4 human carcinoma cell lines treated with Agarol. Apoptosis was detected by flow cytometry analysis. Reactive oxygen species (ROS) levels and mitochondria membrane potential (∆ψm) were also determined by flow cytometry. Western blot analysis was used to quantify the expression of apoptosis-related proteins. Agarol predominantly induced apoptosis in two p53-wild cell lines (A549 and MKN45) compared to the other p53-mutant cell lines (HSC-3 and HSC-4). Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of ROS, reduced ∆ψm, release of apoptosis-inducing factor (AIF) from the mitochondria to the cytosol, upregulation of Bax, and downregulation of Bcl-2. Caspase-3 activities did not increase, and z-VAD-fmk, a caspase inhibitor, did not inhibit the Agarol-induced apoptosis. These findings indicate that Agarol induces caspase-independent apoptosis in human carcinoma cells through a mitochondrial pathway. The in vivo anticancer activity of Agarol was confirmed in a xenograft murine model. This study suggests a molecular mechanism by which Agarol induces apoptosis in human carcinoma cells and indicates the potential use of Agarol as an anticancer agent. PMID:26893131

  18. Phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by carbon nanotube agglomerates.

    Science.gov (United States)

    Shigemoto-Mogami, Yukari; Hoshikawa, Kazue; Hirose, Akihiko; Sato, Kaoru

    2016-01-01

    Although carbon nanotubes (CNTs) are used in many fields, including energy, healthcare, environmental technology, materials, and electronics, the adverse effects of CNTs in the brain are poorly understood. In this study, we investigated the effects of CNTs on cultured microglia, as microglia are the first responders to foreign materials. We compared the effects of sonicated suspensions of 5 kinds of CNTs and their flow-through filtered with a 0.22 µm membrane filter on microglial viability. We found that sonicated suspensions caused microglial cell damage, but their flow-through did not. The number of microglial aggregates was well correlated with the extent of the damage. We also determined that the CNT agglomerates consisted of two groups: one was phagocytosed by microglia and caused microglial cell damage, and the other caused cell damage without phagocytosis. These results suggest that phagocytosis-dependent and independent mechanisms underlie the microglial cell damage caused by CNT agglomerates and it is important to conduct studies about the relationships between physical properties of nanomaterial-agglomerates and cell damage. PMID:27432236

  19. Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.

    Science.gov (United States)

    Huang, Jong-Khing; Huang, Chun-Jen; Chen, Wei-Chuan; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Tseng, Li-Ling; Chou, Chiang-Ting; Chang, Chih-Hung; Jan, Chung-Ren

    2005-07-01

    The effect of the carcinogen safrole on intracellular Ca2+ movement and cell proliferation has not been explored previously. The present study examined whether safrole could alter Ca2+ handling and growth in human oral cancer OC2 cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at a concentration of 325 microM started to increase [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 40% by removing extracellular Ca2+, and was decreased by 39% by nifedipine but not by verapamil or diltiazem. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) barely induced a [Ca2+]i rise; in contrast, addition of safrole after thapsigargin treatment induced a small [Ca2+]i rise. Neither inhibition of phospholipase C with 2 microM U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 1 microM safrole did not alter cell proliferation, but incubation with 10-1000 microM safrole increased cell proliferation by 60+/-10%. This increase was not reversed by pre-chelating Ca2+ with 10 microM of the Ca2+ chelator BAPTA. Collectively, the data suggest that in human oral cancer cells, safrole induced a [Ca2+]i rise by causing release of stored Ca2+ from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx via nifedipine-sensitive Ca2+ entry. Furthermore, safrole can enhance cell growth in a Ca2+-independent manner.

  20. Replication independent formation of extrachromosomal circular DNA in mammalian cell-free system.

    Directory of Open Access Journals (Sweden)

    Zoya Cohen

    Full Text Available Extrachromosomal circular DNA (eccDNA is a pool of circular double stranded DNA molecules found in all eukaryotic cells and composed of repeated chromosomal sequences. It was proposed to be involved in genomic instability, aging and alternative telomere lengthening. Our study presents novel mammalian cell-free system for eccDNA generation. Using purified protein extract we show that eccDNA formation does not involve de-novo DNA synthesis suggesting that eccDNA is generated through excision of chromosomal sequences. This process is carried out by sequence-independent enzymes as human protein extract can produce mouse-specific eccDNA from high molecular weight mouse DNA, and vice versa. EccDNA production does not depend on ATP, requires residual amounts of Mg(2+ and is enhanced by double strand DNA breaks.

  1. P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells.

    Science.gov (United States)

    Chen, Lihui; Jiang, Jianming; Cheng, Chunlei; Yang, Ajing; He, Qiyang; Li, Diandong; Wang, Zhen

    2007-06-01

    Enediyne compound is one class of antibiotics with very potent anti-cancer activity. However, the role of p53 in enediyne antibiotic-induced cell killing remains elusive. Here we reported the involvement of p53 signaling pathway in apoptosis induction by lidamycin (LDM), a member of the enediyne antibiotic family. We found that LDM at low drug concentration of 10 nmol/L induces apoptotic cell death much more effectively in human colorectal cancer cells with wild type p53 than those with mutant or deleted p53. p53 is functionally activated as an early event in response to low dose LDM that precedes the significant apoptosis induction. The primarily activation of mitochondria as well as the activation of p53 transcriptional targets such as Puma, Bad and Bax in HCT116 p53 wild type cells further demonstrates the key role of p53 in mediating the compound-induced apoptosis. This is further supported by the observation that the absence of Bax or Puma decreases apoptosis dramatically while Bcl-2 overexpression confers partially resistance after drug treatment. Activation of p53 signaling pathway leads to activation of caspases and caspases inhibitor VAD-fmk completely blocks low dose LDM induced apoptosis through the inhibition of mitochondria pathway. In contrast, LDM at higher concentration causes rapid apoptosis through more direct DNA damaging mechanism that is independent of activation of p53 and caspases and cannot be blocked by caspase inhibitor. Taken together, LDM induces apoptosis in a p53-dependent manner when given at low doses, but in a p53-independent manner when given at high doses. This dosage-dependent regimen can be applied to cancer clinic based upon the p53 status of cancer patients. PMID:17534142

  2. Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Alexandre Henriques

    Full Text Available Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS. Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R, survival, disease duration, site of onset and body mass index. Palmitoleate (16:1 and oleate (18:1 levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0 significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05. Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009. In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

  3. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment.

  4. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment. PMID:26872600

  5. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

    Institute of Scientific and Technical Information of China (English)

    Hongliang Wang; Peng Yang; Kangtai Liu; Feng Guo; Yanli Zhang; Gongyi Zhang; Chengyu Jiang

    2008-01-01

    While severe acute respiratory syndrome coronavirus (SARS-CoV)fwas initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. We have found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis. Treatment of cells with either SARS-CoV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic pathway inhibitors and dominant-negative Eps15 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

  6. Inflammasome-independent modulation of cytokine response by autophagy in human cells.

    Directory of Open Access Journals (Sweden)

    Tania O Crişan

    Full Text Available Autophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 deficient mice have shown that disruption of autophagy increases processing of IL-1β and IL-18 through an inflammasome-dependent manner. Using complementary approaches either inducing or inhibiting autophagy, we describe modulatory effects of autophagy on proinflammatory cytokine production in human cells. Inhibition of basal autophagy in human peripheral blood mononuclear cells (PBMCs significantly enhances IL-1β after stimulation with TLR2 or TLR4 ligands, while at the same time reducing the production of TNFα. In line with this, induction of autophagy by starvation inhibited IL-1β production. These effects of autophagy were not exerted at the processing step, as inflammasome activation was not influenced. In contrast, the effect of autophagy on cytokine production was on transcription level, and possibly involving the inhibition of p38 mitogen activated protein kinase (MAPK phosphorylation. In conclusion, autophagy modulates the secretion of proinflammatory cytokines in human cells through an inflammasome-independent pathway, and this is a novel mechanism that may be targeted in inflammatory diseases.

  7. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.

    Science.gov (United States)

    Ambrosini, Grazia; Sawle, Ashley D; Musi, Elgilda; Schwartz, Gary K

    2015-10-20

    Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth.Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations. PMID:26397223

  8. Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance.

    Science.gov (United States)

    Gong, Jingyi; Körner, Roman; Gaitanos, Louise; Klein, Rüdiger

    2016-07-01

    The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2(+) EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2(+) EVs in neural development and synapse physiology. PMID:27354374

  9. Transfusion and blood donation in comic strips.

    Science.gov (United States)

    Lefrère, Jean-Jacques; Danic, Bruno

    2013-07-01

    The representation of blood transfusion and donation of blood in the comic strip has never been studied. The comic strip, which is a relatively recent art, emerged in the 19th century before becoming a mass medium during the 20th century. We have sought, by calling on collectors and using the resources of Internet, comic strips devoted, wholly or in part, to the themes of transfusion and blood donation. We present some of them here in chronologic order, indicating the title, country of origin, year of publication, and names of authors. The theme of the superhero using transfusion to transmit his virtues or his powers is repeated throughout the 20th century in North American comic strips. More recently, comic strips have been conceived from the outset with a promotional aim. They perpetuate positive images and are directed toward a young readership, wielding humor to reduce the fear of venipuncture. Few comic strips denounce the abuse of the commercialization of products derived from the human body. The image of transfusion and blood donation given by the comic strips is not to be underestimated because their readership is primarily children, some of whom will become blood donors. Furthermore, if some readers are transfused during their lives, the impact of a memory more or less conscious of these childhood readings may resurface, both in hopes and in fears.

  10. Radiation induced bystander signals are independent of DNA damage and DNA repair capacity of the irradiated cells

    International Nuclear Information System (INIS)

    Evidence is accumulating that irradiated cells produce signals, which interact with non-exposed cells in the same population. Here, we analysed the mechanism for bystander signal arising in wild-type CHO cells and repair deficient varients, focussing on the relationship between DNA repair capacity and bystander signal arising in irradiated cells. In order to investigate the bystander effect, we carried out medium transfer experiments after X-irradiation where micronuclei were scored in non-targeted DSB repair deficient xrs5 cells. When conditioned medium from irradiated cells was transferred to unirradiated xrs5 cells, the level of induction was independent of whether the medium came from irradiated wild-type, ssb or dsb repair deficient cells. This result suggests that the activation of a bystander signal is independent of the DNA repair capacity of the irradiated cells. Also, pre-treatment of the irradiated cells with 0.5% DMSO, which suppresses micronuclei induction in CHO but not in xrs5 cells, suppressed bystander effects completely in both conditioned media, suggesting that DMSO is effective for suppression of bystander signal arising independently of DNA damage in irradiated cells. Overall the work presented here adds to the understanding that it is the repair phenotype of the cells receiving bystander signals, which determines overall response rather than that of the cell producing the bystander signal

  11. HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer.

    Directory of Open Access Journals (Sweden)

    Hong Jian Xie

    Full Text Available Histone deacetylases (HDACs are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC, but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1 and p27(Kip1 expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1 transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1 promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.

  12. Biomechanics of P-selectin PSGL-1 bonds: Shear threshold and integrin-independent cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Zhihua; Goldsmith, Harry L.; MacIntosh, Fiona A.; Shankaran, Harish; Neelamegham, Sriram

    2006-03-01

    Platelet-leukocyte adhesion may contribute to thrombosis and inflammation. We examined the heterotypic interaction between unactivated neutrophils and either thrombin receptor activating peptide (TRAP) stimulated platelets or P-selectin bearing beads (Ps-beads) in suspension. Cone-plate viscometers were used to apply controlled shear rates from 14-3000/s. Platelet-neutrophil and bead-neutrophil adhesion analysis was performed using both flow cytometry and high-speed videomicroscopy. We observed that while blocking antibodies against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1) alone inhibited platelet-neutrophil adhesion by ~60% at 140/s, these reagents completely blocked adhesion at 3000/s. Anti-Mac-1 alone did not alter platelet-neutrophil adhesion rates at any shear rate, though in synergy with selectin antagonists it abrogated cell binding. Unstimulated neutrophils avidly bound Ps-beads and activated platelets in an integrin-independent manner, suggesting that purely selectin-dependent cell adhesion is possible. In support of this, antagonists against P-selectin or PSGL-1 dissociated previously formed platelet-neutrophil and Ps-bead neutrophil aggregates under shear in a variety of experimental systems, including in assays performed with whole blood. In studies where medium viscosity and shear rate were varied, a subtle shear threshold for P-selectin PSGL-1 binding was also noted at shear rates<100/s and at force loading rates of ~300pN/sec. Results are discussed in light of biophysical computations that characterize the collision between unequal size particles in linear shear flow. Overall, our studies reveal an integrin-independent regime for cell adhesion that may be physiologically relevant.

  13. Human regulatory T cell suppressive function is independent of apoptosis induction in activated effector T cells.

    Directory of Open Access Journals (Sweden)

    Yvonne Vercoulen

    Full Text Available BACKGROUND: CD4(+CD25(+FOXP3(+ Regulatory T cells (Treg play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff responses by deprivation of the growth factor IL-2 through Treg consumption, resulting in apoptosis of Teff. PRINCIPAL FINDINGS: In this study we investigated the relevance of Teff apoptosis induction to human Treg function. To this end, we studied naturally occurring Treg (nTreg from peripheral blood of healthy donors, and, to investigate Treg function in inflammation in vivo, Treg from synovial fluid of Juvenile Idiopathic Arthritis (JIA patients (SF-Treg. Both nTreg and SF-Treg suppress Teff proliferation and cytokine production efficiently as predicted. However, in contrast with murine Treg, neither nTreg nor SF-Treg induce apoptosis in Teff. Furthermore, exogenously supplied IL-2 and IL-7 reverse suppression, but do not influence apoptosis of Teff. SIGNIFICANCE: Our functional data here support that Treg are excellent clinical targets to counteract autoimmune diseases. For optimal functional outcome in human clinical trials, future work should focus on the ability of Treg to suppress proliferation and cytokine production of Teff, rather than induction of Teff apoptosis.

  14. A Case of Transfusion Error in a Trauma Patient With Subsequent Root Cause Analysis Leading to Institutional Change.

    Science.gov (United States)

    Clifford, Sean Patrick; Mick, Paul Brian; Derhake, Brian Matthew

    2016-01-01

    A 28-year-old man presented emergently to the operating room following a gun-shot injury to his right groin. Our hospital's Massive Transfusion Protocol was initiated as the patient entered the operating room actively hemorrhaging and severely hypotensive. During the aggressive resuscitation efforts, the patient was inadvertently transfused 2 units of packed red blood cells intended for another patient due to a series of errors. Fortunately, the incorrect product was compatible, and the patient recovered from his near-fatal injuries. Root cause analysis was used to review the transfusion error and develop an action plan to help prevent future occurrences. PMID:27231693

  15. T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles

    OpenAIRE

    Fehr, Thomas; Skrastina, Dace; Pumpens, Paul; Zinkernagel, Rolf M.

    1998-01-01

    Recombinant viral or virus-like particles offer new tools for vaccine development. This study investigated hepatitis B core antigen (HBcAg) capsids and RNA phage Qβ coats as carriers of a foreign epitope to induce antibody responses in mice. HBcAg capsids were shown to induce T cell-independent (TI) antibodies. We found that these particles behave as antigen-specific TI type 1 (TI-1) Ag comparable to other rigidly structured viruses. When a 5-aa long epitope of the pre-S1 domain of hepatitis ...

  16. Diagnosis of Beta-thalassaemia major in previously transfused patients

    International Nuclear Information System (INIS)

    Objective: The study was conducted to evaluate the effects of blood transfusion(s) on the haematological picture of beta-thalassaemia major. Results: Out of the 280 patients 109 (39%) had received one or more blood transfusions (cases). The remaining 171 patients who did not receive any transfusion served as controls. The mean MCV, MCH and Hb-F in cases were significantly higher than in the controls (p4 transfusions (17%) (p=0.016). In the occasionally transfused patients Hb-F level was directly related to the time since last transfusion. In 44/109 (40%) transfused patients (Hb-F>30%) the diagnosis of thalassaemia was not difficult. In 54/109 (50%) patients (Hb-:5-30%) the diagnosis was aided by parent's study, while PCR for thalassaemia mutation was required in 11/109 (10%) patients (Hb-F <5%). Conclusion: In most transfused patients of thalassaemia major MCV and MCH were significantly higher while Hb-F was lower than in the un-transfused patients. There was a linear correlation between Hb-F level and time since last transfusion in the occasionally transfused patients. However, the reduction in Hb-F level was more marked and sustained in multipally transfused patients. Parent's study and PCR are useful aids in establishing the correct diagnosis in these patients. (author)

  17. A Systematic Review and Meta-Analysis of the Clinical Appropriateness of Blood Transfusion in China.

    Science.gov (United States)

    Zhu, Changtai; Gao, Yulu; Li, Zhiqiang; Li, Qinyun; Gao, Zongshuai; Liao, Yanqiu; Deng, Zhifeng

    2015-12-01

    The issue of the clinical appropriateness of blood transfusion has become a focus of transfusion medicine worldwide. In China, irrational uses of blood have often been reported in recent years. However, to date there lacks a systematic review of the rational uses of blood. This study aimed to determine the clinical appropriateness of blood transfusion in China. We searched PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and Chinese BioMedical Literature Database, and the retrieval cut-off date was June 31, 2015. SPSS 17.0 and MetaAnalyst 3.13 were employed as the statistics tools in this review. A pooled rate of clinical inappropriateness of transfusion was analyzed by DerSimonian-Laird method. In this study, a total of 39 observational studies were included, which related to 75,132 cases of blood transfusion. According to the meta-analysis results, the overall incidence of clinical inappropriateness of transfusion in China was estimated to be 37.3% (95% confidence interval [CI] [32.1, 42.8]). The subgroup analyses revealed that the pooled rates of clinical inappropriateness of transfusion of plasma, red blood cells (RBCs), cryoprecipitate, and platelets were 56.3% (95% CI [45.8, 66.2]), 30.9% (95% CI [27.1, 35.0]), 25.2% (95% CI [13.2, 42.7]), and 14.1% (95% CI [8.8, 21.9]), respectively. However, the pooled incidence of inappropriateness of transfusion in operative departments was 47.5% (95% CI [36.8, 58.3]), which was significantly higher than that in nonoperative departments, 25.8% (95% CI [18.7, 34.4], P  0.05). In conclusion, China has suffered from a disadvantage in the clinical appropriateness of blood transfusion, especially in plasma and RBC use. In future, comprehensive measures should be implemented in order to improve the clinical appropriateness of blood transfusion.

  18. A multicentre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and health-care resource use following cardiac surgery (TITRe2).

    Science.gov (United States)

    Reeves, Barnaby C; Pike, Katie; Rogers, Chris A; Brierley, Rachel Cm; Stokes, Elizabeth A; Wordsworth, Sarah; Nash, Rachel L; Miles, Alice; Mumford, Andrew D; Cohen, Alan; Angelini, Gianni D; Murphy, Gavin J

    2016-01-01

    BACKGROUND Uncertainty about optimal red blood cell transfusion thresholds in cardiac surgery is reflected in widely varying transfusion rates between surgeons and cardiac centres. OBJECTIVE To test the hypothesis that a restrictive compared with a liberal threshold for red blood cell transfusion after cardiac surgery reduces post-operative morbidity and health-care costs. DESIGN Multicentre, parallel randomised controlled trial and within-trial cost-utility analysis from a UK NHS and Personal Social Services perspective. We could not blind health-care staff but tried to blind participants. Random allocations were generated by computer and minimised by centre and operation. SETTING Seventeen specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS Patients aged > 16 years undergoing non-emergency cardiac surgery with post-operative haemoglobin research steps to address the new hypothesis about the possible harm of red blood cell transfusion. TRIAL REGISTRATION Current Controlled Trials ISRCTN70923932. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 60. See the NIHR Journals Library website for further project information. PMID:27527344

  19. Where are the systematic reviews in transfusion medicine? A study of the transfusion evidence base.

    Science.gov (United States)

    Dorée, Carolyn; Stanworth, Simon; Brunskill, Susan J; Hopewell, Sally; Hyde, Chris J; Murphy, Mike F

    2010-10-01

    Transfusion medicine has become a large and complex specialty. Although there are now systematic reviews covering many aspects of transfusion, these span a large number of clinical areas and are published across more than a hundred different medical journals, making it difficult for transfusion medicine practitioners and researchers to keep abreast of the current high-level evidence. In response to this problem, NHS Blood and Transplant's Systematic Review Initiative (SRI) has produced a comprehensive overview of systematic reviews in transfusion medicine. A systematic search (to December 2009) and screening procedure were followed by the appraisal of systematic reviews according to predefined inclusion criteria. The 340 eligible systematic reviews were mapped to 10 transfusion intervention groups and 14 topic groups within clinical medicine. Trends in the systematic review literature were examined and gaps in the literature described. The spread of systematic reviews across clinical areas was found to be very uneven, with some areas underreviewed and others with multiple systematic reviews on the same topic, making the identification of the best evidence for current transfusion practice a continuing challenge. References and links to all systematic reviews included in this overview can be freely accessed via the SRI's new online database, the Transfusion Evidence Library (www.transfusionguidelines.org). PMID:20851331

  20. Regulatory T cells and IL-10 independently counterregulate cytotoxic T lymphocyte responses induced by transcutaneous immunization.

    Directory of Open Access Journals (Sweden)

    Pamela Stein

    Full Text Available BACKGROUND: The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI. Here we investigated the role of regulatory T cells (T(reg and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL responses. METHODOLOGY/PRINCIPAL FINDINGS: TCI was performed with an ointment containing the TLR7 agonist imiquimod and a CTL epitope was applied to the depilated back skin of C57BL/6 mice. Using specific antibodies and FoxP3-diphteria toxin receptor transgenic (DEREG mice, we interrogated inhibiting factors after TCI: by depleting FoxP3(+ regulatory T cells we found that specific CTL-responses were greatly enhanced. Beyond this, in IL-10 deficient (IL-10(-/- mice or after blocking of IL-10 signalling with an IL-10 receptor specific antibody, the TCI induced CTL response is greatly enhanced indicating an important role for this cytokine in TCI. However, by transfer of T(reg in IL-10(-/- mice and the use of B cell deficient JHT(-/- mice, we can exclude T(reg and B cells as source of IL-10 in the setting of TCI. CONCLUSION/SIGNIFICANCE: We identify T(reg and IL-10 as two important and independently acting suppressors of CTL-responses induced by transcutaneous immunization. Advanced vaccination strategies inhibiting T(reg function and IL-10 release may lead the development of effective vaccination protocols aiming at the induction of T cell responses suitable for the prophylaxis or treatment of persistent infections or tumors.

  1. Nitric oxide decreases intestinal haemorrhagic lesions in rat anaphylaxis independently of mast cell activation

    Directory of Open Access Journals (Sweden)

    J. Carvalho Tavares

    1997-01-01

    Full Text Available The purpose of this study is to assess the role of nitric oxide (NO in the intestinal lesions of passive anaphylaxis, since this experimental model resembles necrotizing enterocolitis. Sprague-Dawley rats were sensitized with IgE anti-dinitrophenol monoclonal antibody. Extravasation of protein-rich plasma and haemorrhagia were measured in the small intestine. Plasma histamine was measured to assess mast cell activation. The effect of exogenous NO on the lesions was assessed by using two structurally unrelated NO-donors: sodium nitroprusside and S-nitroso-Nacetyl-penicillamine (SNAP. An increased basal production of NO was observed in cells taken after anaphylaxis, associated with a reduced response to platelet-activating factor, interleukin 1beta, and IgE/DNP-bovine serum albumin complexes. The response to bacterial lipopolysaccharide and dibutyryl cyclic adenosine monophosphate (AMP was enhanced 24 h after challenge, but at earlier times was not significantly different from that observed in controls. Treatment with either sodium nitroprusside or SNAP produced a significant reduction of the haemorrhagic lesions, which are a hallmark of rat anaphylaxis. The extravasation of protein-rich plasma was not influenced by NO-donors. The increase of plasma histamine elicited by the anaphylactic challenge was not influenced by SNAP treatment. NO-donors protect intestinal haemorrhagic lesions of rat anaphylaxis by a mechanism apparently independent of mast cell histamine release.

  2. Circulation-Independent Differentiation Pathway from Extraembryonic Mesoderm toward Hematopoietic Stem Cells via Hemogenic Angioblasts

    Directory of Open Access Journals (Sweden)

    Yosuke Tanaka

    2014-07-01

    Full Text Available A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs. Previously, we reported that Runx1+ cells in embryonic day 7.5 (E7.5 embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM region and HSCs in the adult bone marrow. Here, we show that two Runx1+ populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1+Gata1− population. A subset of this population moves from the extra- to intraembryonic region during E7.5–E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA. Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1+ cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.

  3. Tuning 3D Collagen Matrix Stiffness Independently of Collagen Concentration Modulates Endothelial Cell Behavior

    Science.gov (United States)

    Mason, Brooke N.; Starchenko, Alina; Williams, Rebecca M.; Bonassar, Lawrence J.; Reinhart-King, Cynthia A.

    2012-01-01

    Numerous studies have described the effects of matrix stiffening on cell behavior using two dimensional (2D) synthetic surfaces; however less is known about the effects of matrix stiffening on cells embedded in three dimensional (3D) in vivo-like matrices. A primary limitation in investigating the effects of matrix stiffness in 3D is the lack of materials that can be tuned to control stiffness independently of matrix density. Here, we use collagen-based scaffolds where the mechanical properties are tuned using non-enzymatic glycation of the collagen in solution, prior to polymerization. Collagen solutions glycated prior to polymerization result in collagen gels with a 3-fold increase in compressive modulus without significant changes to the collagen architecture. Using these scaffolds, we show that endothelial cell spreading increases with matrix stiffness, as does the number and length of angiogenic sprouts and the overall spheroid outgrowth. Differences in sprout length are maintained even when the receptor for advanced glycation endproducts is inhibited. Our results demonstrate the ability to de-couple matrix stiffness from matrix density and structure in collagen gels, and that increased matrix stiffness results in increased sprouting and outgrowth. PMID:22902816

  4. The impact of storage time of transfused blood on postoperative infectious complications in rectal cancer surgery. Danish RANX05 Colorectal Cancer Study Group

    DEFF Research Database (Denmark)

    Mynster, T; Nielsen, Hans Jørgen

    2000-01-01

    BACKGROUND: We have studied the impact of storage time of transfused allogeneic blood together with other known risk factors on postoperative infectious complications after operation for rectal cancer. METHODS: Intra-abdominal abscess, anastomotic leakage, septicaemia, wound infection...... and storage time of saline-adenine-glucose-mannitol (SAGM) blood, administered to each patient, were recorded retrospectively. RESULTS: The overall infection rate was 24% in 78 non-transfused and 40% in 225 transfused patients (P = 0.011). The proportion of SAGM blood stored for > or = 21 days administered...... days (odds ratio, 2.5 versus no transfusion) to be independent variables predicting infectious complications. CONCLUSION: Blood storage time may, along with other risk factors, play a significant role in blood transfusion-associated development of postoperative infectious complications....

  5. ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1.

    Directory of Open Access Journals (Sweden)

    Eyal Kalie

    Full Text Available Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis.

  6. Platelet Transfusion and Thrombosis: More Questions than Answers.

    Science.gov (United States)

    Schmidt, Amy E; Refaai, Majed A; Blumberg, Neil

    2016-03-01

    Platelets perform a vital role in hemostasis and their role in inflammation is becoming increasingly evident. Blood transfusion is the most common procedure performed in hospitals and platelet transfusions comprise a significant proportion. Over the past few decades, retrospective studies and randomized clinical trials have demonstrated that blood transfusion is more harmful than previously thought and is associated with numerous complications, such as transfusion-associated lung injury, transfusion-associated cardiac overload, transfusion-associated immune modulation, and infectious diseases such as human immunodeficiency virus, hepatitis C virus, and hepatitis B virus. Recent data suggest an association between platelet transfusion and thrombosis. This review will highlight the mechanistic issues that may be relevant to the epidemiologic associations of platelet transfusion with thrombosis and mortality in critically ill patients. PMID:26716501

  7. Association of blood transfusion with increased mortality in myocardial infarction

    DEFF Research Database (Denmark)

    Chatterjee, Saurav; Wetterslev, Jørn; Sharma, Abhishek;

    2013-01-01

    The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists.......The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists....

  8. Cell Wall Invertase Promotes Fruit Set under Heat Stress by Suppressing ROS-Independent Cell Death1[OPEN

    Science.gov (United States)

    2016-01-01

    Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop production, by using transgenic tomato (Solanum lycopersicum) with its CWIN inhibitor gene silenced and focusing on ovaries and fruits at 2 d before and after pollination, respectively. We found that the increase of CWIN activity suppressed LMHS-induced programmed cell death in fruits. Surprisingly, measurement of the contents of H2O2 and malondialdehyde and the activities of a cohort of antioxidant enzymes revealed that the CWIN-mediated inhibition on programmed cell death is exerted in a reactive oxygen species-independent manner. Elevation of CWIN activity sustained Suc import into fruits and increased activities of hexokinase and fructokinase in the ovaries in response to LMHS. Compared to the wild type, the CWIN-elevated transgenic plants exhibited higher transcript levels of heat shock protein genes Hsp90 and Hsp100 in ovaries and HspII17.6 in fruits under LMHS, which corresponded to a lower transcript level of a negative auxin responsive factor IAA9 but a higher expression of the auxin biosynthesis gene ToFZY6 in fruits at 2 d after pollination. Collectively, the data indicate that CWIN enhances fruit set under LMHS through suppression of programmed cell death in a reactive oxygen species-independent manner that could involve enhanced Suc import and catabolism, HSP expression, and auxin response and biosynthesis. PMID:27462084

  9. Acute hemolytic transfusion reactions due to multiple alloantibodies including anti-E, anti-c and anti-Jkb.

    Science.gov (United States)

    Park, Tae Sung; Kim, Ki Uk; Jeong, Woo Jin; Kim, Hyung Hoi; Chang, Chulhun L; Chung, Joo Seop; Cho, Goon Jae; Lee, Eun Yup; Son, Han Chul

    2003-12-01

    We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients. PMID:14676451

  10. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    Directory of Open Access Journals (Sweden)

    Rana Baraz

    Full Text Available Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

  11. The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner

    OpenAIRE

    Jiwen Cheng; Keqin Yang; Qingyun Zhang; Yang Yu; Qinggui Meng; Ning Mo; Yang Zhou; Xianlin Yi; Chengzhong Ma; Aming Lei; Yan Liu

    2016-01-01

    Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. Firstly, we demonstrated that MSCs could affect the transformation of androgen-dependent human PCa ce...

  12. Unexpected effects of transfusion in the critically ill

    OpenAIRE

    Straat, M.

    2016-01-01

    Since the first recorded successful blood transfusion was performed in 1665 and the first Intensive Care Unit (ICU) was founded in 1952, a transfusion has gradually become a common medical procedure in the ICU. However, recent studies have shown an association between transfusion and adverse outcome. This thesis contains both clinical and pre-clinical investigations of the effects of a transfusion in the critically ill. The studies focus on investigations of mechanisms of the association betw...

  13. Risk factors and outcomes in transfusion-associated circulatory overload

    OpenAIRE

    Murphy, EL; Kwaan, N; Looney, MR; Gajic, O; Hubmayr, RD; Gropper, MA; Koenigsberg, M; Wilson, G.; Matthay, M; Bacchetti, P.; Toy, P

    2013-01-01

    Background: Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. Methods: Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic ...

  14. Transfusion-related acute lung injury:A case report

    Institute of Scientific and Technical Information of China (English)

    Emmanouil Petrou; Vasiliki Karali; Vasiliki Vartela

    2015-01-01

    Transfusion-related acute lung injury is the most common cause of serious morbidity and mortality associated with the transfusion of plasma-containing blood components. The syndrome can be confused with other causes of acute respiratory failure. Herein, we describe a 71-year-old man who was transfused with fresh frozen plasma due to prolonged INR, and died of what was considered as transfusion-related acute lung injury, despite treatment.

  15. Adverse blood transfusion reactions at tertiary care hospital

    OpenAIRE

    Surekha K. Chavan; Gorakhnath Patil; Pallavi Rajopadhye

    2016-01-01

    Background: The goal of hemovigilance is to increase the safety and quality of blood transfusion. It is necessary to recognize and prompt response to adverse transfusion reactions, which will help in taking appropriate steps to reduce their incidence and make blood transfusion process as safe as possible. The aim of the study was to determine the frequency and type of transfusion reactions (TRs) occurring in patients, reported to the blood bank at our institute. Methods: A retrospective r...

  16. Polarization of migrating monocytic cells is independent of PI 3-kinase activity.

    Directory of Open Access Journals (Sweden)

    Silvia Volpe

    Full Text Available BACKGROUND: Migration of mammalian cells is a complex cell type and environment specific process. Migrating hematopoietic cells assume a rapid amoeboid like movement when exposed to gradients of chemoattractants. The underlying signaling mechanisms remain controversial with respect to localization and distribution of chemotactic receptors within the plasma membrane and the role of PI 3-kinase activity in cell polarization. METHODOLOGY/PRINCIPAL FINDINGS: We present a novel model for the investigation of human leukocyte migration. Monocytic THP-1 cells transfected with the alpha(2A-adrenoceptor (alpha(2AAR display comparable signal transduction responses, such as calcium mobilization, MAP-kinase activation and chemotaxis, to the noradrenaline homologue UK 14'304 as when stimulated with CCL2, which binds to the endogenous chemokine receptor CCR2. Time-lapse video microscopy reveals that chemotactic receptors remain evenly distributed over the plasma membrane and that their internalization is not required for migration. Measurements of intramolecular fluorescence resonance energy transfer (FRET of alpha(2AAR-YFP/CFP suggest a uniform activation of the receptors over the entire plasma membrane. Nevertheless, PI 3-kinase activation is confined to the leading edge. When reverting the gradient of chemoattractant by moving the dispensing micropipette, polarized monocytes--in contrast to neutrophils--rapidly flip their polarization axis by developing a new leading edge at the previous posterior side. Flipping of the polarization axis is accompanied by re-localization of PI-3-kinase activity to the new leading edge. However, reversal of the polarization axis occurs in the absence of PI 3-kinase activation. CONCLUSIONS/SIGNIFICANCE: Accumulation and internalization of chemotactic receptors at the leading edge is dispensable for cell migration. Furthermore, uniformly distributed receptors allow the cells to rapidly reorient and adapt to changes in the

  17. Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent.

    Science.gov (United States)

    Kamiyama, Haruka; Kakoki, Katsura; Yoshii, Hiroaki; Iwao, Masatomo; Igawa, Tsukasa; Sakai, Hideki; Hayashi, Hideki; Matsuyama, Toshifumi; Yamamoto, Naoki; Kubo, Yoshinao

    2011-01-01

    Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.

  18. 42 CFR 493.1103 - Standard: Requirements for transfusion services.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Requirements for transfusion services... Administration for Nonwaived Testing § 493.1103 Standard: Requirements for transfusion services. A facility that provides transfusion services must meet all of the requirements of this section and document...

  19. DEL RBC transfusion should be avoided in particular blood recipient in East Asia due to allosensitization and ineffectiveness

    Institute of Scientific and Technical Information of China (English)

    Chao-peng SHAO; Bao-yan WANG; Shi-hui YE; Wen-li ZHANG; Hua XU; Nai-bao ZHUANG; Xiao-ying WU; Heng-gui XU

    2012-01-01

    Previously,both primary and secondary anti-D alloimmunizations induced by “Asian type" DEL (RHD1227A allele) were observed in two incidents.We investigated how often these alloimmunization events occur.The transfusions of any D-negative patients were investigated in the First Affiliated Hospital of Xi'an Jiaotong University Medical College,China,during the entire 2009.The antigens of D,C,c,E,and e were routinely serotyped.The "Asian type" DEL variant was genotyped and the RHD heterozygote was determined through two published methods.The changes in anti-D levels were monitored by the indirect antiglobulin test (IAT) and flow cytometry.Thirty D-negative transfused patients were included in the study.We focused on 11 recipients who were transfused with packed red blood cells (RBCs) from DEL donors at least one time.Of those 11 recipients,seven were anti-D negative before transfusion and four were anti-D positive (one patient with an autoantibody).One of the seven pre-transfusion anti-D negative patients produced a primary-response anti-D after being transfused with 400 ml of DEL blood twice.All four pre-transfusion antibody positive patients were not observed hemoglobin (Hb) levels increased,as expected after transfusions.Two patients had an increase in anti-D from 1∶8 to 1∶64 by IAT,which was also shown by flow cytometry.None of the patients experienced an acute hemolytic episode.Our data indicated that the primary anti-D induced by DEL transfusion or the secondary anti-D elevated by DEL in a truly D-negative patient might not be unusual.We suggest that a truly D-negative childbearing-aged woman should avoid DEL transfusion to protect her from primary anti-D allosensitization.In addition,anti-D positive recipients should also avoid DEL red cell transfusion due to the delayed hemolytic transfusion reaction (DHTR).

  20. Conditioning out-of-date bank-stored red blood cells using a cell-saver auto-transfusion device: effects on numbers of red cells and quality of suspension fluid.

    Science.gov (United States)

    Read, M S; Coles, P; Pomeroy, M; Anderson, E; Aziz, M I

    2014-11-01

    We investigated the utility of a cell-saver device for processing out-of-date red blood cells, by washing twenty bags of red blood cells that had been stored for between 36 and 55 days. The volume of recovered cells, and the characteristics of the suspension fluid, were measured before and after treatment. The ratio of free haemoglobin to total haemoglobin was up to 0.02 before processing, and up to 0.011 afterwards, changing by between -0.013 and +0.003. This ratio met the current standard for free haemoglobin (less than 0.008 in more than 75% of samples), both before and after processing. Ninety-three percent of red blood cells survived the process. Potassium ion concentration fell from above 15 mmol.l(-1) in all cases, to a mean of 6.4 mmol.l(-1) (p blood cells remained intact after conditioning using a cell-saver, and the process lowered concentrations of potentially toxic solutes in the fluid in which they were suspended.

  1. Clofibrate Induces Heme Oxygenase 1 Expression through a PPARα-Independent Mechanism in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    2013-11-01

    Full Text Available Background and Aims: Clofibrate, an established PPARα ligand, has recently been shown to have anticancer activity yet its mechanisms of action remain to be characterized. This study examined the effect of clofibrate on heme oxygenase-1 (HO-1 gene expression in A2780 (human ovarian cancer and DU145 (human prostate cancer cells. Methods and Results: We demonstrate that clofibrate induces HO-1 expression in a concentration- and time-dependent manner. The induction of HO-1 by clofibrate was detected at both mRNA and protein levels and the HO-1 gene promoter activity was also dramatically induced by clofibrate, indicating that clofibrate up-regulates HO-1 gene transcription. Surprisingly, the induction of HO-1 by clofibrate was mediated by the Nrf2 signaling pathway, not by the PPARα pathway. This was primarily demonstrated by siRNA knockdown of Nrf2 expression that significantly attenuated clofibrate-induced HO-1 gene transcription, and siRNA knockdown of PPARα that had no effect on clofibrate-induced HO-1 promoter activity. Furthermore, deletion of the antioxidant response elements (AREs in the HO-1 gene promoter diminished clofibrate-induced HO-1 transcription and deletion of the PPAR response elements (PPREs had no such effect. Likewise, application of PPARα antagonists had no effect on clofibrate-induced HO-1 expression. Conclusion: Clofibrate induces HO-1 gene expression in cancer cells through a PPARα-independent mechanism and the Nrf2 signaling pathway is indispensible for this induction.

  2. A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis

    Science.gov (United States)

    Kollmann, Karoline; Heller, Gerwin; Schneckenleithner, Christine; Warsch, Wolfgang; Scheicher, Ruth; Ott, Rene G.; Schäfer, Markus; Fajmann, Sabine; Schlederer, Michaela; Schiefer, Ana-Iris; Reichart, Ursula; Mayerhofer, Matthias; Hoeller, Christoph; Zöchbauer-Müller, Sabine; Kerjaschki, Dontscho; Bock, Christoph; Kenner, Lukas; Hoefler, Gerald; Freissmuth, Michael; Green, Anthony R.; Moriggl, Richard; Busslinger, Meinrad; Malumbres, Marcos; Sexl, Veronika

    2013-01-01

    Summary In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6’s kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6’s central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a. PMID:23948297

  3. Investigation of low temperature solid oxide fuel cells for air-independent UUV applications

    Science.gov (United States)

    Moton, Jennie Mariko

    Unmanned underwater vehicles (UUVs) will benefit greatly from high energy density (> 500 Wh/L) power systems utilizing high-energy-density fuels and air-independent oxidizers. Current battery-based systems have limited energy densities (UUV energy densities, and the current study explores how SOFCs based on gadolinia-doped ceria (GDC) electrolytes with operating temperatures of 650°C and lower may operate in the unique environments of a promising UUV power plant. The plant would contain a H 2O2 decomposition reactor to supply humidified O2 to the SOFC cathode and exothermic aluminum/H2O combustor to provide heated humidified H2 fuel to the anode. To characterize low-temperature SOFC performance with these unique O2 and H2 source, SOFC button cells based on nickel/GDC (Gd0.1Ce0.9O 1.95) anodes, GDC electrolytes, and lanthanum strontium cobalt ferrite (La0.6Sr0.4Co0.2Fe0.8O3-δ or LSCF)/GDC cathodes were fabricated and tested for performance and stability with humidity on both the anode and the cathode. Cells were also tested with various reactant concentrations of H2 and O2 to simulate gas depletion down the channel of an SOFC stack. Results showed that anode performance depended primarily on fuel concentration and less on the concentration of the associated increase in product H2O. O 2 depletion with humidified cathode flows also caused significant loss in cell current density at a given voltage. With the humidified flows in either the anode or cathode, stability tests of the button cells at 650 °C showed stable voltage is maintained at low operating current (0.17 A/cm2) at up to 50 % by mole H2O, but at higher current densities (0.34 A/cm2), irreversible voltage degradation occurred at rates of 0.8-3.7 mV/hour depending on exposure time. From these button cell results, estimated average current densities over the length of a low-temperature SOFC stack were estimated and used to size a UUV power system based on Al/H 2O oxidation for fuel and H2O2 decomposition

  4. Analysis of blood transfusion predictors in patients undergoing elective oesophagectomy for cancer

    Directory of Open Access Journals (Sweden)

    Welch Neil T

    2008-01-01

    Full Text Available Abstract Background Oesophagectomy for cancers is a major operation with significant blood loss and usage. Concerns exist about the side effects of blood transfusion, cost and availability of donated blood. We are not aware of any previous study that has evaluated predictive factors for perioperative blood transfusion in patients undergoing elective oesophagectomy for cancer. This study aimed to audit the pattern of blood crossmatch and to evaluate factors predictive of transfusion requirements in oesophagectomy patients. Methods Data was collected from the database of all patients who underwent oesophagectomy for cancer over a 2-year period. Clinico-pathological data collected included patients demographics, clinical factors, tumour histopathological data, preoperative and discharge haemoglobin levels, total blood loss, number of units of blood crossmatched pre-, intra- and postoperatively, number of blood units transfused, crossmatched units reused for another patient and number of blood units wasted. Clinico-pathological variables were evaluated and logistic regression analysis was performed to determine which factors were predictive of blood transfusion. Results A total of 145 patients with a male to female ratio of 2.5:1 and median age of 68 (40–85 years were audited. The mean preoperative haemoglobin (Hb was 13.0 g/dl. 37% of males (Hb 70 years, Hb level Conclusion The cohort of patients audited was over-crossmatched. The identified independent predictors of blood transfusion should be considered in preoperative blood ordering for oesophagectomy patients. This study has directly led to a reduction in the maximum surgical blood-ordering schedule for oesophagectomy to 2 units and a reaudit is underway.

  5. Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

    International Nuclear Information System (INIS)

    random but is independent of the parental origin. The non-disease specific aberrant epigenetic profile displayed in peripheral blood cells of patients with a solid tumour (unlike genetic aberrations) can be reversed, by an epigenetic drug applied in vitro, to the normal. It appears that the cancerous status differentiates between two allelic counterparts in a non-random manner, but independent of the parental origin

  6. Transfusion practice in orthotopic liver transplantation

    Directory of Open Access Journals (Sweden)

    Devi Allanki

    2009-01-01

    Full Text Available Liver transplant procedures require the most blood components, despite the fact that blood use in liver transplantation has declined dramatically over the last decade. Liver transplant recipients present unique challenges, not only in terms of blood supply, but also requirements for specialized blood components, serologic problems, and immunologic effects of transfusion on both the allograft and the recipient. The cause of intraoperative blood loss in liver transplantation is multifactorial, due to both technical factors and poor coagulation control. This procedure carries the risk of massive blood loss, which requires massive transfusions and is associated with postoperative infections, reduced graft survival, multi-organ dysfunction, and higher risk of mortality. Efforts to reduce intraoperative bleeding leading to limitation of blood transfusions are desirable to improve results and also to control costs. Method of literature search: The name of topic is typed and searched in Google search.The name of topic is typed and searched in PubMed search. Related articles were also searched. Some standard books in Transfusion Medicine were also referred.

  7. Massive transfusion protocols: current best practice

    Directory of Open Access Journals (Sweden)

    Hsu YM

    2016-03-01

    Full Text Available Yen-Michael S Hsu,1 Thorsten Haas,2 Melissa M Cushing1 1Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA; 2Department of Anesthesia, University Children's Hospital Zurich, Zurich, Switzerland Abstract: Massive transfusion protocols (MTPs are established to provide rapid blood replacement in a setting of severe hemorrhage. Early optimal blood transfusion is essential to sustain organ perfusion and oxygenation. There are many variables to consider when establishing an MTP, and studies have prospectively evaluated different scenarios and patient populations to establish the best practices to attain improved patient outcomes. The establishment and utilization of an optimal MTP is challenging given the ever-changing patient status during resuscitation efforts. Much of the MTP literature comes from the trauma population, due to the fact that massive hemorrhage is the leading cause of preventable trauma-related death. As we come to further understand the positive and negative clinical impacts of transfusion-related factors, massive transfusion practice can be further refined. This article will first discuss specific MTPs targeting different patient populations and current relevant international guidelines. Then, we will examine a wide selection of therapeutic products to support MTPs, including newly available products and the most suitable of the traditional products. Lastly, we will discuss the best design for an MTP, including ratio-based MTPs and MTPs based on the use of point-of-care coagulation diagnostic tools. Keywords: hemorrhage, MTP, antifibrinolytics, coagulopathy, trauma, ratio, logistics, guidelines, hemostatic

  8. [Autologous transfusion in obstetrics and fetal safety].

    Science.gov (United States)

    Rech, F; Patella, A; Cecchi, A; Ippolito, M; Indraccolo, S R

    1994-06-01

    It is common knowledge that for modern medicine transfusion therapy represents a precious resource and an often mandatory option. It is equally known that autohemotransfusion (or autologous transfusion) provides further advantages: certainty of blood availability when necessary, absence of transfusion reactions, elimination of the risk of infections that is still associated with the traditional homologous transfusions. In its most widespread application, autotransfusion provides for the donation of one or more units of autologous blood, mostly before elective surgery. Even in obstetrics the practice of autologous blood donation with the aim of autotransfusion is finding increasing employment. However, there are still controversial aspects and the need is pointed out for more authoritative verifications as refers to the alleged innocuity to the fetus of acute maternal blood loss. The present study was performed to contribute personal experience to a better definition of the possible interactions between autologous blood donation during pregnancy and unborn child welfare. To this end, 80 term pregnant women underwent fetal heart rate electronic monitoring before, during and after the donation of one unit of autologous blood. Both during and after the phlebotomy there were no cardiotocographic signs of fetal hypo-oxygenation. Even the non stress tests performed at a distance of 24 hours and those that were periodically repeated afterwards were normal, confirming the safety of autologous predonation during pregnancy. However, the authors think that in obstetrics it is still premature to consider the experimental phase of autotransfusion as definitively exhausted. PMID:7936387

  9. [Transfusion of plasma: products-indications].

    Science.gov (United States)

    Djoudi, R

    2013-05-01

    The use of therapeutic plasma has increased in France by more than 40% since 2002. This growth may be explained by the improvement in transfusion safety, the diminution of the risk of transmission of pathogens and the regained confidence of the physicians in blood products. Therapeutic plasma also benefits from additional procedures to reduce infectious (securisation) or immunological risks (selection of blood donors). Its application in massive transfusions has undergone a significant evolution over the last few years. A proactive attitude favouring early and important use of plasma on the basis of pre-established protocols is advocated henceforth. The prescription of therapeutic plasma for other indications must be guided by the results of biological tests and an evaluation of the haemorrhagic risk. Despite regular updating of the guidelines for good transfusion practice, plasma is still sometimes prescribed for prophylactic purposes in situations where the biological and/or clinical criteria do not justify it. Moreover, it is not recommended to use fresh frozen plasma in cases of deficiency of coagulation factors if the specific concentrates are available as intravenous fluids. Complementary clinical studies will be necessary to evaluate, in certain indications, the real benefits of the transfusion of plasma and the interest of replacing it by concentrates of coagulant factors (fibrinogen, prothrombin complex).

  10. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney

    2006-07-01

    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  11. A Bar Code and Radio-Frequency Identification System for Transfusion Safety

    Institute of Scientific and Technical Information of China (English)

    Sandler SG; DiBandi L; Langeberg A; Gibble J; Wilson C; Feldman CF

    2006-01-01

    This presentation will describe a pilot study of radio-frequency (RF) identification tags ("chips") that was conducted in parallel with standard procedures for the collection and testing of Red Blood Cells (Greater Chesapeake and Potomac Region, American Red Cross Biomedical Services, Baltimore, MD) and transfusion (Georgetown University Hospital, Washington, DC). The purpose of the study was to evaluate whether multi-write RF chips could be attached to blood bags, programmed, and used to facilitate the collection of information from (1) a blood bag manufacturer to (2) a blood collection center and, subsequently, to (3) a hospital transfusion service.

  12. Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry

    DEFF Research Database (Denmark)

    Hagemo, Jostein S; Christiaans, Sarah C; Stanworth, Simon J;

    2015-01-01

    of massive transfusion (MT) using rotational thromboelastometry (ROTEM) assays. METHODS: In this prospective international multicentre cohort study, adult trauma patients who met the local criteria for full trauma team activation from four major trauma centres were included. Blood was collected on arrival...... to the emergency department and analyzed with laboratory international normalized ratio (INR), fibrinogen concentration and two ROTEM assays (EXTEM and FIBTEM). ATC was defined as laboratory INR >1.2. Transfusion requirements of ≥10 units of packed red blood cells within 24 hours were defined as MT. Performance...

  13. Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation and Anchorage-Independence in MDCK Cells.

    Directory of Open Access Journals (Sweden)

    Chia Chu

    Full Text Available The epithelial-mesenchymal transition (EMT is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage-dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5. The comparison identified several genes involved in the EMT process that were differentially expressed between the anchorage-dependent and the anchorage-independent MDCK cell lines. The hepatocyte growth factor gene (hgf was found to be over-expressed in the engineered MDCK-siat7e cells at both transcription and protein expression levels. Phosphorylation analysis of the MET receptor tyrosine kinase confirmed the activation of an autocrine loop of the HGF/ MET signaling pathway in the MDCK-siat7e cells. When MET activities were suppressed by using the small-molecular inhibitor drug PF-02341066 (Crizotinib, the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells. These observations indicate that the MET receptor plays a central role in the growth properties of the MDCK cells and its phosphorylation status is likely dependent on sialylation. Further investigation of the downstream signaling targets in the MET network showed that the degree of MDCK cell adhesion correlated with secretion levels of a matrix metalloproteinase, MMP1, suggesting a role of metalloproteinases in the EMT process. These results demonstrate that in addition to its application in biotechnology processes, MDCK-siat7e may serve as a model cell for metastasis studies to decipher the sequence of events leading up to the activation of EMT.

  14. Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation and Anchorage-Independence in MDCK Cells.

    Science.gov (United States)

    Chu, Chia; Bottaro, Donald P; Betenbaugh, Michael J; Shiloach, Joseph

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage-dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5). The comparison identified several genes involved in the EMT process that were differentially expressed between the anchorage-dependent and the anchorage-independent MDCK cell lines. The hepatocyte growth factor gene (hgf) was found to be over-expressed in the engineered MDCK-siat7e cells at both transcription and protein expression levels. Phosphorylation analysis of the MET receptor tyrosine kinase confirmed the activation of an autocrine loop of the HGF/ MET signaling pathway in the MDCK-siat7e cells. When MET activities were suppressed by using the small-molecular inhibitor drug PF-02341066 (Crizotinib), the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells. These observations indicate that the MET receptor plays a central role in the growth properties of the MDCK cells and its phosphorylation status is likely dependent on sialylation. Further investigation of the downstream signaling targets in the MET network showed that the degree of MDCK cell adhesion correlated with secretion levels of a matrix metalloproteinase, MMP1, suggesting a role of metalloproteinases in the EMT process. These results demonstrate that in addition to its application in biotechnology processes, MDCK-siat7e may serve as a model cell for metastasis studies to decipher the sequence of events leading up to the activation of EMT. PMID:26848584

  15. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.

    Directory of Open Access Journals (Sweden)

    Kees Meijer

    Full Text Available BACKGROUND: Obesity promotes inflammation in adipose tissue (AT and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA in obese state activate AT macrophages (ATM that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. METHODS AND RESULTS: Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. CONCLUSION: Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by

  16. The impact of electronic decision support on transfusion practice: a systematic review.

    Science.gov (United States)

    Hibbs, Stephen P; Nielsen, Nathan D; Brunskill, Susan; Doree, Carolyn; Yazer, Mark H; Kaufman, Richard M; Murphy, Michael F

    2015-01-01

    Decision support systems (DSSs) provide clinicians with tailored treatment recommendations by combining individual patient information and local guidelines. The objective of this systematic review was to assess the effects of electronic DSS on blood product ordering practices. Eligible studies were identified from searches of MEDLINE, Embase, CINAHL, The Cochrane Library, PubMed, and the Transfusion Evidence Library from January 2000 to April 2014. Of these, 23 articles were eligible, resulting in the inclusion of 20 independent studies in this systematic review. There was a significant variation in study population, the type of DSS used, and outcome reporting. All but one study used a before-after design without any element of randomization. Overall, there is good evidence that implementation of a DSS improves red blood cell usage. The effect of a DSS on plasma, platelets, and cryoprecipitate usage is less clear probably because fewer studies have been conducted focusing on these products. In addition, the introduction of a DSS resulted in cost savings in the 7 studies that reported financial outcomes. Patient outcomes were generally not studied in detail, and there were few data on the sustainability of the effect of DSS. Further data are needed to assess the effect of a DSS on blood products other than red blood cell, and future studies should standardize reporting of outcomes. PMID:25535095

  17. Use of an Immobilized Monoclonal Antibody to Examine Integrin &agr;5&bgr;1 Signaling Independent of Cell Spreading

    Directory of Open Access Journals (Sweden)

    Bao Wenjie

    2002-01-01

    Full Text Available Cell attachment to the extracellular matrix (ECM engages integrin signaling into the cell, but part of the signaling response also stem from cell spreading (3. To analyze specific integrin signaling-mediated responses independent of cell spreading, we developed a method engaging integrin signaling by use of an immobilized anti-integrin monoclonal antibody (mab directed against the fibronectin (FN receptor integrin &agr;5&bgr;1. ECV 304 cells were plated onto FN or immobilized mab JBS5 (anti-integrin &agr;5&bgr;1 or onto poly-L-lysin (P-L-L, which mediates integrin-independent attachment. Cells attached and spread on FN, while cells on JBS5 or P-L-L attached but did not spread. Importantly, plating onto FN or mab JBS5 gave rise to identical integrin-induced responses, including a down-regulation of the cyclin-dependent kinase (Cdk2 inhibitors p21CIP1 and p27KIP1, while attachment to P-L-L did not. We conclude that engagement of the FN-receptor integrin &agr;5&bgr;1 induces integrin signaling regulating the Cdk2-inhibitors independent of cell spreading and present a method for how integrin signaling can be analyzed separate from the effects of cell spreading.

  18. Acute Hemolytic Transfusion Reaction in a Patient with Bombay Phenotype: Implications for ABO Grouping.

    Science.gov (United States)

    Malhotra, Sheetal; Dhawan, Hari Krishan; Jain, Ashish; Sachdev, Suchet; Marwaha, Neelam

    2014-09-01

    Bombay blood group is a rare phenotype that is characterized serologically by absence of H, A and B antigens on red cell surface and presence of corresponding antibodies in the serum. We report a case of 45-year old patient having Bombay blood group phenotype who experienced an acute reaction due to transfusion of mismatched blood unit.

  19. Well being of obstetric patients on minimal blood transfusions (WOMB trial)

    NARCIS (Netherlands)

    B.W. Prick (Babette); E.A.P. Steegers (Eric); A.G. Jansen (Gerard); W.C.J. Hop (Wim); M.L.E. Essink-Bot (Marie-Louise); N.C.J. Peters; C.A. Uyl-de Groot (Carin); D.N.M. Papatsonis (Dimitri); B.M.C. Akerboom (Bettina); G.C.H. Metz (Godfried); H.A. Bremer (Henk); A.J. van Loon (Aren); R.H. Stigter (Rob); J.A.M. van der Post (Joris); M. van Alphen (Marcel); M. Porath (Martina); R.J.P. Rijnders (Robbert); M.E.A. Spaanderman; D.H. Schippers (Daniela); K.W.M. Bloemenkamp (Kitty); K.E. Boers (Kim); H.C.J. Scheepers; F.J.M.E. Roumen (Frans); A. Kwee (Anneke); N.W.E. Schuitemaker (Nico); B.W.J. Mol (Ben); D.J. van Rhenen (Dirk Jan); J.J. Duvekot (Johannes)

    2010-01-01

    textabstractBackground: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfu

  20. Rapid activation of Rac GTPase in living cells by force is independent of Src.

    Directory of Open Access Journals (Sweden)

    Yeh-Chuin Poh

    Full Text Available It is well known that mechanical forces are crucial in regulating functions of every tissue and organ in a human body. However, it remains unclear how mechanical forces are transduced into biochemical activities and biological responses at the cellular and molecular level. Using the magnetic twisting cytometry technique, we applied local mechanical stresses to living human airway smooth muscle cells with a magnetic bead bound to the cell surface via transmembrane adhesion molecule integrins. The temporal and spatial activation of Rac, a small guanosine triphosphatase, was quantified using a fluorescent resonance energy transfer (FRET method that measures changes in Rac activity in response to mechanical stresses by quantifying intensity ratios of ECFP (enhanced cyan fluorescent protein as a donor and YPet (a variant yellow fluorescent protein as an acceptor of the Rac biosensor. The applied stress induced rapid activation (less than 300 ms of Rac at the cell periphery. In contrast, platelet derived growth factor (PDGF induced Rac activation at a much later time (>30 sec. There was no stress-induced Rac activation when a mutant form of the Rac biosensor (RacN17 was transfected or when the magnetic bead was coated with transferrin or with poly-L-lysine. It is known that PDGF-induced Rac activation depends on Src activity. Surprisingly, pre-treatment of the cells with specific Src inhibitor PP1 or knocking-out Src gene had no effects on stress-induced Rac activation. In addition, eliminating lipid rafts through extraction of cholesterol from the plasma membrane did not prevent stress-induced Rac activation, suggesting a raft-independent mechanism in governing the Rac activation upon mechanical stimulation. Further evidence indicates that Rac activation by stress depends on the magnitudes of the applied stress and cytoskeletal integrity. Our results suggest that Rac activation by mechanical forces is rapid, direct and does not depend on Src

  1. Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Yukihiro Nishikawa

    Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

  2. Bar code technology improves positive patient identification and transfusion safety.

    Science.gov (United States)

    Sandler, S G; Langeberg, A; Dohnalek, L

    2005-01-01

    As a result of human error, an estimated 1 in 12,000 blood transfusions is given to the wrong patient. The cause of nearly all of these errors is failure of hospital personnel to identify positively intended transfusion recipients, their blood samples for cross-matching, or their correct blood components. We describe our experience using a point-of-care bar code transfusion safety system that links patients' bar-coded wristbands, with bar-coded labels on blood sample tubes, blood component bags, and nurses' identification badges. The result was 100 % accuracy of matching patients, their blood samples, and components for transfusions. For verifying information before starting blood transfusions, nurses preferred bar code "double checks" to conventional visual "double checks" by a second nurse. Methods are needed to reinforce nurses' proficiency with technological approaches to transfusion safety, such as software-driven bar code scanning, in situations where transfusions are administered infrequently. PMID:16050151

  3. The new Scandinavian Donations and Transfusions database (SCANDAT2)

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Rostgaard, Klaus; Vasan, Senthil K;

    2015-01-01

    AND METHODS: We have previously created the anonymized Scandinavian Donations and Transfusions (SCANDAT) database, containing data on blood donors, blood transfusions, and transfused patients, with complete follow-up of donors and patients for a range of health outcomes. Here we describe the re...... registers to attain complete follow-up for up to 47 years regarding hospital care, cancer, and death. RESULTS: After removal of erroneous records, the database contained 25,523,334 donation records, 21,318,794 transfusion records, and 3,692,653 unique persons with valid identification, presently followed......: It is possible to create a binational, nationwide database with almost 50 years of follow-up of blood donors and transfused patients for a range of health outcomes. We aim to use this database for further studies of donor health, transfusion-associated risks, and transfusion-transmitted disease....

  4. LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.

    Directory of Open Access Journals (Sweden)

    Roberta Bertelli

    Full Text Available Immunosuppressive regulatory T cells (Tregs have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna and/or drug induced (Adriamycin nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2 were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻ and irrespective of treatment (IL-2, IL-2/anti-IL-2, LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions.

  5. Possible configurations for an air independent propulsion (AIP) system for submarines based on fuel cells

    International Nuclear Information System (INIS)

    'Full text:' Conventional submarines employ an electric propulsion system, based on energy storage in batteries which are recharged using diesel motors connected to generator alternators. This limits their autonomy underwater given that it will be depend on the amount of energy that can be stored in the batteries; currently, a normal value is to have energy to navigate for three days at low speed. As of from the WWII, several shipyards began to carry out research on propulsion systems for submarines that would be capable of operating under anaerobic conditions, independent of the air (AIP Systems). Since then, several proposals have been considered, but there is one option that several navies are currently putting their trust in: fuel cells. The objective of this Project is to stress the different configurations that can be considered to this end, as regards the transportation of hydrogen and oxygen. From the hydrogen point of view, the possibilities of transporting it in metal hydrides or its on-board production through the reforming of different fuels (gas-oil, ethanol, methanol), are analyzed. This study also compares auxiliary systems (including CO2 removers), and proposes solutions, some of which are under development, indicating which are currently being considered to a greater extent. (author)

  6. Cell Length Independent PBRB Model for Simulations of HE Reaction Initiation, Growth, and Detonation

    Science.gov (United States)

    Dwivedi, Sunil

    2015-06-01

    It has been our focus to use the Physics Based Reaction Burn (PBRB) model to simulate reaction initiation, growth, and detonation of HE composites at the mesoscale. The idealization of hot spots as planar surfaces reduces the 3D model to a 1D hot spot cell (1DHSC) model. The idealization also renders the model dependent on the 1DHSC length and mesh size. New developments are presented making the PBRB model 1DHSC length independent. First, the accurate prediction of the gas-solid interface temperature and thermal gradient are essential, achieved through a finite difference scheme with 500-2000 thermal grid points. Second, keeping the burn mass constant while varying the 1DHSC length is essential, achieved by varying the hot spot specific surface area. 1D and 2D simulation results are presented for shock response of RDX at 1 km/s and 2 km/s impact velocities. The 5, 10, and 50 micro meters 1DHSC lengths yield near identical run-to-detonation, time-to-detonation, and detonation velocity in agreement with experimental data. It is concluded that the new developments make the PBRB model well suited as a generic EOS model for HE composites. - Dr. John Brennan, ARL is acknowledged for his interactions and support. This work is supported in part by ARL Grant W911NF-12-2-0053 and DTRA Grant HDTRA1-12-1-0004.

  7. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Liliana, E-mail: lilianam87@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Araújo, Isabel, E-mail: isa.araujo013@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Costa, Tito, E-mail: tito.fmup16@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Correia-Branco, Ana, E-mail: ana.clmc.branco@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Faria, Ana, E-mail: anafaria@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Chemistry Investigation Centre (CIQ), Faculty of Sciences of University of Porto, Rua Campo Alegre, 4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences of University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Martel, Fátima, E-mail: fmartel@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Keating, Elisa, E-mail: keating@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal)

    2013-07-15

    In this study we characterized {sup 3}H-2-deoxy-D-glucose ({sup 3}H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon {sup 3}H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells {sup 3}H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (V{sub max}) and affinity (K{sub m}), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that {sup 3}H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited {sup 3}H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4 h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. -- Highlights: • Glucose uptake by MCF7 and MDA-MB-231 cells is mainly mediated by GLUT1. • QUE and EGCG inhibit cellular glucose uptake thus abolishing the Warburg effect. • This process induces cytotoxicity and proliferation arrest in MCF7 cells. • The flavonoids’ effects are independent of estrogen receptor signalling.

  8. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells.

    Science.gov (United States)

    Kattan, Zilal; Minig, Vanessa; Leroy, Pierre; Dauça, Michel; Becuwe, Philippe

    2008-03-01

    Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer cells, i.e., MDA-MB231 and SKBR3 cells. We show that estrogen-independent cells expressed a significantly higher basal MnSOD level compared to estrogen-dependent human breast cancer cell lines (MCF-7 and T47D). For MDA-MB231 cells, the high-MnSOD level was accompanied by an overproduction of intracellular hydrogen peroxide (H2O2) and by a low expression of the major H2O2-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H2O2 content and caused a stimulation of growth with a reduced cell doubling time but induced a decrease of colony formation. Furthermore, treatment of MDA-MB231 cells with H2O2 scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H2O2 scavengers reduced the invasive properties of MDA-MB231 cells up to 43%, with a concomitant decrease of metalloproteinase-9 activity. We conclude that MnSOD plays a role in regulating tumor cell growth and invasive properties of estrogen-independent metastatic breast cancer cells. These action are mediated by MnSOD-dependent H2O2 production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.

  9. Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

    Science.gov (United States)

    Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

    2016-01-01

    In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

  10. Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner

    Energy Technology Data Exchange (ETDEWEB)

    Takegahara, Yuki; Yamanouchi, Keitaro, E-mail: akeita@mail.ecc.u-tokyo.ac.jp; Nakamura, Katsuyuki; Nakano, Shin-ichi; Nishihara, Masugi

    2014-05-15

    Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis. For this purpose, skeletal muscle progenitor cells were transfected with siRNA of PPARγ (siPPARγ) in an attempt to inhibit adipogenesis. Myosin heavy chain (MHC)-positive myotube formation was promoted in cells transfected with siPPARγ compared to that of cells transfected with control siRNA. To determine whether direct cell-to-cell contact between adipocytes and myoblasts is a prerequisite for adipocytes to affect myogenesis, skeletal muscle progenitor cells were cocultured with pre- or mature adipocytes in a Transwell coculture system. MHC-positive myotube formation was inhibited when skeletal muscle progenitor cells were cocultured with mature adipocytes, but was promoted when they were cocultured with preadipocytes. Similar effects were observed when pre- or mature adipocyte-conditioned medium was used. These results indicate that preadipocytes play an important role in maintaining skeletal muscle mass by promoting myogenesis; once differentiated, the resulting mature adipocytes negatively affect myogenesis, leading to the muscle deterioration observed in skeletal muscle pathologies. - Highlights: • We examined the effects of pre- and mature adipocytes on myogenesis in vitro. • Preadipocytes and mature adipocytes affect myoblast fusion. • Preadipocytes play an important role in maintaining skeletal muscle mass. • Mature adipocytes lead to muscle deterioration observed in skeletal muscle pathologies.

  11. Phosphoproteome analysis demonstrates the potential role of THRAP3 phosphorylation in androgen-independent prostate cancer cell growth.

    Science.gov (United States)

    Ino, Yoko; Arakawa, Noriaki; Ishiguro, Hitoshi; Uemura, Hiroji; Kubota, Yoshinobu; Hirano, Hisashi; Toda, Tosifusa

    2016-04-01

    Elucidating the androgen-independent growth mechanism is critical for developing effective treatment strategies to combat androgen-independent prostate cancer. We performed a comparative phosphoproteome analysis using a prostate cancer cell line, LNCaP, and an LNCaP-derived androgen-independent cell line, LNCaP-AI, to identify phosphoproteins involved in this mechanism. We performed quantitative comparisons of the phosphopeptide levels in tryptic digests of protein extracts from these cell lines using MS. We found that the levels of 69 phosphopeptides in 66 proteins significantly differed between LNCaP and LNCaP-AI. In particular, we focused on thyroid hormone receptor associated protein 3 (THRAP3), which is a known transcriptional coactivator of the androgen receptor. The phosphorylation level of THRAP3 was significantly lower at S248 and S253 in LNCaP-AI cells. Furthermore, pull-down assays showed that 32 proteins uniquely bound to the nonphosphorylatable mutant form of THRAP3, whereas 31 other proteins uniquely bound to the phosphorylation-mimic form. Many of the differentially interacting proteins were identified as being involved with RNA splicing and processing. These results suggest that the phosphorylation state of THRAP3 at S248 and S253 might be involved in the mechanism of androgen-independent prostate cancer cell growth by changing the interaction partners.

  12. The effect of large amount of suspended red blood cell transfusion on blood coagulation function in patients with surgery%大量输注悬浮红细胞对手术患者凝血功能的影响

    Institute of Scientific and Technical Information of China (English)

    郭鹏豪; 杨小立

    2016-01-01

    Objective To analyze the effects of large amount of suspended red blood cell transfusion and different injection rates between fresh plasma (FP) and red blood cell on blood coagulation function in patients with surgery. Methods 85 massive transfusion surgical patients from January 2014 to December 2015 in the fifth people''s hospital of Dongguan city were divided into observation group and control group according to the amount of suspended red blood cell transfusion. According to the ratios of plasma and suspended red blood cell transfusion, the patients were divided into high ratio group (≥1∶ 1),middle ratio group (1∶1-1∶2) and low ratio group (≤1∶2). Collecting venous blood, the hemoglobin (HGB), hematocrit (HCT) and coagulation related indicators’ changes of the before and after blood transfusion were compared. The coagulation related indicators contained platelet (PLT), fibrinogen (FIB), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT). ResultsAfter blood transfusion of all the patients, the HGB and HCT levels were significantly increased, and the PT, TT and APTT values were dramatically prolonged. The PLT and FIB of the observation group were significantly decreased, the differences were statistically significant (allP<0.05). In the middle and low ratio group, the PLT and FIB levels were significantly decreased, while the PT, TT and APTT values were dramatically prolonged. The levels’ changes of the low ratio group were more apparent. All the differences were statistically significant (allP<0.05). Conclusion Large amount of suspended red blood cell transfusion could lead to coagulation dysfunction in surgical patients. Increasing the ratios of plasma and suspended red blood cell transfusion could relieve the coagulation dysfunction.%目的:分析大量输注悬浮红细胞以及新鲜血浆与红细胞不同输注比例对手术患者凝血功能的影响。方法选择东莞市第五人民医院2014

  13. A simple clinical model for planning transfusion quantities in heart surgery

    Directory of Open Access Journals (Sweden)

    Biagioli Bonizella

    2011-06-01

    Full Text Available Abstract Background Patients undergoing heart surgery continue to be the largest demand on blood transfusions. The need for transfusion is based on the risk of complications due to poor cell oxygenation, however large transfusions are associated with increased morbidity and risk of mortality in heart surgery patients. The aim of this study was to identify preoperative and intraoperative risk factors for transfusion and create a reliable model for planning transfusion quantities in heart surgery procedures. Methods We performed an observational study on 3315 consecutive patients who underwent cardiac surgery between January 2000 and December 2007. To estimate the number of packs of red blood cells (PRBC transfused during heart surgery, we developed a multivariate regression model with discrete coefficients by selecting dummy variables as regressors in a stepwise manner. Model performance was assessed statistically by splitting cases into training and testing sets of the same size, and clinically by investigating the clinical course details of about one quarter of the patients in whom the difference between model estimates and actual number of PRBC transfused was higher than the root mean squared error. Results Ten preoperative and intraoperative dichotomous variables were entered in the model. Approximating the regression coefficients to the nearest half unit, each dummy regressor equal to one gave a number of half PRBC. The model assigned 4 units for kidney failure requiring preoperative dialysis, 2.5 units for cardiogenic shock, 2 units for minimum hematocrit at cardiopulmonary bypass less than or equal to 20%, 1.5 units for emergency operation, 1 unit for preoperative hematocrit less than or equal to 40%, cardiopulmonary bypass time greater than 130 minutes and type of surgery different from isolated artery bypass grafting, and 0.5 units for urgent operation, age over 70 years and systemic arterial hypertension. Conclusions The regression

  14. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

    Directory of Open Access Journals (Sweden)

    Jessberger Sebastian

    2006-11-01

    Full Text Available Abstract Background In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. Results We found that (1 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2 the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3 positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. Conclusion These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

  15. Requirements of transcription factor Smad-dependent and -independent TGF-β signaling to control discrete T-cell functions

    OpenAIRE

    Gu, Ai-di; Wang, Yunqi; Lin, Lin; Zhang, Song S.; Wan, Yisong Y.

    2012-01-01

    TGF-β modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-β achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-β signaling for T-cell function. Smad2 and Smad3 double deficiency in T cells led to lethal inflammatory disorder in mice. Non-Treg cells were spontaneously acti...

  16. Circulating microRNAs as biomarkers for detection of autologous blood transfusion.

    Directory of Open Access Journals (Sweden)

    Nicolas Leuenberger

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion.

  17. Modification of fresh-frozen plasma transfusion practices through educational intervention.

    Science.gov (United States)

    Barnette, R E; Fish, D J; Eisenstaedt, R S

    1990-01-01

    The effect of an educational program designed to address misconceptions about the perioperative transfusion of fresh-frozen plasma (FFP) was examined. Results of a baseline audit of FFP use were compared to those of a study subsequent to the educational process. Statistical analysis of the data revealed that the decrease in the number of patients transfused with FFP, from 32 of 2077 operative cases in Group A (baseline) to 18 of 2540 operative cases in Group B (after education), was significant (p less than 0.01). Analysis of the justifications given for transfusion of FFP revealed that the increase in acceptable indications from 47 percent in Group A to 78 percent in Group B was also significant (p less than 0.05). There was no significant difference between the two groups in units of FFP transfused per patient (Group A, 3.66 +/- 3.2, vs. Group B, 2.47 +/- 1.7) or red cells (Group A, 2.84 +/- 5.2, vs. Group B, 5.22 +/- 4.4), and the patterns of platelet transfusion were similar in the two groups. There was a significant difference in the postoperative partial thromboplastin time (Group A, 38.2 +/- 8.7 vs. Group B, 56.3 +/- 24 seconds, p less than 0.01) but no significant difference in postoperative prothrombin time (Group A, 14.1 +/- 2.6 vs. Group B, 15.4 +/- 3.3 seconds). It can be concluded that an educational program designed to address misconceptions in transfusion practice can alter physician performance and thereby reduce the inappropriate use of FFP.

  18. Blood transfusion: patient identification and empowerment.

    Science.gov (United States)

    Stout, Lynn; Joseph, Sundari

    Positive patient identification is pivotal to several steps of the transfusion process; it is integral to ensuring that the correct blood is given to the correct patient. If patient misidentification occurs, this has potentially fatal consequences for patients. Historically patient involvement in healthcare has focused on clinical decision making, where the patient, having been provided with medical information, is encouraged to become involved in the decisions related to their individualised treatment. This article explores the aspects of patient contribution to patient safety relating to positive patient identification in transfusion. When involving patients in their care, however, clinicians must recognise the diversity of patients and the capacity of the patient to be involved. It must not be assumed that all patients will be willing or indeed able to participate. Additionally, clinicians' attitudes to patient involvement in patient safety can determine whether cultural change is successful.

  19. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus;

    2016-01-01

    Background: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health...... excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. Results: Among included patients, 2.......9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy...

  20. Identification of RHCE and KEL alleles in large cohorts of Afro-Caribbean and Comorian donors by multiplex SNaPshot and fragment assays: a transfusion support for sickle cell disease patients

    OpenAIRE

    2011-01-01

    Abstract To lower the alloimmunization risk following transfusion in blacks, we developed two genotyping assays for large-scale screening of Comorian and Afro-Caribbean donors. One was a multiplex SNaPshot assay designed to identify ces(340), ceMO/AR/EK/BI/SM, ces, ces(1006) and KEL*6/*7 alleles. The other was a multiplex fragment assay designed to detect RHD, RHD?and RHCE*C and 455A>C transversion consistent with (C)ces Type 1 and DIII Type5 ces. Variant RHCE*ce alleles or ...

  1. Bone Marrow Engraftment Analysis after Granulocyte Transfusion

    OpenAIRE

    Swierczynski, Sharon L.; Hafez, Michael J.; Philips, Juliet; Higman, Meghan A.; Berg, Karin D.; Murphy, Kathleen M.

    2005-01-01

    We present the case of a 6-year-old male who received an allogeneic bone marrow transplant as part of treatment for acute lymphoblastic leukemia. The patient relapsed 5 months after transplantation and received additional chemotherapy. He acquired an angioinvasive fungal infection that required transfusion of granulocytes. Approximately 5 weeks after relapsing (181 days after transplant), a bone marrow specimen was taken for molecular engraftment analysis and flow cytometry to assess graft lo...

  2. Twin-to-Twin Transfusion Syndrome

    OpenAIRE

    Muhammad Rusda; R. Haryono Roeshadi

    2009-01-01

    Twin-to-twin transfusion syndrome (TTTS), umumnya terjadi pada kehamilan kembar monochorion (MC), dimana terjadi donasi darah secara terus menerus dari satu janin ke janin yang lainnya (satu janin bertindak sebagai donor sedangkan janin yang lainnya bertindak sebagai resipien).Kehamilan kembar monokhorion sangat beresiko untuk mendapat berbagai jenis komplikasi, diantaranya: TTTS, pertumbuhan janin terhambat, kematian janin dan persalinan prematur. Mayoritas dari beberapa kompl...

  3. Paul Holland: contributions to transfusion medicine.

    Science.gov (United States)

    McCarthy, Leo J

    2013-07-01

    Paul Holland began his career in transfusion medicine in 1963 as an assistant to Dr. Paul Schmidt in the Blood Bank at the National Institutes of Health (NIH). He served at the NIH for 20 years and retired in 1983 with the rank of Captain in the Public Health Service. He subsequently became the Medical Director/CEO of the Sacramento Medical Foundation Blood Center, now Blood Source, a position he held for the next 21 years. Paul Holland has authored/co-authored 265 articles, chapters and monographs, mostly concerning issues relating to either viral hepatitis or HIV. In addition to his research career, Paul was a very active educator, having contributed importantly to the development of many current thought leaders in transfusion medicine. His distinguished career also included important administrative roles in national and international organizations relevant to transfusion medicine. He also was the recipient of many honors and awards which has won him wide-spread renown and the respect of his many colleagues.

  4. Successful implementation of strategies to transform Emergency Department transfusion practice.

    Science.gov (United States)

    Reed, Matthew J; Kelly, Sarah-Louise; Beckwith, Hannah; Innes, Catherine J; Manson, Lynn

    2013-01-01

    Blood component transfusion is an important and lifesaving Emergency Department (ED) procedure. It is not however risk-free and careful consideration of its clinical benefit for each individual patient is therefore essential. In 2008, we audited the patterns of blood component usage in 2007 within our ED. This work revealed that whilst 3209 units of blood component were ordered only 39.5% were transfused, and 9.5% were unaccounted for. This was the first and only published detailed look at ED blood transfusion practices. We had to address our poor traceability (i.e. unaccounted for units), our high blood usage, and our ordering of units which were then not transfused as this can lead to wastage. Firstly, better links between the ED and the Scottish National Blood Transfusion Service (SNBTS) were established. A set of improvement measures were then implemented including better ED medical and nursing staff education, monthly traceability reports sent to the ED clinical management teams, the introduction of an ED transfusion guideline, moving our blood fridge into the resuscitation room, having a named ED transfusion consultant and ED transfusion link nurse, ED consultant representation on the Hospital Transfusion Group and finally increasing awareness of ED emergency transfusion with a rotational thromboelastometry (ROTEM) research programme. In 2012, we re-audited our practice looking at our blood component usage in 2011. There was a 64% reduction in blood component ordering (3209 vs. 1034 units), a 39% reduction in blood component transfusion (1131 vs. 687 units), a 68% increase in the proportion of ordered units that were transfused and a 96% reduction in unaccounted units (289 vs. 9 units) between 2007 and 2011. In attempting to cost the savings resulting from our changes we showed that SNBTS spent £306,437 less in 2011 compared to 2007 on handling and issuing ED transfusion requests. Our improvements are immediately generalizable across the UK and the potential

  5. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Pierre-Jean Lamy

    Full Text Available Human epididymis secretory protein 4 (HE4 is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2 gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC, following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients was 0.78 (95% confidence interval [CI], 0.738-0.821; z test P <0.0001. Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9 and 46.4 weeks (95% CI, 38.6 to 56.3, respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95 for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.

  6. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lamy, Pierre-Jean; Plassot, Carine; Pujol, Jean-Louis

    2015-01-01

    Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738-0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.

  7. Sarcopenia is an independent prognostic factor in male patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Nakamura, Nobuhiko; Hara, Takeshi; Shibata, Yuhei; Matsumoto, Takuro; Nakamura, Hiroshi; Ninomiya, Soranobu; Kito, Yusuke; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Shiraki, Makoto; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

    2015-12-01

    Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen between June 2004 and May 2014. Sarcopenia was measured by the analysis of CT images at the L3 level before treatment. The surface of muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the L3 skeletal muscle index (L3 SMI, cm(2)/m(2)). Median age at diagnosis in the 121 males and 86 females was 67 years (range, 19-86 years). The sex-specific cutoffs for the L3 SMI were determined by receiver operator curve (ROC) analysis. Sarcopenic patients were older than non-sarcopenic patients, with a median age of 70 and 65 years, respectively (p sarcopenic and non-sarcopenic patients. With a median follow-up of 50.4 months, the 3-year overall survival (OS) was 70 % in the sarcopenic group and 85 % in the non-sarcopenic group (p = 0.0260). In a subgroup analysis by gender, there was a significant difference in the OS when comparing sarcopenic and non-sarcopenic patients in males but not in females (p = 0.0003, p = 0.4440, respectively). Sarcopenia is an independent prognostic factor in male patients with DLBCL. PMID:26385388

  8. Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1

    DEFF Research Database (Denmark)

    Du, Dan; Pedersen, Esben; Wang, Zhipeng;

    2008-01-01

    -deficient immortalized and primary keratinocytes form only punctate primordial cell contacts in vitro, which cannot mature into belt-like junctions. This defect was independent of enhanced degradation of beta-catenin, but correlated to an impaired activation and localization of aPKCzeta in the Cdc42-null...

  9. Expression of Gli1 correlates with the transition of breast cancer cells to estrogen-independent growth.

    Science.gov (United States)

    Zhao, Jieying; Chen, Guangchun; Cao, Dongmei; Li, Yidong; Diao, Fei; Cai, Haoyu; Jin, Yiduo; Lu, Jian

    2010-01-01

    The failure of breast cancer treatment is largely due to the development of estrogen independence. Current data illustrate that Hedgehog (Hh) signaling may play an important role in breast cancer development. Here, we show that the expression of the Hh effector protein, Gli1 was significantly higher in estrogen-independent breast cancer cells than in estrogen-dependent cells. Our data showed for the first time that stable expression of Gli1 in ER positive breast cancer cell lines MCF-7 and T47D can induce estrogen-independent proliferation and promote G1/S phase transition, which associated with cyclin-Rb axi. Gli1 can also attenuate the response of proliferation to estrogenic stimulation, which was correlated with down-regulation of expression of ERalpha and PR, as well as down-regulation of transactivation of ERalpha. Our results suggest that up-regulation of Gli1 in breast cancer cells may be one of the mechanisms responsible for developing estrogen independence and this process may be regulated through down-regulation of expression and transactivation of ERalpha.

  10. Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Muhammad Khan

    2012-01-01

    Full Text Available Pseudolaric acid B (PLAB is one of the major bioactive components of Pseudolarix kaempferi. It has been reported to exhibit inhibitory effect on cell proliferation in several types of cancer cells. However, there is no report elucidating its effect on glioma cells and organ toxicity in vivo. In the present study, we found that PLAB inhibited growth of U87 glioblastoma cells in a dose-dependent manner with IC50~10 μM. Flow cytometry analysis showed that apoptotic cell death mediated by PLAB was accompanied with cell cycle arrest at G2/M phase. Using Western blot, we found that PLAB induced G2/M phase arrest by inhibiting tubulin polymerization in U87 cells. Apoptotic cell death was only partially inhibited by pancaspase inhibitor, z-VAD-fmk, which suggested that PLAB-induced apoptosis in U87 cells is partially caspase-independent. Further mechanistic study demonstrated that PLAB induced caspase-dependent apoptosis via upregulation of p53, increased level of proapoptotic protein Bax, decreased level of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose polymerase (PARP and caspase-independent apoptosis through apoptosis inducing factor (AIF. Furthermore, in vivo toxicity study demonstrated that PLAB did not induce significant structural and biochemical changes in mouse liver and kidneys at a dose of 25 mg/kg. Therefore, PLAB may become a potential lead compound for future development of antiglioma therapy.

  11. Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility

    Directory of Open Access Journals (Sweden)

    Serena Valsami

    2015-01-01

    Full Text Available Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization.

  12. Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility.

    Science.gov (United States)

    Valsami, Serena; Dimitroulis, Dimitrios; Gialeraki, Argyri; Chimonidou, Maria; Politou, Marianna

    2015-01-01

    Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility) have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA) antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT) count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization. PMID:26420927

  13. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bose Pinaki

    2012-08-01

    Full Text Available Abstract Background Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC. This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC using the quantitative fluorescence immunohistochemistry (IHC based AQUAnalysis technique. Methods Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Results Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS, with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006, in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses

  14. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique. Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent

  15. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.

    OpenAIRE

    Ohkura, Naganari; Hamaguchi, Masahide; Morikawa, Hiromasa; Sugimura, Kyoko; Tanaka, Atsushi; Ito, Yoshinaga; Osaki, Motonao; Tanaka, Yoshiaki; Yamashita, Riu; Nakano, Naoko; Huehn, Jochen; Fehling, Hans Joerg; Sparwasser, Tim; Nakai, Kenta; Sakaguchi, Shimon

    2012-01-01

    The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage. Here we showed that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of Treg cell-specific CpG hypomethylation pattern. Both events were induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation began in the thymus and c...

  16. [Platelet transfusion and immunization anti-Rh1: implication for immunoprophylaxis].

    Science.gov (United States)

    Chambost, H

    2014-11-01

    Rhesus (Rh) antigens are not expressed on platelets but residual red cells carry the risk of anti-D iso-immunization in transfusion recipients of platelet concentrates (PC). The main theoretical risk associated with this reaction relates to female subjects due to potential obstetrical situations of maternal-foetal Rh incompatibility. Isogroup PC transfusion in this system is therefore advised. However, logistical constraints impose frequent Rh-incompatible transfusions that require the recommendation of anti-Rh immunoglobulin in a girl of childbearing age in this situation. This recommendation, already restricted to a group of patients deserves to be questioned over a decade after being issued. Data from published reports are difficult to interpret because of the heterogeneity of the few series (CP type, immune status, timing of biological tests) but the current techniques for preparing products and most common use of CP apheresis limited the risk of immunization. Moreover, platelet transfusions are particularly relevant to immunocompromised populations which, to what extent (heavy chemotherapy and/or hematopoietic stem cells recipients) seems to be protected from this risk. It is noteworthy that the clinical consequences that may be expected from such immunization are not reported. Although some authors emphasize significant isoimmunization rates (maximum 19%), the heterogeneous conditions and the lack of evidence of clinical consequence suggest evaluating the recommendations or revising them towards more targeted indications of seroprophylaxis. PMID:25282489

  17. Cell proliferation potency is independent of FGF4 signaling in trophoblast stem cells derived from androgenetic embryos

    OpenAIRE

    Ogawa, Hidehiko; TAKYU, Ryuichi; MORIMOTO, Hiromu; TOEI, Shuntaro; SAKON, Hiroshi; GOTO, Shiori; MORIYA, SHOTA; Kono, Tomohiro

    2015-01-01

    We previously established trophoblast stem cells from mouse androgenetic embryos (AGTS cells). In this study, to further characterize AGTS cells, we compared cell proliferation activity between trophoblast stem (TS) cells and AGTS cells under fibroblast growth factor 4 (FGF4) signaling. TS cells continued to proliferate and maintained mitotic cell division in the presence of FGF4. After FGF4 deprivation, the cell proliferation stopped, the rate of M-phase cells decreased, and trophoblast gian...

  18. Feeder-independent continuous culture of the PICM-19 pig liver stem cell line

    Science.gov (United States)

    The PICM-19 pig liver stem cell line is a bipotent cell line, i.e., capable of forming either bile ductules or hepatocyte monolayers in vitro, that was derived from the primary culture of pig embryonic stem cells. The cell line has been strictly feeder-dependent in that cell replication morphology,...

  19. SLI-1 Cbl inhibits the engulfment of apoptotic cells in C. elegans through a ligase-independent function.

    Directory of Open Access Journals (Sweden)

    Courtney Anderson

    Full Text Available The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.

  20. Apical localisation of crumbs in the boundary cells of the Drosophila hindgut is independent of its canonical interaction partner stardust.

    Science.gov (United States)

    Kumichel, Alexandra; Knust, Elisabeth

    2014-01-01

    The transmembrane protein Crumbs/Crb is a key regulator of apico-basal epithelial cell polarity, both in Drosophila and in vertebrates. In most cases studied so far, the apical localisation of Drosophila Crumbs depends on the interaction of its C-terminal amino acids with the scaffolding protein Stardust. Consequently, embryos lacking either Crumbs or Stardust develop a very similar phenotype, characterised by the loss of epithelial tissue integrity and cell polarity in many epithelia. An exception is the hindgut, which is not affected by the loss of either gene. The hindgut is a single layered epithelial tube composed of two cell populations, the boundary cells and the principal cells. Here we show that Crumbs localisation in the principal cells depends on Stardust, similarly to other embryonic epithelia. In contrast, localisation of Crumbs in the boundary cells does not require Stardust and is independent of its PDZ domain- and FERM-domain binding motifs. In line with this, the considerable upregulation of Crumbs in boundary cells is not followed by a corresponding upregulation of its canonical binding partners. Our data are the first to suggest a mechanism controlling apical Crumbs localisation, which is independent of its conserved FERM- and PDZ-domain binding motifs.

  1. Apical localisation of crumbs in the boundary cells of the Drosophila hindgut is independent of its canonical interaction partner stardust.

    Directory of Open Access Journals (Sweden)

    Alexandra Kumichel

    Full Text Available The transmembrane protein Crumbs/Crb is a key regulator of apico-basal epithelial cell polarity, both in Drosophila and in vertebrates. In most cases studied so far, the apical localisation of Drosophila Crumbs depends on the interaction of its C-terminal amino acids with the scaffolding protein Stardust. Consequently, embryos lacking either Crumbs or Stardust develop a very similar phenotype, characterised by the loss of epithelial tissue integrity and cell polarity in many epithelia. An exception is the hindgut, which is not affected by the loss of either gene. The hindgut is a single layered epithelial tube composed of two cell populations, the boundary cells and the principal cells. Here we show that Crumbs localisation in the principal cells depends on Stardust, similarly to other embryonic epithelia. In contrast, localisation of Crumbs in the boundary cells does not require Stardust and is independent of its PDZ domain- and FERM-domain binding motifs. In line with this, the considerable upregulation of Crumbs in boundary cells is not followed by a corresponding upregulation of its canonical binding partners. Our data are the first to suggest a mechanism controlling apical Crumbs localisation, which is independent of its conserved FERM- and PDZ-domain binding motifs.

  2. Transfusion-transmitted infections: Existing and emerging pathogens

    Directory of Open Access Journals (Sweden)

    Kaur Paramjit

    2005-01-01

    Full Text Available In general, the risk of transfusion-transmitted infections has been greatly reduced today. However, blood-borne bacterial and parasitic infections and emerging infections transmitted through transfusion are an area of increasing concern. Implementation of stringent donor eligibility criteria, improved donor screening and more sophisticated as well as sensitive methods of antibody, antigen and viral genome detection, have virtually eliminated transfusion transmitted infection in developed countries. In developing countries like India, the risk of transfusion-transmitted infections is still considerable. A comprehensive MEDLINE search and review of relevant transfusion medicine literature were carried out and the data extracted and studied with particular reference to emerging pathogens transmitted through blood transfusion and posing a huge threat.

  3. Indications and Effects of Plasma Transfusions in Critically Ill Children

    DEFF Research Database (Denmark)

    Karam, Oliver; Demaret, Pierre; Shefler, Alison;

    2015-01-01

    critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS: During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary......RATIONALE: Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES: To...... identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. METHODS: Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All...

  4. Valuation of transfusion-free living in MDS: results of health utility interviews with patients

    Directory of Open Access Journals (Sweden)

    Lübbert Michael

    2009-09-01

    Full Text Available Abstract Background This study measured how myelodysplastic syndrome (MDS patients value transfusion independence (TI, reduced transfusions (RT and transfusion-dependence (TD using health utility assessment methodology. Methods 47 MDS patients were interviewed, US (n = 8, France (n = 9, Germany (n = 9 and the UK (n = 21, to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS and the Time Trade-Off (TTO method to value the health states on a 0 (dead to 1 (perfect health scale. Socio-demographic, clinical, and quality-of-life (EQ-5D characteristics were surveyed to describe the patient sample. Results and Discussion The mean age was 67 years (range: 29-83; 45% male, 70% retired; 40% had secondary/high school education, or higher (32%, and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23. Most patients (87% received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%, usual activities (40%, pain/discomfort (47%, and anxiety/depression (34%. Few patients had difficulty understanding the VAS (n = 3 and TTO (n = 4 exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p Conclusion Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.

  5. Uptake of fluorescent nano beads into BY2-cells involves clathrin-dependent and clathrin-independent endocytosis.

    Science.gov (United States)

    Bandmann, Vera; Müller, Jasmin Daniela; Köhler, Tim; Homann, Ulrike

    2012-10-19

    To follow endocytosis in BY-2 cells we made use of fluorescent nano beads. Beads with 20nm in diameter were internalised rapidly and accumulated partially in compartments also labelled by the endocytic marker FM4-64. Studies in BY-2 cells and protoplasts revealed that larger beads (100nm) were excluded from uptake into turgescent and plasmolysed cells while protoplasts were able to internalise beads with a diameter of up to 1000nm. Endocytosis of beads was only partially inhibited by the clathrin-specific inhibitor Ikarugamycin and strongly blocked by wortmannin. These results imply that uptake of beads involves clathrin-dependent and clathrin-independent endocytic mechanisms and supports the hypothesis that clathrin-independent endocytosis plays a general role in plants. PMID:23046971

  6. Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells

    OpenAIRE

    Hokaiwado, Naomi; Takeshita, Fumitaka; Naiki-Ito, Aya; Asamoto, Makoto; Ochiya, Takahiro; Shirai, Tomoyuki

    2008-01-01

    Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the ‘transgenic rat adenocarcinoma in prostate’ (TRAP) model, to analyze their gene expression using microarrays....

  7. Role of Subgroup Incompatibility in Newborn Jaundice Requiring Exchange Transfusion

    OpenAIRE

    Annagür, Ali; Altunhan, Hüseyin; Konak, Murat; Koç, Hasan; Örs, Rahmi

    2014-01-01

    We aimed to determine the role of exchange transfusion related complications, treatment, and etiology as well as subgroup incompatibility in patients subject to ET (exchange transfusion) due to newborn jaundice. 82 patients hospitalized due to newborn jaundice and exposed to exchange transfusion between August 2007 and August 2011 were retrospectively studied. Before ET mean total serum bilirubin was 29,2±9,83. The most frequent cause of ET was ABO incompatibility (31%) followed by...

  8. Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonist, independently of PPAR{gamma} in human glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Woo; Kim, Dae Seong; Kim, Hye Ryung; Kim, Hye Jin; Yang, Jin Mo; Ryu, Somi; Noh, Yoo Hun; Lee, Soo Hyun; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee [Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Koo, Hong Hoe, E-mail: hhkoo@skku.edu [Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Sung, Ki Woong, E-mail: kwsped@skku.edu [Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Greater than 30 {mu}M ciglitazone induces cell death in glioma cells. Black-Right-Pointing-Pointer Cell death by ciglitazone is independent of PPAR{gamma} in glioma cells. Black-Right-Pointing-Pointer CGZ induces cell death by the loss of MMP via decreased Akt. -- Abstract: Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPAR{gamma} in CGZ-induced cell death was examined. At concentrations of greater than 30 {mu}M, CGZ, a synthetic PPAR{gamma} agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 {mu}M CGZ effectively induced cell death after pretreatment with 30 {mu}M of the PPAR{gamma} antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPAR{gamma} was down-regulated cells by siRNA, lower concentrations of CGZ (<30 {mu}M) were sufficient to induce cell death, although higher concentrations of CGZ ( Greater-Than-Or-Slanted-Equal-To 30 {mu}M) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPAR{gamma}. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease i