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Sample records for viii inhibitor bypassing

  1. Acquired factor VIII inhibitor syndrome: A rare cause of hematuria

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    Muthuvel Seral Kannan

    2015-01-01

    Full Text Available A 50-year-old woman presented with gross hematuria for 1 month. Clinical examinations, laboratory investigations, ultrasound and contrast computed tomography were normal, except anemia. Cystoscopy revealed bloody efflux from the right side. Retrograde pyelogram showed filling defect in the renal pelvis and biopsy was inconclusive. Renal angiogram was normal. She developed ecchymosis on the right thigh and arm with elevated activated partial thromboplastin time. The partial thromboplastin time correction study and Bethesda study confirmed the presence of acquired factor VIII inhibitor (acquired hemophilia. With flexible ureterorenoscopy, the mass in the renal pelvis was removed and its histopathology revealed clotted blood. The patient was subsequently managed with steroids and Factor eight inhibitor bypass activity.

  2. Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

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    Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan

    2016-10-01

    Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

  3. Acquired Factor VIII Inhibitors: Three Cases

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    Tay Za Kyaw

    2013-03-01

    Full Text Available Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients’ ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.

  4. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

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    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  5. THE APPEARANCE OF THE INHIBITORS TO FACTOR VIII IN AN ELDER PATIENT WITH MILD HAEMOPHILIA A

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    Barbara Faganel

    2004-12-01

    Full Text Available Background. The inhibitors to F VIII are unusual in case of a mild haemophilia because the replacement therapy is seldom necessary. In case of severe trauma, when prolonged replacement therapy of F VIII is needed, the appearance of the inhibitors is more frequent. The mild form of the disease becomes a severe one and the haemorrhages are frequent.Patient and methods. In case of our patient with mild form of haemophilia, the inhibitors to F VIII developed after prolonged replacement therapy for treatement of subdural haemorrhage. In the article we describe recurrent haemorrhages and treatement of them with FEIBA and rF VIIa.Conclusions. Due to poor compliance of an elder patient we didn’t decide to treat the inhibitors for F VIII actively.

  6. The Staphylococcus aureus FASII bypass escape route from FASII inhibitors.

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    Morvan, Claire; Halpern, David; Kénanian, Gérald; Pathania, Amit; Anba-Mondoloni, Jamila; Lamberet, Gilles; Gruss, Alexandra; Gloux, Karine

    2017-10-01

    Antimicrobials targeting the fatty acid synthesis (FASII) pathway are being developed as alternative treatments for bacterial infections. Emergence of resistance to FASII inhibitors was mainly considered as a consequence of mutations in the FASII target genes. However, an alternative and efficient anti-FASII resistance strategy, called here FASII bypass, was uncovered. Bacteria that bypass FASII incorporate exogenous fatty acids in membrane lipids, and thus dispense with the need for FASII. This strategy is used by numerous Gram-positive low GC % bacteria, including streptococci, enterococci, and staphylococci. Some bacteria repress FASII genes once fatty acids are available, and "constitutively" shift to FASII bypass. Others, such as the major pathogen Staphylococcus aureus, can undergo high frequency mutations that favor FASII bypass. This capacity is particularly relevant during infection, as the host supplies the fatty acids needed for bacteria to bypass FASII and thus become resistant to FASII inhibitors. Screenings for anti-FASII resistance in the presence of exogenous fatty acids confirmed that FASII bypass confers anti-FASII resistance among clinical and veterinary isolates. Polymorphisms in S. aureus FASII initiation enzymes favor FASII bypass, possibly by increasing availability of acyl-carrier protein, a required intermediate. Here we review FASII bypass and consequences in light of proposed uses of anti-FASII to treat infections, with a focus on FASII bypass in S. aureus. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  7. Acquired factor VIII inhibitor (acquired hemophilia A) presenting as spontaneous blood-filled scrotum.

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    Verma, Rajanshu; Noack, Jill; Vemuri, Radhakrishna; Loehrke, Mark E

    2011-05-01

    Acquired hemophilia A, also known as acquired factor VIII deficiency, is an exceedingly rare bleeding diathesis that does not require any personal or family history of bleeding or clotting disorder. Because treatment is available, misdiagnosing or completely missing this diagnosis can be life threatening for patients. Clinicians should be aware that acquired forms of hemophilia do exist and are associated with high morbidity and mortality in elderly adults. We present a case of a 74-year-old man who was diagnosed with acquired factor VIII inhibitor during an admission for community-acquired pneumonia.

  8. A close insight to factor VIII inhibitor in the congenital hemophilia A.

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    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

    2016-09-01

    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  9. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A.

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    Goudemand, Jenny; Rothschild, Chantal; Demiguel, Virginie; Vinciguerrat, Christine; Lambert, Thierry; Chambost, Hervé; Borel-Derlon, Annie; Claeyssens, Ségolène; Laurian, Yves; Calvez, Thierry

    2006-01-01

    Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII). In addition to the usual end points (all inhibitors, high inhibitors), we also examined a third end point (high inhibitors and/or immune tolerance induction). The risk of inhibitor development was higher in patients treated with rFVIII than in patients treated with pFVIII, regardless of other risk factors (F8 genotype; nonwhite origin; history of inhibitors in patients with a family history of hemophilia; age at first FVIII infusion). The adjusted relative risk (RRa) for inhibitor development with rFVIII versus pFVIII was 2.4 (all inhibitors), 2.6 (high inhibitors), and 3.2 (high inhibitors and/or immune tolerance induction), respectively, depending on the end point (above). The pathophysiology of this large effect must be understood in order to improve the characteristics of recombinant products and to reduce the incidence of inhibitors to FVIII.

  10. Acquired hemophilia A caused by factor VIII inhibitors: report of a case.

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    Hosoya, Yoshinori; Matsumura, Miho; Madoiwa, Seiji; Zuiki, Toru; Matsumoto, Shiro; Nunomiya, Shin; Lefor, Alan; Sata, Naohiro; Yasuda, Yoshikazu

    2013-06-01

    We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.

  11. Treatment of radiation osteomyelitis of the mandible in a patient with acquired factor VIII inhibitor

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    Arimoto, Takamasa; Kishimoto, Hiromitsu; Matsumoto, Suwako; Kawanaka, Masao; Urabe, Masahiro; Yoshioka, Wataru [Hyogo Coll. of Medicine, Nishinomiya (Japan)

    1996-07-01

    A case of radiation osteomyelitis of mandible in a 56-year-old man with acquired factor VIII inhibitor is presented. He had undergone radiation therapy for malignant lymphoma of the tonsilar region seven years earlier, and also had received steroids to treat acquired factor VIII inhibitor for a year. On initial examination, he was given a diagnosis of phlegmon of the cheek caused by pericoronitis of the left lower wisdom tooth. To prevent the recurrence of inflammation, the wisdom tooth was extracted carefully, but radiation osteomyelitis occurred in association with a pathological fracture of the condylar head. After mini-pulse therapy with methylpredonisolone, segmental mandibulectomy and reconstruction with a titanium metal plate were performed. The postoperative course was satisfactory with no complications such as bleeding or infection. (author)

  12. Desenvolvimento de inibidores do fator VIII na hemofilia A Development of factor VIII inhibitors in hemophilia A

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    Daniel G. Chaves

    2009-01-01

    Full Text Available A hemofilia A é uma coagulopatia genética com herança recessiva ligada ao cromossomo X que afeta 1-2 a cada 10 mil indivíduos do sexo masculino nascidos vivos. Estes indivíduos têm baixas concentrações ou ausência do fator VIII (FVIII da coagulação no plasma e apresentam quadros hemorrágicos leves, moderados e graves, dependendo da atividade de FVIII circulante. Estes pacientes necessitam de constante reposição proteica e aproximadamente 30% deles desenvolvem aloanticorpos contra a proteína exógena. A síntese dos anticorpos anti-FVIII é iniciada quando o FVIII exógeno é endocitado por células apresentadoras de antígeno, degradado e apresentado às células T CD4+ na forma de peptídeos ligados a moléculas do complexo maior de histocompatibilidade (MHC de classe II. Alguns fatores de risco (paciente/tratamento podem ser relacionados ao desenvolvimento desta resposta imune. Neste contexto, as mutações no gene do FVIII e polimorfismos em genes envolvidos na resposta imune são candidatos moleculares como determinantes imunogenéticos na predisposição para o desenvolvimento de inibidores. Por não ser completamente entendido e controlado, o desenvolvimento desta resposta imune contra o FVIII constitui o maior problema decorrente do tratamento de indivíduos portadores de hemofilia A e faz-se necessária busca de opções que visem minimizar suas ações deletérias. Algumas alternativas de tratamento têm se mostrado eficazes no tratamento (anti-CD20, plasmaférese, concentrado de complexo protrombínico (PCCs, concentrado de complexo protrombínico ativado (APCCs, fator VII humano ativado, mas a retirada ou neutralização específica dos inibidores de FVIII ainda não foram alcançadas.Hemophilia A, which affects 1-2:10,000 live-born male neonates, is a genetic coagulopathy with recessive inheritance linked to the X chromosome. These individuals have low concentrations or no coagulation factor VIII (FVIII in the plasma

  13. Factor VIII genotype and inhibitor development in patients with haemophilia A: highest risk in patients with splice site mutations.

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    Boekhorst, J.; Lari, G.R.; D'Oiron, R.; Costa, J.M.; Novakova, I.R.O.; Ala, F.A.; Lavergne, J.M.; Heerde, W.L. van

    2008-01-01

    The appearance of inhibitory antibodies against factor VIII (FVIII) is the most severe and costly complication of replacement therapy in patients with haemophilia A (HA). To determine the relationship between FVIII genotype and inhibitor development, baseline FVIII activity, genotype and inhibitor

  14. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A.

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    Cannavò, Antonino; Valsecchi, Carla; Garagiola, Isabella; Palla, Roberta; Mannucci, Pier Mannuccio; Rosendaal, Frits R; Peyvandi, Flora

    2017-03-09

    The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors. © 2017 by The American Society of Hematology.

  15. Expanding the Ortholog Approach for Hemophilia Treatment Complicated by Factor VIII Inhibitors

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    Zakas, P.M.; Vanijcharoenkarn, K.; Markovitz, R.C.; Meeks, S.L.; Doering, C.B.

    2014-01-01

    Summary Background The formation of neutralizing antibodies (inhibitors) directed against human coagulation factor VIII (hFVIII) is a life-threatening pathogenic response that occurs in 20–30% of severe congenital hemophilia A patients and 0.00015% of remaining population (i.e. acquired hemophilia A). Interspecies amino acid sequence disparity among FVIII orthologs represents a promising strategy to mask FVIII from existing inhibitors while retaining procoagulant function. Evidence for the effectiveness of this approach exists in clinical data obtained for porcine FVIII products, which have demonstrated efficacy in the setting of congenital and acquired hemophilia. Objectives In the current study, recombinant (r) ovine FVIII (oFVIII), was evaluated for antigenicity and procoagulant activity in the context of human patient-derived and murine model-generated FVIII inhibitors. Methods The antigenicity of roFVIII was assessed using i) inhibitor patient plasma samples, ii) murine anti-FVIII MAbs, iii) immunized murine hemophilia A plasmas, and iv) an in vivo model of acquired hemophilia A Results Overall, roFVIII demonstrated reduced reactivity to, and inhibition by, anti-hFVIII immunoglobulin in patient plasmas. Additionally, several hFVIII epitopes were predicted and empirically shown not to exist within roFVIII. In a murine hemophilia A model designed to mimic clinical inhibitor formation, it was demonstrated that inhibitor titers to roFVIII were significantly reduced compared to the orthologous immunogens, rhFVIII or rpFVIII. Furthermore in a murine model of acquired hemophilia A, roFVIII administration conferred protection from bleeding following tail transection. Conclusion These data support the investigation of FVIII orthologs as treatment modalities in both the congenital and acquired FVIII inhibitor settings. PMID:25315236

  16. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011.

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    Collins, Peter W; Palmer, Benedict P; Chalmers, Elizabeth A; Hart, Daniel P; Liesner, Ri; Rangarajan, Savita; Talks, Katherine; Williams, Michael; Hay, Charles R M

    2014-11-27

    The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands. © 2014 by The American Society of Hematology.

  17. Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors.

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    Chai-Adisaksopha, Chatree; Nevitt, Sarah J; Simpson, Mindy L; Janbain, Maissaa; Konkle, Barbara A

    2017-09-25

    People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds. To assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors. We searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016. We included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors. Two authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria. We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.Two studies

  18. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

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    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...

  19. Incidence of low-titre factor VIII inhibitors in patients with haemophilia A: meta-analysis of observational studies.

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    Messori, A; Peyvandi, F; Mengato, D; Mannucci, P M

    2017-03-01

    A few studies have been focused on low-titre inhibitors in patients with haemophilia A. Although several putative factors have been implicated in the development of these inhibitors, solid data are still lacking. The aim of this study was to perform a proportion meta-analysis on the incidence of low-titre inhibitors in haemophilia A. We surveyed the PubMed database to identify studies on de novo development of low-titre inhibitors in haemophilia A patients. On the basis of these data, we carried out a proportion meta-analysis to summarize information on incidence and between-study variability. Furthermore, the following three covariates were assessed by meta-regression: (i) mild disease vs. severe haemophilia; (ii) status of previously untreated patient (PUP) as opposed to multi-transfused and (iii) type of factor VIII. Our literature search on PubMed extracted 340 eligible articles. From these, we selected 33 patient cohorts that were included in our meta-analysis (19 cohorts for PUPs and 14 cohorts for multi-transfused or unselected patients). The pooled incidence of low-titre inhibitors was 10.3% (95%CI: 8.3-12.5%) for studies including PUPs and 5.8% (95%CI: 2.5-10.4%) for the other studies; the difference was statistically significant (P = 0.003). Meta-regression of 31 patient cohorts found that mild disease and type of factor VIII were not associated with an increased incidence of low-titre inhibitors. Our results confirmed that PUPs show a higher incidence of low-titre inhibitors than the other patients. Furthermore, our data showed that mild haemophilia was not associated with an increased incidence of low-titre inhibitors. © 2017 John Wiley & Sons Ltd.

  20. Idiopathic factor VIII inhibitor autoantibody in a man presented after accident.

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    Mansouritorghabeh, H.; Lak, M.; Heerde, W.L. van

    2009-01-01

    Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of

  1. Endocytic receptor for pro-coagulant factor VIII: relevance to inhibitor formation.

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    Navarrete, Ana-Maria; Dasgupta, Suryasarathi; Teyssandier, Maud; Repesse, Yohann; Delignat, Sandrine; André, Sébastien; Bayry, Jagadeesh; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2010-12-01

    The immunogenicity of therapeutic factor VIII (FVIII) in patients with haemophilia A remains a critical issue in patient management. This review describes the immunological processes involved in the activation of the immune system against FVIII, with a particular focus on the role of endocytic receptors for the recognition of FVIII by antigen-presenting cells.

  2. Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: a comprehensive Argentine study of inhibitor risks.

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    Rossetti, L C; Szurkalo, I; Radic, C P; Abelleyro, M M; Primiani, L; Neme, D; Candela, M; Bianco, R P; de Tezanos Pinto, M; Larripa, I B; De Brasi, C D

    2013-07-01

    Inhibitor development against exogenous factor VIII is a severe impairment of replacement therapy affecting 18% of Argentine patients with severe haemophilia A (HA). To study the molecular predisposition for inhibitor development, we genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor-positive population (19 transients, 15 low responders, LR and 70 high responders, HR) of 104 severe-HA patients showed 59 Inv22 (intron 22 inversions), 18 small ins/del-frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2 domain secondary structure. In addition, a patient with mild HA and HR showed the missense p.Glu1704Lys associated with two neutral intronic substitutions potentially affecting the A3 domain. A case/control study (84/143) permitted estimation of F8 genotype-specific inhibitor risks [OR; prevalence (CI)] in severe-HA patients classifying a high-risk group including multi-exon deletions [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2; 21% (7-59)]; an average risk group including single-exon deletions, indel frameshifts and nonsense-HCh; and a low-risk group represented by missense defects [0.14; 3% (0.6-11)]. Analysis of inhibitor concordance/discordance in related patients indicated additional genetic factors other than F8 genotype for inhibitor formation. No significant inhibitor-predisposing factors related to FVIII product exposure were found in age- and F8 genotype-stratified populations of severe-HA patients. In conclusion, the Argentine HA patient series presents similar global and mutation-specific inhibitor risks than the HA database and other published series. This case-specific information will help in designing fitted therapies and follow-up protocols in Argentina. © 2013 John Wiley & Sons Ltd.

  3. Recombinant Factor VIIa (Eptacog Alfa): A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX

    OpenAIRE

    Katherine A. Lyseng-Williamson; Greg L. Plosker

    2007-01-01

    Recombinant factor VIIa (NovoSeven(R); also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of succe...

  4. Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis.

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    Haku, J; Nogami, K; Matsumoto, T; Ogiwara, K; Shima, M

    2014-01-01

    Assays to determine the optimal hemostatic effects of bypass therapy in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot waveform analysis (CWA), based on the continuous monitoring of routine coagulation parameters (prothrombin time/activated partial thromboplastin time), offers a useful method for assessing global clotting function. To investigate the technique of CWA for the hemostatic monitoring of bypass therapy in HA patients with inhibitors. Ellagic acid (Elg), tissue factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard parameters - clot time (CT), maximum coagulation velocity (|min1|), and acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a significant difference in these parameters between plasma from HA patients with inhibitors and normal plasmas; and (ii) a significant improvement in these indices in HA patients with inhibitors after bypass therapy. Experiments in vitro demonstrated that there were significant differences between plasma from HA patients with inhibitors and normal plasma with various triggers, in the order Elg > Elg/TF > TF. Addition of therapeutically achievable concentrations of bypassing agents, however, showed significant improvements in the different parameters only with Elg/TF, suggesting that this reagent provided the most appropriate assay. A total of 20 plasmas from HA patients with inhibitors in which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The postinfusion parameters CT and |min2| reflected clinical effects, and were close to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of perioperative hemostatic management of bypass therapy in HA patients with inhibitors. CWA is a promising method for the quantitative monitoring of bypass therapy during routine automated clotting assays with a modified trigger reagent comprising a well-balanced mixture of Elg and TF. © 2013 International Society on

  5. TREATMENT OF BLEEDING AND FACTOR VIII INHIBITORS IN ACQUIRED HEMOPHILIA A PATIENTS

    Directory of Open Access Journals (Sweden)

    Peter Černelč

    2004-12-01

    Full Text Available Background. Bleeding in acquired hemophilia A patients with FVIII autoantibodies is often severe. The authors describe a successfuly acquired hemophilia A treatment with Feiba, glucocorticoids and cyclophosphamide in three patients.Results. In a 66-year patient with chest hematoma and m. iliopsoas hematoma, APTT 50.1 s, FVIII 0.05 IU/mL and inhibitors FVIII (anti-FVIII 22 BU/ml were found. After treatment of hemorrhages with Feiba, dexamethasone and cyclophosphamide, FVIII increased to 0.54 IU/mL and no inhibitors were found on day seventeen. In a 46-year patient with advanced AIDS, multiple hematomas and liver cirrhosis after HCV infection, the platelet count was 92 × 109/L, APTT 48.2 s, FVIII 0.05 IU/mL and anti-FVIII 1.7 BU/mL. The hemorrhages were treated with FEIBA and methylprednisolone therapy was started after 14 months. After 42 days FVIII increased to 0.56 IU/mL and no inhibitors were found. In a 69-year patient suffering from thyroiditis and idiopathic thrombocytopenic purpura, extensive gluteal and chest hematomas were detected during the maintenance therapy with methylprednisolone 16 mg/day. The thrombocyte count was normal but APTT 48.8 s, FVIII 0.01 IU/mL and anti-FVIII 7.0 BU/mL was found. FVIII activity were 1.72 IU/mL and no inhibitors was noted after 330-days of treatment with cyclophosphamide.Conclusions. The treatment with FEIBA was effective in stopping the hemorrhages. The glucocorticoids were efficient in prompt decreasing of the inhibitor titer whereas the effect of cyclophosphamide was retarded.

  6. Successful immunoadsorption of life-threatening bleeding in factor VIII inhibitor disease, but no long-term remission with anti-CD20 treatment.

    Science.gov (United States)

    Grahammer, Florian; Fischer, Karl-Georg

    2015-08-30

    A 62-year-old man and a 64-year-old woman presented to our institution with acquired haemophilia A. They both developed life-threatening bleeding. Immunoadsorption using protein A columns was used to rapidly lower factor VIII inhibitor levels. Immunosuppression with steroids and the anti-CD20 antibody, rituximab, was instituted. Yet their effects were either partial or complicated by an early relapse. Repetitive cyclophosphamide administration led to a sustained immunological response. While immunoadsorption appears effective and safe to lower factor VIII inhibitor levels, it seems that further preferably randomised controlled trials are needed to establish the value of rituximab versus the standard immunosuppressive regime comprising cyclophosphamide. 2015 BMJ Publishing Group Ltd.

  7. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

    Full Text Available Development of inhibitory antibodies to coagulation factor VIII (fVIII is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa. However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I" kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II" inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined fVIII

  8. Global clotting assays - monitoring the effect of by-passing agents in haemophilia patients with inhibitors

    Directory of Open Access Journals (Sweden)

    Șerban Margit

    2017-04-01

    Full Text Available The development of FVIII/FIX inhibitor alloantibodies represents a severe complication requiring specific laboratory evaluation for establishing a life-saving therapy regimen. Our preliminary study aimed at elaborating a laboratory strategy for monitoring the effectiveness of Activated Prothrombin Complex Concentrate (APCC and recombinant activated factor VII (rFVIIa in haemophiliacs with inhibitors, by checking the reliability and clinical value of three complementary assays: clotting-time based coagulometry, thrombelastography (TEG and thrombin generation assay (TGA. The investigations were performed on 7 patients with severe haemophilia A with high titer inhibitors treated for 12 episodes of severe bleedings, 5 of them for surgical interventions. After the administration of bypassing agents (BPAs the clotting-time based assay brought changes only on prothrombin (p<0.01, potentially signaling a thrombotic risk, without any impact on the global hemostasis. TEG displayed prompt significant improvement only after rFVIIa (90μg/kg. TGA revealed significantly improved values for peak and velocity index, time to peak and start tail after both BPAs. Despite some disparities between biological hemostatic phenotype and clinical response to therapy, we concluded that TEG and TGA are the only current exploratory assays, expressing the quality of haemostatic control, representing a real support for a personalized, adapted therapy in hemophilia with inhibitors.

  9. Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients.

    Science.gov (United States)

    Pinto, P; Ghosh, K; Shetty, S

    2012-09-01

    Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI: 1.402-8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and 'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients. © 2012 Blackwell Publishing Ltd.

  10. Long-lasting remission and successful treatment of acquired factor VIII inhibitors using cyclophosphamide in a patient with systemic lupus erythematosus.

    Science.gov (United States)

    Trotta, F; Bajocchi, G; La Corte, R; Moratelli, S; Sun, L Y

    1999-10-01

    Acquired deficiency of clotting factor VIII (FVIII) is a rare bleeding diathesis seldom encountered in systemic lupus erythematosus (SLE). Reduction of FVIII activity by autoantibodies can cause potentially life-threatening situations. Herein, an SLE patient with a positive lupus anticoagulant (LAC) test who abruptly developed metrorrhagia 4 yr after diagnosis is reported. Coagulation tests revealed FVIII activity reduced to 3% and a prolonged aPTT. FVIII inhibitor(s) were found to be as high as 3.0 Bethesda Units. Plasmapheresis, immunoglobulins, prednisolone and FVIII plasma concentrates induced the cessation of metrorrhagia, but the clotting tests were barely improved. One month later, extensive ecchymosis appeared and worsened, despite re-administration of the previous therapy. Pulse cyclophosphamide followed by oral administration was then started with normalization of coagulation parameters and long-lasting disease remission.

  11. Drug Driven Synthetic Lethality: bypassing tumor cell genetics with a combination of Dbait and PARP inhibitors

    Science.gov (United States)

    Jdey, Wael; Thierry, Sylvain; Russo, Christophe; Devun, Flavien; Abo, Muthana Al; Noguiez-Hellin, Patricia; Sun, Jian-Sheng; Barillot, Emmanuel; Zinovyev, Andrei; Kuperstein, Inna; Pommier, Yves; Dutreix, Marie

    2016-01-01

    Purpose Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are Poly(ADP-Ribose) Polymerase (PARP) inhibitors (PARPi), which trigger synthetic lethality in tumors with Homologous Recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and Non Homologous End Joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy. Experimental design We characterized the DNA repair inhibition activity of PARPi (olaparib) and AsiDNA by monitoring repair foci formation and DNA damage. We analyzed the cell survival to standalone and combined treatments of 21 tumor cells, and 3 non-tumor cells. In 12 Breast Cancer (BC) cell lines, correlation with sensitivity to each drug and transcriptome were statistically analyzed to identify resistance pathways. Results Molecular analyses demonstrate that olaparib and AsiDNA respectively prevent recruitment of XRCC1 and RAD51/53BP1 repair enzymes to damage sites. Combination of both drugs increases the accumulation of unrepaired damage resulting in an increase of cell death in all tumor cells. In contrast, non-tumor cells do not show an increase of DNA damage nor lethality. Analysis of multi-level omics data from BC cells highlighted different DNA repair and cell cycle molecular profiles associated with resistance to AsiDNA or olaparib, rationalizing combined treatment. Treatment synergy was also confirmed with 6 other PARPi in development. Conclusion Our results highlight the therapeutic interest of combining AsiDNA and PARPi to recapitulate synthetic lethality in all tumors independently of their HR status. PMID:27559053

  12. Assessment of the frequency of regulatory T cells (CD4+CD25+CD127-) in children with hemophilia A: relation to factor VIII inhibitors and disease severity.

    Science.gov (United States)

    El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali

    2016-01-01

    A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

  13. [Relationship between factor VIII inhibitor development and polymorphisms of TNFα and CTLA-4 gene in Chinese Han patients with hemophilia A].

    Science.gov (United States)

    Zhang, Lu-lu; Yu, Zi-qiang; Zhang, Wei; Cao, Li-juan; Su, Jian; Bai, Xia; Ruan, Chang-geng

    2011-03-01

    To investigate the potential association between factor VIII inhibitor development and polymorphisms of tumor necrosis factor-α (TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A (HA). The single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FVIII concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism (RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously. In HA patients, G/G genotype, G/A genotype and A/A genotype were detected in 118 (84.3%), 18 (12.8%) and 4 cases (2.9%) respectively; C/C genotype, C/T genotype and T/T genotype were detected in 108 (77.2%), 30 (21.4%) and 2 cases (1.4%) respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant (P > 0.05). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 7.519, 95% CI = 3.168 - 17.844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 8.163, 95% CI = 2.521 - 26.434). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not (OR = 1.586, 95% CI = 0.729 - 3.450). TNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.

  14. Use of affinity-directed liquid chromatography-mass spectrometry to map the epitopes of a factor VIII inhibitor antibody fraction.

    Science.gov (United States)

    Griffiths, A E; Wang, W; Hagen, F K; Fay, P J

    2011-08-01

    Neutralizing factor (F) VIII antibodies develop in approximately 30% of individuals with hemophilia A and show specificity to multiple sites in the FVIII protein. Reactive epitopes to an immobilized IgG fraction prepared from a high-titer, FVIII inhibitor plasma were determined after immuno-precipitation (IP) of tryptic and chymotryptic peptides derived from digests of the A1 and A2 subunits of FVIIIa and FVIII light chain. Peptides were detected and identified using highly sensitive liquid chromatography-mass spectrometry (LC-MS). Coverage maps of the A1 subunit, A2 subunit and light chain represented 79%, 69% and 90%, respectively, of the protein sequences. Dot blots indicated that the inhibitor IgG reacted with epitopes contained within each subunit of FVIIIa. IP coupled with LC-MS identified 19 peptides representing epitopes from all FVIII A and C domains. The majority of peptides (10) were derived from the A2 domain. Three peptides mapped to the C2 domain, while two mapped to the A1 and A3 domains, and single peptides mapped to the a1 segment and C1 domain. Epitopes were typically defined by peptide sequences of < 12 residues. IP coupled with LC-MS identified extensive antibody reactivity at high resolution over the entire functional FVIII molecule and yielded sequence lengths of < 15 residues. A number of the peptides identified mapped to known sequences involved in functionally important protein-protein and protein-membrane interactions. © 2011 International Society on Thrombosis and Haemostasis.

  15. SUCCESSFUL LONG TERM ERADICATION OF FACTOR VIII INHIBITOR IN PATIENTS WITH ACQUIRED HAEMOPHILIA A IN SAUDI ARABIA

    Directory of Open Access Journals (Sweden)

    Galila F Zaher

    2012-01-01

    Full Text Available

    Acquired haemophilia A is a serious and potentially fatal bleeding disorder. Diagnosis is difficult and maybe delayed due to its rarity. The high mortality rate and the complex nature of treatment necessitate patient management at a haemophilia centre, where the required expertise and resources are available. Prompt diagnosis is crucial and early initiation of therapy could be life saving. Management includes initial control of bleeding followed by an approach to eradicate the coagulation factor inhibitor. In this paper we describe our local experience with acquired haemophilia A, which resulted in the successful control of major bleeding at presentation and eradication of inhibitors.

  16. SUCCESSFUL LONG TERM ERADICATION OF FACTOR VIII INHIBITOR IN PATIENTS WITH ACQUIRED HAEMOPHILIA A IN SAUDI ARABIA

    Directory of Open Access Journals (Sweden)

    Galila F Zaher

    2012-04-01

    Full Text Available Acquired haemophilia A is a serious and potentially fatal bleeding disorder. Diagnosis is difficult and maybe delayed due to its rarity. The high mortality rate and the complex nature of treatment necessitate patient management at a haemophilia centre, where the required expertise and resources are available. Prompt diagnosis is crucial and early initiation of therapy could be life saving. Management includes initial control of bleeding followed by an approach to eradicate the coagulation factor inhibitor. In this paper we describe our local experience with acquired haemophilia A, which resulted in the successful control of major bleeding at presentation and eradication of inhibitors.

  17. Effect of preoperative angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use on hemodynamic variables in pediatric patients undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Ajuba-Iwuji, Chinwe C; Puttreddy, Sahitya; Maxwell, Bryan G; Bembea, Melania; Vricella, Luca; Heitmiller, Eugenie

    2014-10-01

    Some have suggested that children undergoing cardiac surgery who receive angiotensin-converting enzyme (ACE) inhibitors experience a greater degree of hypotension after anesthesia induction and in the immediate postcardiopulmonary bypass period than children who did not receive these drugs. Therefore, we examined the effect of ACE inhibitor/angiotensin II receptor blocker (ARB) therapy on intraoperative hemodynamics and vasopressor use in pediatric patients undergoing cardiac surgery. In a retrospective cohort study of patients younger than 18 years who underwent cardiopulmonary bypass between March 1, 2010, and April 1, 2011, we compared intraoperative hemodynamics and vasopressor use between patients who received preoperative ACE inhibitor/ARB therapy and those who did not. The primary outcome was vasoactive infusion score after cardiopulmonary bypass. The occurrence of hypotension did not differ significantly between the ACE inhibitor/ARB group and the control group during induction of anesthesia or at any time point after cardiopulmonary bypass. At 0, 30, 60, and 90 minutes after cessation of cardiopulmonary bypass, patients on ACE inhibitor/ARB therapy tended to have a higher vasoactive infusion score (7.1, 7.6, 9.4, and 11.3) than patients in the control group (6.3, 6.1, 6.0, and 6.7). Although this difference became more pronounced over time, it did not reach statistical significance. The use of preoperative ACE inhibitors and ARBs in pediatric patients undergoing cardiac surgery did not significantly increase the incidence of hypotension after induction of anesthesia and did not increase significantly the vasoconstrictor requirements upon weaning from cardiopulmonary bypass; however, additional prospective studies are needed. © The Author(s) 2014.

  18. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A.

    Science.gov (United States)

    Gomperts, Edward

    2015-08-01

    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  19. Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A; Plosker, Greg L

    2007-01-01

    Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients

  20. Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

    LENUS (Irish Health Repository)

    Bacon, C L

    2011-05-01

    Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

  1. Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors.

    Science.gov (United States)

    Jdey, Wael; Thierry, Sylvain; Russo, Christophe; Devun, Flavien; Al Abo, Muthana; Noguiez-Hellin, Patricia; Sun, Jian-Sheng; Barillot, Emmanuel; Zinovyev, Andrei; Kuperstein, Inna; Pommier, Yves; Dutreix, Marie

    2017-02-15

    Purpose: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are PARP inhibitors (PARPi), which trigger synthetic lethality in tumors with homologous recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and nonhomologous end joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy.Experimental Design: We characterized the DNA repair inhibition activity of PARPi (olaparib) and AsiDNA by monitoring repair foci formation and DNA damage. We analyzed the cell survival to standalone and combined treatments of 21 tumor cells and three nontumor cells. In 12 breast cancer (BC) cell lines, correlation with sensitivity to each drug and transcriptome were statistically analyzed to identify resistance pathways.Results: Molecular analyses demonstrate that olaparib and AsiDNA respectively prevent recruitment of XRCC1 and RAD51/53BP1 repair enzymes to damage sites. Combination of both drugs increases the accumulation of unrepaired damage resulting in an increase of cell death in all tumor cells. In contrast, nontumor cells do not show an increase of DNA damage nor lethality. Analysis of multilevel omics data from BC cells highlighted different DNA repair and cell-cycle molecular profiles associated with resistance to AsiDNA or olaparib, rationalizing combined treatment. Treatment synergy was also confirmed with six other PARPi in development.Conclusions: Our results highlight the therapeutic interest of combining AsiDNA and PARPi to recapitulate synthetic lethality in all tumors independently of their HR status. Clin Cancer Res; 23(4); 1001-11. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. A randomized, double-blind, placebo-controlled trial of a COX-2 inhibitor (Rofecoxib) in patients undergoing coronary artery bypass surgery.

    Science.gov (United States)

    Wong, Poo-Sing; Asmat, Atasha; Chan, Yiong-Huak; Lee, Chuen-Neng

    2006-04-01

    The endothelium of patients with coronary artery disease shows increased expression of cyclooxygenase-2 (COX-2) during coronary artery bypass graft surgery (CABG) using cardiopulmonary bypass. This, together with serotonin, may lead to coronary microvessel spasm, which potentially, can contribute to myocardial ischemia and injury after surgery. We performed a randomized, double-blind, placebo-controlled trial in patients undergoing isolated CABG to determine whether short-term treatment with a selective COX-2 inhibitor, Rofecoxib (25 mg), given preoperatively and for 5 days after operation, can offer better myocardial protection in patients undergoing CABG by measuring serial cardiac troponin T (cTnT) levels. The study was powered to recruit 150 consecutive patients undergoing isolated CABG but the study was terminated prematurely by the worldwide withdrawal of rofecoxib. There were highly statistically significant (P<0.001) increases in cTnT in both groups at each time point (1, 6, 24 and 48 h after onset of cardiopulmonary bypass) compared to preoperative levels. cTnT levels were similar at all post-operative time points between the 2 groups. There is no evidence that short-term treatment with rofecoxib has a myocardial protective effect in patients undergoing CABG. There is also no evidence that its effect is deleterious to the myocardium in patients undergoing CABG.

  3. Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

    Science.gov (United States)

    Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori

    2017-08-31

    Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (Phemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

  4. Haemophilus influenzae biotype VIII.

    OpenAIRE

    Sottnek, F O; Albritton, W L

    1984-01-01

    Six Haemophilus influenzae strains could not be classified as biotypes I through VII. The strains were indole, urease, and ornithine decarboxylase negative. We propose that they be classified as biotype VIII, a previously unreported biotype.

  5. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  6. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

    Directory of Open Access Journals (Sweden)

    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  7. Influence of factor VIII level and its inhibitor titer on the therapeutic response to corticosteroids alone in the management of acquired hemophilia

    Science.gov (United States)

    Vautier, Mathieu; de Boysson, Hubert; Creveuil, Christian; Repesse, Yohan; Borel-Derlon, Annie; Troussard, Xavier; Damaj, Gandhi L.; Bienvenu, Boris; Gautier, Philippe; Aouba, Achille

    2016-01-01

    Abstract The treatment of acquired hemophilia (AH) involves discussing whether corticosteroids should be administered alone or combined with immunosuppressant drugs, which increase the risk of infection especially in elderly patients and/or those with autoimmunity or neoplastic diseases, who represent the target population of the disease. Prognostic factors highlighting adequate responses to corticosteroids alone must be identified for satisfactory clinical response and lower infectious risk. We aimed to evaluating the efficacy of corticosteroids alone in the management of AH depending on factor VIII (FVIII, ≥ or 20 Bethesda units per milliliter [BU/mL]) titer. We conducted a retrospective single-center study including 24 patients treated for AH with corticosteroids alone. Time to achieve partial remission (PR: absence of hemorrhage and FVIII levels >50 IU/dL) was significantly shorter in the FVIII ≥ 1 IU/dL group than in the FVIII  20 BU/mL group (15 [11–35] vs 41 [20–207] days, P = 0.003). In both subgroups, time to achieve complete remission (CR: negative INH and corticosteroids below 10 mg/d) was also significantly shorter than that observed in the opposite subgroups. INH titer, considered alone, did not affect the length of time to onset of PR or CR. CR and PR rates did not differ significantly depending on these variables. Our study suggests that in AH, patients with FVIII levels ≥1 IU/dL considered alone or combined with INH titer ≤20 BU/mL could be treated by corticosteroids alone, given that this subgroup of patients displayed faster therapeutic responses to this strategy. PMID:27902587

  8. Influence of factor VIII level and its inhibitor titer on the therapeutic response to corticosteroids alone in the management of acquired hemophilia: A retrospective single-center study.

    Science.gov (United States)

    Vautier, Mathieu; de Boysson, Hubert; Creveuil, Christian; Repesse, Yohan; Borel-Derlon, Annie; Troussard, Xavier; Damaj, Gandhi L; Bienvenu, Boris; Gautier, Philippe; Aouba, Achille

    2016-11-01

    The treatment of acquired hemophilia (AH) involves discussing whether corticosteroids should be administered alone or combined with immunosuppressant drugs, which increase the risk of infection especially in elderly patients and/or those with autoimmunity or neoplastic diseases, who represent the target population of the disease. Prognostic factors highlighting adequate responses to corticosteroids alone must be identified for satisfactory clinical response and lower infectious risk.We aimed to evaluating the efficacy of corticosteroids alone in the management of AH depending on factor VIII (FVIII, ≥ or 20 Bethesda units per milliliter [BU/mL]) titer.We conducted a retrospective single-center study including 24 patients treated for AH with corticosteroids alone.Time to achieve partial remission (PR: absence of hemorrhage and FVIII levels >50 IU/dL) was significantly shorter in the FVIII ≥ 1 IU/dL group than in the FVIII  20 BU/mL group (15 [11-35] vs 41 [20-207] days, P = 0.003). In both subgroups, time to achieve complete remission (CR: negative INH and corticosteroids below 10 mg/d) was also significantly shorter than that observed in the opposite subgroups. INH titer, considered alone, did not affect the length of time to onset of PR or CR. CR and PR rates did not differ significantly depending on these variables.Our study suggests that in AH, patients with FVIII levels ≥1 IU/dL considered alone or combined with INH titer ≤20 BU/mL could be treated by corticosteroids alone, given that this subgroup of patients displayed faster therapeutic responses to this strategy.

  9. Inhibitors

    Science.gov (United States)

    ... and exercise, immune tolerance therapy, and needs of older adults with hemophilia and an inhibitor. For more information, visit https://www.hemophilia.org/Events-Educational-Programs/Inhibitor-Education/Inhibitor-Education-Summits The NHF’s Inhibitor Education Summits ...

  10. Effect of urinary protease inhibitor (ulinastatin) on cardiopulmonary bypass: a meta-analysis for China and Japan.

    Science.gov (United States)

    Zhang, Yun; Zeng, Zhi; Cao, Yu; Du, Xiaodong; Wan, Zhi

    2014-01-01

    A meta-analysis was conducted to investigate the effects of ulinastatin treatment on adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Seven electronic databases were searched for reports of randomized, controlled trials conducted up to February 2014 in which patients undergoing cardiac surgery with CPB were administered ulinastatin in the perioperative period. Fifty-two studies with 2025 patients were retained for analysis. The results showed that the ulinastatin can attenuate the plasma levels of pro-inflammatory cytokines and enhance the anti-inflammatory cytokine levels in patients undergoing cardiac surgery with CPB. Meanwhile, the ulinastatin had a significant beneficial effect on myocardial injury. The mean differences (MD) and 95% confidence intervals (95% CI) of biochemical markers were -63.54 (-79.36, -47.72) for lactate dehydrogenase, -224.99 (-304.83, -145.14) for creatine kinase, -8.75 (-14.23, -3.28) for creatine kinase-MB, and -0.14 (-0.20, -0.09] for troponin I (all PChina and Japan undergoing cardiac surgery with CPB. Ulinastatin treatment may have protective effects on myocardial injury, and can increase the frequency of auto resuscitation, shorten the duration of intubation and mechanical ventilation.

  11. Effect of Urinary Protease Inhibitor (Ulinastatin) on Cardiopulmonary Bypass: A Meta-Analysis for China and Japan

    Science.gov (United States)

    Zhang, Yun; Zeng, Zhi; Cao, Yu; Du, Xiaodong; Wan, Zhi

    2014-01-01

    Objectives A meta-analysis was conducted to investigate the effects of ulinastatin treatment on adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Methods Seven electronic databases were searched for reports of randomized, controlled trials conducted up to February 2014 in which patients undergoing cardiac surgery with CPB were administered ulinastatin in the perioperative period. Results Fifty-two studies with 2025 patients were retained for analysis. The results showed that the ulinastatin can attenuate the plasma levels of pro-inflammatory cytokines and enhance the anti-inflammatory cytokine levels in patients undergoing cardiac surgery with CPB. Meanwhile, the ulinastatin had a significant beneficial effect on myocardial injury. The mean differences (MD) and 95% confidence intervals (95% CI) of biochemical markers were −63.54 (−79.36, −47.72) for lactate dehydrogenase, −224.99 (−304.83, −145.14) for creatine kinase, −8.75 (−14.23, −3.28) for creatine kinase-MB, and −0.14 (−0.20, −0.09] for troponin I (all P<0.01). However, neither hemodynamics nor cardiac function improved significantly, except that the MD and 95% CI of mean arterial pressure were 2.50 (0.19, 4.80) (P = 0.03). There were no statistically significant differences in the use of inotropes, postoperative bleeding, postoperative complications, the intensive care unit (ICU) stay, and the hospital stay; however, the frequency of auto resuscitation increased significantly (OR 1.98, 95%CI 1.19 to 3.30, P<0.01), the duration of intubation (MD −1.58, 95%CI −2.84 to −0.32, P<0.01) and the duration of mechanical ventilation (MD −3.29, 95%CI −4.41 to −2.17, P<0.01) shortened significantly in patients who were treated with ulinastatin. Conclusions Ulinastatin can reduce the plasma levels of pro-inflammatory cytokines and elevate anti-inflammatory cytokine in patients from China and Japan undergoing cardiac surgery with CPB. Ulinastatin

  12. Diagnosis of factor VIII deficiency.

    NARCIS (Netherlands)

    Verbruggen, B.; Meijer, P.; Novakova, I.; Heerde, W. Van

    2008-01-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show

  13. Heart bypass surgery

    Science.gov (United States)

    Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

  14. Gastric bypass surgery

    Science.gov (United States)

    ... Y gastric bypass; Gastric bypass - Roux-en-Y; Weight-loss surgery - gastric bypass; Obesity surgery - gastric bypass Patient Instructions Bathroom safety - adults Gastric bypass surgery - discharge Laparoscopic gastric banding - discharge ...

  15. Heart bypass surgery - discharge

    Science.gov (United States)

    Off-pump coronary artery bypass - discharge; OPCAB - discharge; Beating heart surgery - discharge; Bypass surgery - heart - discharge; CABG - discharge; Coronary artery bypass graft - discharge; Coronary artery ...

  16. Coronary Artery Bypass Grafting

    Science.gov (United States)

    ... Health Topics / Coronary Artery Bypass Grafting Coronary Artery Bypass Grafting What Is Coronary artery bypass grafting (CABG) ... multiple coronary arteries during one surgery. Coronary Artery Bypass Grafting Figure A shows the location of the ...

  17. Epitope mapping of inhibitory antibodies targeting the C2 domain of coagulation factor VIII by hydrogen-deuterium exchange mass spectrometry

    Science.gov (United States)

    Sevy, Alexander M.; Healey, John F.; Deng, Wei; Spiegel, P. Clint; Meeks, Shannon L.; Li, Renhao

    2014-01-01

    Summary Background The development of anti-factor VIII (fVIII) antibodies (inhibitors) is a significant complication in the management of patients with hemophilia A, leading to significant increases in morbidity and treatment cost. Using a panel of anti-fVIII monoclonal antibodies (MAbs) to different epitopes on fVIII, we recently have shown that epitope specificity, inhibitor kinetics, and time to maximum inhibition are more important than inhibitor titer in predicting response to fVIII and the combination of fVIII and recombinant factor VIIa. In particular, a subset of high-titer inhibitors responded to high dose fVIII, which would not be predicted based on their inhibitor titer alone. Thus the ability to quickly map the epitope spectrum of patient plasma using a clinically feasible assay may fundamentally change how clinicians approach the treatment of high-titer inhibitor patients. Objectives To map the epitopes of anti-fVIII MAbs, of which 3 are classical inhibitors and one non-classical, using hydrogen-deuterium exchange coupled with liquid chromatography-mass spectrometry (HDX-MS). Methods Binding epitopes of 4 MAbs targeting fVIII C2 domain were mapped using HDX-MS. Results The epitopes determined by HDX-MS are consistent with those obtained earlier through structural characterization and antibody competition assays. In addition classical and non-classical inhibitor epitopes could be distinguished using a limited subset of C2-derived peptic fragments. Conclusion Our results demonstrate the effectiveness and robustness of the HDX-MS method for epitope mapping and suggest a potential role of rapid mapping of fVIII inhibitor epitopes in facilitating individualized treatment of inhibitor patients. PMID:24152306

  18. Diagnosis of factor VIII deficiency.

    Science.gov (United States)

    Verbruggen, B; Meijer, P; Novákova, I; Van Heerde, W

    2008-07-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one-stage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

  19. War and peace: Factor VIII and the adaptive immune response.

    Science.gov (United States)

    Georgescu, Maria T; Lai, Jesse D; Hough, Christine; Lillicrap, David

    2016-03-01

    The development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitors) remains a major challenge for FVIII replacement therapy in hemophilia A patients. The adaptive immune response plays a crucial role in the development and maintenance of inhibitors. In this review, we focus on our current understanding of FVIII interactions with cells of the adaptive immune system and the phenotype of the resultant response. Additionally, we examine both current and novel FVIII tolerance induction methods that function at the level of the adaptive immune response. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit.

    Science.gov (United States)

    Gerstenberger, Brian S; Trzupek, John D; Tallant, Cynthia; Fedorov, Oleg; Filippakopoulos, Panagis; Brennan, Paul E; Fedele, Vita; Martin, Sarah; Picaud, Sarah; Rogers, Catherine; Parikh, Mihir; Taylor, Alexandria; Samas, Brian; O'Mahony, Alison; Berg, Ellen; Pallares, Gabriel; Torrey, Adam D; Treiber, Daniel K; Samardjiev, Ivan J; Nasipak, Brian T; Padilla-Benavides, Teresita; Wu, Qiong; Imbalzano, Anthony N; Nickerson, Jeffrey A; Bunnage, Mark E; Müller, Susanne; Knapp, Stefan; Owen, Dafydd R

    2016-05-26

    The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays.

  1. A bispecific antibody mimicking factor VIII in hemophilia A therapy.

    Science.gov (United States)

    Nogami, Keiji

    2016-06-01

    Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.

  2. Factor VIII therapy for hemophilia A: current and future issues.

    Science.gov (United States)

    Aledort, Louis; Ljung, Rolf; Mann, Kenneth; Pipe, Steven

    2014-06-01

    Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is managed with infusions of plasma-derived or recombinant factor (F) VIII. The primary considerations in FVIII replacement therapy today are the: 1) immunogenicity of FVIII concentrates, 2) role of longer-acting FVIII products, 3) prophylactic use of FVIII in children and adults with severe hemophilia A, and 4) affordability and availability of FVIII products. Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors, and expanding access to FVIII concentrates in developing countries are the major challenges confronting clinicians who care for patients with hemophilia A.

  3. Gene therapy for immune tolerance induction in hemophilia with inhibitors.

    Science.gov (United States)

    Arruda, V R; Samelson-Jones, B J

    2016-06-01

    The development of inhibitors, i.e. neutralizing alloantibodies against factor (F) VIII or FIX, is the most significant complication of protein replacement therapy for patients with hemophilia, and is associated with both increased mortality and substantial physical, psychosocial and financial morbidity. Current management, including bypassing agents to treat and prevent bleeding, and immune tolerance induction for inhibitor eradication, is suboptimal for many patients. Fortunately, there are several emerging gene therapy approaches aimed at addressing these unmet clinical needs of patients with hemophilia and inhibitors. Herein, we review the mounting evidence from preclinical hemophilia models that the continuous uninterrupted expression of FVIII or FIX delivered as gene therapy can bias the immune system towards tolerance induction, and even promote the eradication of pre-existing inhibitors. We also discuss several gene transfer approaches that directly target immune cells in order to promote immune tolerance. These preclinical findings also shed light on the immunologic mechanisms that underlie tolerance induction. © 2016 International Society on Thrombosis and Haemostasis.

  4. The impact of von Willebrand factor on factor VIII memory immune responses

    OpenAIRE

    Chen, Juan; Schroeder, Jocelyn A.; Luo, Xiaofeng; Shi, Qizhen

    2017-01-01

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis...

  5. Coronary Artery Bypass Surgery

    Science.gov (United States)

    ... don't help, you may need coronary artery bypass surgery. The surgery creates a new path for ... narrowed area or blockage. This allows blood to bypass (get around) the blockage. Sometimes people need more ...

  6. Heart bypass surgery - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100190.htm Heart bypass surgery - series—Normal anatomy To use the sharing ... Editorial team. Related MedlinePlus Health Topics Coronary Artery Bypass Surgery A.D.A.M., Inc. is accredited ...

  7. Coronary Artery Bypass

    Science.gov (United States)

    ... to 3 days in the Intensive Care Unit (ICU). Life After Bypass After bypass surgery, your doctor will recommend that you join a cardiac rehabilitation program. These programs help you make lifestyle changes ...

  8. Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A.

    Science.gov (United States)

    Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana; Healey, John F; Parker, Ernest T; Jacquemin, Marc; Krause, Manuela; Tiede, Andreas; Schwabe, Dirk; Lollar, Pete; Königs, Christoph

    2017-08-10

    Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. The analysis with HSA-fVIII domain proteins confirmed the results of the HSM approach but resulted in higher detection levels. The higher detection levels with HSA-fVIII domain proteins are a result of antibody cross-reactivity with human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-, and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63). Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed overlapping epitopes with murine C1-specific group A mAbs including 2A9. Mutational analyses identified distinct crucial binding residues for LE2E9 (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies was particularly observed in patients with AHA. Overall, our study demonstrates that the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral anti-fVIII immune response in acquired and congenital hemophilia inhibitor patients. © 2017 by The American Society of Hematology.

  9. Stark broadening parameter tables for Ar VIII

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1999-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 9 Ar VIII transitions as a function of temperature and perturber density.

  10. Stark broadening parameter tables for Kr VIII

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1999-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 6 Kr VIII multiplets as a function of temperature and perturber density.

  11. Recombinant porcine sequence factor VIII (rpFVIII) for acquired haemophilia A: practical clinical experience of its use in seven patients.

    Science.gov (United States)

    Tarantino, M D; Cuker, A; Hardesty, B; Roberts, J C; Sholzberg, M

    2017-01-01

    A recombinant porcine factor VIII B-domain-deleted product (rpFVIII; OBIZUR, Baxalta Incorporated, Deerfield, IL 60015, USA) was recently approved for treatment of bleeding episodes in adults with acquired haemophilia A (AHA) in the United States. To date, no clinical experience outside the registration study has been reported. To describe early clinical experience using rpFVIII for AHA. A retrospective chart review of seven patients with AHA treated with rpFVIII at four institutions from November 2014 to October 2015. The time to diagnosis of AHA ranged from 5 days to 6 weeks. Six major and one other bleed were treated with rpFVIII following unsatisfactory bypassing agent (BPA) therapy. Good haemostatic efficacy was seen in five of seven cases. rpFVIII loading doses of 100 (n = 6) or 200 U kg-1 (n = 1) increased FVIII activity from <1 to 9% at baseline to 109-650% within 0.25-7 h in six of seven cases. Subsequent median doses ranged from 30 to 100 U kg-1 for 3-26 days. No rpFVIII-related adverse events were reported. Three patients survived with inhibitor eradication, one with persistent inhibitor, two died with inhibitors present and one was discharged and later died from unrelated causes. rpFVIII showed good haemostatic efficacy with no recurrences in most cases, with consumption substantially less than in the registration study. Treatment decisions were based on FVIII activity levels and clinical assessment. The ability to titrate rpFVIII dose using FVIII activity was considered advantageous compared with BPA therapy. Notable delays in diagnosis were observed. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  12. Emerging Issues in Diagnosis, Biology, and Inhibitor Risk in Mild Hemophilia A.

    Science.gov (United States)

    Castaman, Giancarlo; Eckhardt, Corien; van Velzen, Alice; Linari, Silvia; Fijnvandraat, Karin

    2016-07-01

    Mild hemophilia A (MHA) is an X-linked bleeding disorder defined by factor VIII (FVIII) levels between 5 and 40 U/dL. Diagnosis occurs later in life compared with severe or moderate disease. Although bleeding episodes are especially posttraumatic, their unexpected occurrence may be potentially life threatening if diagnosis is missed or delayed. Desmopressin is the treatment of choice for MHA since it is cheap and safe, but a significant proportion of cases do not attain FVIII postinfusion greater than 50 U/dL, which is considered a safe level for major surgery. Thus, replacement therapy may be needed and is usually successful in MHA, but recent data indicate that this can be associated with the occurrence of inhibitors against FVIII, as for severe hemophilia A. However, in contrast to severe or moderate hemophilia A, patients with MHA have a lifelong risk of inhibitor formation. Inhibitors may change the clinical phenotype dramatically, as the inhibitor frequently cross-reacts with the patient's endogenous FVIII, reducing the endogenous FVIII plasma levels below 1 U/dL. Specific F8 missense mutations predispose to inhibitor development. Inhibitors are frequently provoked by intensive treatment with therapeutic FVIII concentrates (more than 5 consecutive exposure days). Bleeding in inhibitor patients may be treated with desmopressin, high doses of FVIII concentrate or FVIII bypassing agents. Many inhibitors disappear over time when no FVIII concentrate is administered. However, this does not imply that a patient is tolerant and an anamnestic reaction may occur when treatment with FVIII concentrate is again necessary. To eradicate, an inhibitor different strategies may be used: watchful waiting, immunosuppression, or immune tolerance induction regimen. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII.

    Science.gov (United States)

    Hu, Chuhong; Cela, Racel G; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S

    2011-02-01

    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.

  14. Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII.

    Science.gov (United States)

    Schmidbauer, Stefan; Witzel, Reinhild; Robbel, Lars; Sebastian, Petra; Grammel, Nicolas; Metzner, Hubert J; Schulte, Stefan

    2015-08-01

    rVIII-SingleChain is a novel recombinant single-chain factor VIII (FVIII) construct, comprising covalently bonded heavy and light chains. Post-translational modifications of FVIII affect physicochemical parameters, including hydrophobicity and charge. The most relevant post-translational modifications of FVIII products are N-glycosylation of asparagine residues and tyrosine sulphations. Here, the physicochemical properties, thrombin cleavage products and post-translational modifications of rVIII-SingleChain were investigated and compared against commercially available recombinant FVIII (rFVIII) products with a predominant two-chain structure (B-domain deleted rFVIII and full-length rFVIII). rVIII-SingleChain was expressed in Chinese hamster ovary (CHO) cells and purified by chromatographic methods. Physicochemical properties of rVIII-SingleChain or thrombin-derived cleavage products were assessed using size-exclusion chromatography, reversed-phase chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis. Analysis of the respective carbohydrate structures was performed after release of N-glycans by PNGase F followed by fluorescence labelling and high-performance liquid chromatography. Proteolysis by trypsin generated the corresponding peptides, which were analysed for sulphated tyrosines by liquid chromatography-electrospray ionisation time of flight-mass spectrometry. rVIII-SingleChain was shown to be of high purity and homogeneity, and presented a well-defined single-chain molecule with predominant β-sheet conformation. The coagulation-relevant thrombin-activation products of rVIII-SingleChain were comparable with those obtained by activation of commercially available rFVIII products. rVIII-SingleChain post-translational modifications were similar to other CHO cell-derived rFVIII products for N-glycopattern and tyrosine sulphation. In conclusion, rVIII-SingleChain is of high homogeneity and purity, and provides an expected cleavage pattern on

  15. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  16. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  17. Arterial bypass leg - slideshow

    Science.gov (United States)

    ... presentations/100155.htm Arterial bypass leg - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  18. Thrombin During Cardiopulmonary Bypass

    National Research Council Canada - National Science Library

    Edmunds, L. Henry; Colman, Robert W

    2006-01-01

    Cardiopulmonary bypass (CPB) ignites a massive defense reaction that stimulates all blood cells and five plasma protein systems to produce a myriad of vasoactive and cytotoxic substances, cell-signaling molecules...

  19. Cardiopulmonary bypass in pregnancy

    National Research Council Canada - National Science Library

    Kapoor, MukulChandra

    2014-01-01

      Cardiac surgery carried out on cardiopulmonary bypass (CPB) in a pregnant woman is associated with poor neonatal outcomes although maternal outcomes are similar to cardiac surgery in non-pregnant women...

  20. Cardiopulmonary bypass and hemostasis

    NARCIS (Netherlands)

    Eijsman, Leon

    1992-01-01

    In chapter 1, we recalled that intracardiac defects can only be corrected when cardiopulmonary circulation is maintained by extracorporeal criculation and ventilation. To prevent clot formation in this artificial circuit, the socalled cardiopulmonary bypass (CPB), we completely depend on the

  1. Gastric bypass surgery - discharge

    Science.gov (United States)

    ... heart disease Gastric bypass surgery Laparoscopic gastric banding Obesity Obstructive sleep apnea - adults Type 2 diabetes Patient Instructions Getting out of bed after surgery Weight-loss surgery - after - what to ask your doctor Weight- ...

  2. Bypassing damaged nervous tissue

    CERN Document Server

    Shneider, M N

    2016-01-01

    We show the principal ability of bypassing damaged demyelinated portions of nervous tissue, thereby restoring its normal function for the passage of action potentials. We carry out a theoretical analysis on the basis of the synchronization mechanism of action potential propagation along a bundle of neurons, proposed recently in [1]. And we discuss the feasibility of implement a bypass to restore damaged nervous tissue and creating an artificial neuron network.

  3. Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

    Science.gov (United States)

    Valentino, L A; Holme, P A

    2015-11-01

    Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings. © 2015 John Wiley & Sons Ltd.

  4. [Acquired coagulant factor inhibitors].

    Science.gov (United States)

    Nogami, Keiji

    2015-02-01

    Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding symptoms due to decreases in the corresponding factor (s) which result from the appearance of autoantibodies against coagulation factors (inhibitor). This disease is quite different from congenital coagulation factor deficiencies based on genetic abnormalities. In recent years, cases with this disease have been increasing, and most have anti-factor VIII autoantibodies. The breakdown of the immune control mechanism is speculated to cause this disease since it is common in the elderly, but the pathology and pathogenesis are presently unclear. We herein describe the pathology and pathogenesis of factor VIII and factor V inhibitors. Characterization of these inhibitors leads to further analysis of the coagulation process and the activation mechanisms of clotting factors. In the future, with the development of new clotting examination method (s), we anticipate that further novel findings will be obtained in this field through inhibitor analysis. In addition, detailed elucidation of the coagulation inhibitory mechanism possibly leading to hemostatic treatment strategies for acquired coagulation factor disorders will be developed.

  5. High-affinity, noninhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors.

    Science.gov (United States)

    Batsuli, Glaivy; Deng, Wei; Healey, John F; Parker, Ernest T; Baldwin, W Hunter; Cox, Courtney; Nguyen, Brenda; Kahle, Joerg; Königs, Christoph; Li, Renhao; Lollar, Pete; Meeks, Shannon L

    2016-10-20

    Inhibitor formation in hemophilia A is the most feared treatment-related complication of factor VIII (fVIII) therapy. Most inhibitor patients with hemophilia A develop antibodies against the fVIII A2 and C2 domains. Recent evidence demonstrates that the C1 domain contributes to the inhibitor response. Inhibitory anti-C1 monoclonal antibodies (mAbs) have been identified that bind to putative phospholipid and von Willebrand factor (VWF) binding epitopes and block endocytosis of fVIII by antigen presenting cells. We now demonstrate by competitive enzyme-linked immunosorbent assay and hydrogen-deuterium exchange mass spectrometry that 7 of 9 anti-human C1 mAbs tested recognize an epitope distinct from the C1 phospholipid binding site. These mAbs, designated group A, display high binding affinities for fVIII, weakly inhibit fVIII procoagulant activity, poorly inhibit fVIII binding to phospholipid, and exhibit heterogeneity with respect to blocking fVIII binding to VWF. Another mAb, designated group B, inhibits fVIII procoagulant activity, fVIII binding to VWF and phospholipid, fVIIIa incorporation into the intrinsic Xase complex, thrombin generation in plasma, and fVIII uptake by dendritic cells. Group A and B epitopes are distinct from the epitope recognized by the canonical, human-derived inhibitory anti-C1 mAb, KM33, whose epitope overlaps both groups A and B. Antibodies recognizing group A and B epitopes are present in inhibitor plasmas from patients with hemophilia A. Additionally, group A and B mAbs increase fVIII clearance and are pathogenic in a hemophilia A mouse tail snip bleeding model. Group A anti-C1 mAbs represent the first identification of pathogenic, weakly inhibitory antibodies that increase fVIII clearance. © 2016 by The American Society of Hematology.

  6. Heat transfer burnout of Mark VIII fuel

    Energy Technology Data Exchange (ETDEWEB)

    Bernath, L.

    1956-08-01

    The operating conditions to which the special Mark VIII quatrefoils will be exposed during the proposed piloting program have been compared with the conditions required to cause burnout, using an established method of calculating these conditions. The results of this comparison permit the following conclusions to be drawn: (1) With normal flow of coolant through the special elements the heat flux to be encountered in the R-8 cycle (1400 MW) will be 70% or that required to cause burnout (30% margin from burnout). (2) With a reduction of coolant flow to 82% of normal through one tube of a special element, burnout of that fuel column is possible in the R-8 cycle. (3) In the R-6 cycle (1280 MW), the margin from burnout in the special Mark VIII quatrefoils is 42% with full flow and 20% with the above reduced coolant flow. A similar comparison of operating conditions predicted for the L-3 cycle (full Mark VIII charge) shows that, even at the highest power level (1250 MW), the margin from burnout is greater than 55% with normal flow and 40% with reduced flow.

  7. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

    Directory of Open Access Journals (Sweden)

    Alexandra Sherman

    2017-11-01

    Full Text Available Hemophilia A (coagulation factor VIII deficiency is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors” remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg, in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A.

  8. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

    Science.gov (United States)

    Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

    2017-01-01

    Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

  9. Rural Bypass for Elective Surgeries.

    Science.gov (United States)

    Weigel, Paula A M; Ullrich, Fred; Finegan, Chance N; Ward, Marcia M

    2017-04-01

    Rural bypass of Critical Access Hospitals (CAHs) for elective inpatient and outpatient surgical procedures has not been studied. Residents choosing to have their elective surgeries elsewhere, when the local CAH provides those surgical services, erode their rural hospital's financial base. The purpose of this research is to describe the elective surgical bypass rate, the procedures most commonly bypassed by rural residents, the distribution of volume among CAHs that offer elective surgical services, and factors predictive of bypass. A sample of elective surgery discharges was created from the 2011 Healthcare Cost and Utilization Project State Inpatient Databases and State Ambulatory Surgery Databases for Colorado, North Carolina, Vermont, and Wisconsin. Frequencies of procedures bypassed and CAH volume distribution were performed. Logistic regression was used to model factors associated with rural bypass for elective surgical care. The rural bypass rate for elective surgical procedures is 48.4%. Procedures bypassed most are operations on the musculoskeletal system, eye, and digestive system. Annual volume distribution for elective surgical procedures among CAHs varied widely. Patients who are younger, medically complex, at higher surgical risk, and have private insurance are at higher odds of bypass. Patients are also more likely to bypass low-volume hospitals. Rural hospitals should consider developing surgical services that are performed electively and on an outpatient basis that are attractive to a broader rural population. CAHs that already offer elective surgical procedures and yet who are still bypassed must examine the mutable factors that drive bypass behavior. © 2015 National Rural Health Association.

  10. The Best Bypass Surgery Trial

    DEFF Research Database (Denmark)

    Møller, Christian H; Jensen, Birte Østergaard; Gluud, Christian

    2007-01-01

    Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have...

  11. Aortic valve bypass

    DEFF Research Database (Denmark)

    Lund, Jens T; Jensen, Maiken Brit; Arendrup, Henrik

    2013-01-01

    In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI...

  12. Artery Bypass Grafting

    African Journals Online (AJOL)

    Unknown

    nary artery disease (CAD) was coronary artery bypass graft (CAB G) using a segment of saphenous vein interposed between the ascend- ing aorta and the coronary artery distal to the obstructing lesion. This was performed by David Sabiston of Duke University in 1962. With the use of the recently developed technique of ...

  13. Preparing for ENDF/B-VIII

    Science.gov (United States)

    Brown, David

    2017-09-01

    Although the next major release of the ENDF/B library is not due until the 2017-2018 time frame, ENDF/B-VIII is already positioned to become the most important release of the library in some time. ENDF/B-VIII will be built around the Neutron Reaction Standards as well as the 1H, 16O, 56Fe, 235U, 238U and 239Pu evaluations developed as part of the Coordinated International Evaluation Library Organization (CIELO) pilot project. In this contribution, we summarize these improvements as well as the many other improvements to ENDF that have already been made or are scheduled to be made in the next year. Improvements already included in the ENDF/B-VIII beta releases: • Aggressive use of the flexible and physically correct LRF=7 resolved resonance format in 12 updated evaluations (35,37Cl, 40Ca, 54,56,57Fe, 63,65Cu and 182,183,184,186W) • Thermal capture gammas from the EGAF project (6,7Li, 11B, 19F, 23Na, 27Al, 28Si, 35,37Cl) • Thermal Scattering Law evaluations from NCSU (α and β phase SiO2, SiC, lucite, BeO, and polyethylene) and from the CAB-CNL collaboration (heavy and light water) • Many new evaluations in the neutron sublibrary (n, 12,13C, 40Ar, 54,57,58Fe, 58,59,60,61,62,64Ni, 63,65Cu, 73As, 120Sn, 236m1Np) Inclusion of Red Cullen's EPICS2014 library, updating the photo-atomic, electron and atomic-relaxation sublibraries. Many improvements are planned in the next year including new evaluations such as charged particle evaluations translated from LLNL's ECPL. In addition to these major changes, ENDF/B-VIII will be the first official library released simultaneously in the legacy ENDF-6 and the newly developed Generalized Nuclear Data (GND) formats.

  14. piggyBac-mediated phenotypic correction of factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    Janice M Staber

    2014-01-01

    Full Text Available Hemophilia A, caused by a deficiency in factor VIII (FVIII, is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integrated transgene offers the possibility of long term expression. We engineered the DNA transposon-based vector, piggyBac (PB, to carry a codon-optimized B-domain deleted human FVIII cDNA. Evaluation of gene transfer efficiency in FVIII null mice demonstrated that PB containing the FVIII cDNA, delivered via hydrodynamic injection to immunocompetent hemophilia mice, conferred persistent gene expression, attaining mean FVIII activity of approximately 60% with 3/19 developing inhibitors. In addition to efficacious expression, a goal of gene transfer-based therapies is to develop vectors with low toxicity. To assess endoplasmic reticulum stress in hepatocytes stably expressing the transgene, we evaluated levels of ER stress markers via qPCR and found no evidence of cell stress. To evaluate phenotypic correction, a tail clip assay performed at the end of the study revealed reduced blood loss. These data demonstrate that PB can be used to achieve sustained FVIII expression and long-term therapeutic benefit in a mouse model.

  15. 12 CFR 611.1137 - Title VIII service corporations.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Title VIII service corporations. 611.1137 Section 611.1137 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ORGANIZATION Service... authorities granted under title VIII of the Act to act as an agricultural mortgage marketing facility. (b) How...

  16. The influence of prophylactic factor VIII in severe hemophilia A

    Science.gov (United States)

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

    2013-01-01

    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  17. Bypass: A Memoir

    OpenAIRE

    Amato, Joseph A.

    2000-01-01

    This inquiry into matters of heart, conducted under the shadows of pending surgery, awakens themes of boyhood, education, and marriage and prompt questions about loyalty to a deceased father, connections with immigrant grandparents, loss and rediscovery of faith, and solitude versus community. A medical narrative, the book also chronicles a span of contemporary American life. Throughout Amato's account, the consistent reminder of his upcoming bypass invites readers to reflect on their own liv...

  18. Relationship of femorodistal bypass patency to clinical outcome. Iloprost Bypass International Study Group

    DEFF Research Database (Denmark)

    Watson, H R; Schroeder, T V; Simms, M H

    1999-01-01

    To investigate the relationship between bypass patency, limb survival and clinical symptoms after femorodistal bypass procedures.......To investigate the relationship between bypass patency, limb survival and clinical symptoms after femorodistal bypass procedures....

  19. Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy.

    Science.gov (United States)

    Finn, Jonathan D; Ozelo, Margareth C; Sabatino, Denise E; Franck, Helen W G; Merricks, Elizabeth P; Crudele, Julie M; Zhou, Shangzhen; Kazazian, Haig H; Lillicrap, David; Nichols, Timothy C; Arruda, Valder R

    2010-12-23

    Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-existing inhibitors. To determine whether sustained endogenous expression of FVIII could eradicate inhibitors, we injected adeno-associated viral vectors encoding canine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs. In 3 dogs, a transient increase in inhibitor titers (up to 7 Bethesda Units [BU]) at 2 weeks was followed by continuous decline to complete disappearance within 4-5 weeks. Subsequently, an increase in cFVIII levels (1.5%-8%), a shortening of clotting times, and a reduction (> 90%) of bleeding episodes were observed. Immune tolerance was confirmed by lack of antibody formation after repeated challenges with cFVIII protein and normal protein half-life. A fourth dog exhibited a strong early anamnestic response (216 BU), with slow decline to 0.8 BU and cFVIII antigen detection by 18 months after vector delivery. These data suggest that liver gene therapy has the potential to eradicate inhibitors and could improve the outcomes of hemophilia A patients.

  20. A new recombinant factor VIII: from genetics to clinical use

    Directory of Open Access Journals (Sweden)

    Santagostino E

    2014-12-01

    Full Text Available Elena Santagostino Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy Abstract: Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A. Keywords: hemophilia A, recombinant factor VIII, turoctocog alfa, purification, inhibitor, safety

  1. Bilateral Renal Vein Thrombosis due to Elevated Factor VIII Levels.

    Science.gov (United States)

    Patole, Shalom; Ramya, I

    2015-08-01

    Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use. © Journal of the Association of Physicians of India 2011.

  2. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  3. Your diet after gastric bypass surgery

    Science.gov (United States)

    Gastric bypass surgery - your diet; Obesity - diet after bypass; Weight loss - diet after bypass ... completely. Some of these are pasta, rice, bread, raw vegetables, and meats. Adding a low-fat sauce, ...

  4. Coronary Artery Bypass

    Directory of Open Access Journals (Sweden)

    Kadri Ceberut

    2011-01-01

    Full Text Available Ancient schwannoma is a rare variant of neural tumors though rarely seen in the thorax. The combination with coronary artery diseases is also rare. Here we describe a 66 year-old male who had undergone one-stage combined surgery for thoracic ancient schwannomas removal and coronary artery disease. The masses were, respectively, 13 cm in the middle mediastinum and 5 cm in diameter originating from the intercostal nerve. The tumors were successfully removed using sternotomy, and then a coronary artery bypass grafting was performed. Here we discuss this rare tumor in relation to the relevant literature.

  5. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII

    Science.gov (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C

    2016-01-01

    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  6. Stark broadening parameter tables for K VIII and K IX

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1998-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 4 K VIII and 30 K IX multiplets as a function of temperature and perturber density.

  7. Heart bypass surgery - minimally invasive - discharge

    Science.gov (United States)

    Minimally invasive direct coronary artery bypass - discharge; MIDCAB - discharge; Robot assisted coronary artery bypass - discharge; RACAB - discharge; Keyhole heart surgery - discharge; Coronary artery disease - MIDCAB discharge; CAD - ...

  8. Spiritual Bypass: A Preliminary Investigation

    Science.gov (United States)

    Cashwell, Craig S.; Glosoff, Harriet L.; Hammond, Cheree

    2010-01-01

    The phenomenon of spiritual bypass has received limited attention in the transpersonal psychology and counseling literature and has not been subjected to empirical inquiry. This study examines the phenomenon of spiritual bypass by considering how spirituality, mindfulness, alexithymia (emotional restrictiveness), and narcissism work together to…

  9. Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.

    Science.gov (United States)

    Aspatwar, Ashok; Tolvanen, Martti E E; Jokitalo, Eija; Parikka, Mataleena; Ortutay, Csaba; Harjula, Sanna-Kaisa E; Rämet, Mika; Vihinen, Mauno; Parkkila, Seppo

    2013-02-01

    Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans.

  10. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking

    OpenAIRE

    Ebberink, Eduard H T M; Bouwens, Eveline A. M.; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Alexander B. Meijer; Mertens, Koen

    2017-01-01

    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intrace...

  11. Thrombin inhibitors from different animals.

    Science.gov (United States)

    Tanaka-Azevedo, A M; Morais-Zani, K; Torquato, R J S; Tanaka, A S

    2010-01-01

    Venous and arterial thromboembolic diseases are still the most frequent causes of death and disability in high-income countries. Clinical anticoagulants are inhibitors of enzymes involved in the coagulation pathway, such as thrombin and factor X(a). Thrombin is a key enzyme of blood coagulation system, activating the platelets, converting the fibrinogen to the fibrin net, and amplifying its self-generation by the activation of factors V, VIII, and XI. Thrombin has long been a target for the development of oral anticoagulants. Furthermore, selective inhibitors of thrombin represent a new class of antithrombotic agents. For these reasons, a number of specific thrombin inhibitors are under evaluation for possible use as antithrombotic drugs. This paper summarizes old and new interests of specific thrombin inhibitors described in different animals.

  12. Thrombin Inhibitors from Different Animals

    Directory of Open Access Journals (Sweden)

    A. M. Tanaka-Azevedo

    2010-01-01

    Full Text Available Venous and arterial thromboembolic diseases are still the most frequent causes of death and disability in high-income countries. Clinical anticoagulants are inhibitors of enzymes involved in the coagulation pathway, such as thrombin and factor Xa. Thrombin is a key enzyme of blood coagulation system, activating the platelets, converting the fibrinogen to the fibrin net, and amplifying its self-generation by the activation of factors V, VIII, and XI. Thrombin has long been a target for the development of oral anticoagulants. Furthermore, selective inhibitors of thrombin represent a new class of antithrombotic agents. For these reasons, a number of specific thrombin inhibitors are under evaluation for possible use as antithrombotic drugs. This paper summarizes old and new interests of specific thrombin inhibitors described in different animals.

  13. Challenges and successes in the treatment of hemophilia: the story of a patient with severe hemophilia A and high-titer inhibitors

    Directory of Open Access Journals (Sweden)

    Saba HI

    2012-05-01

    Full Text Available Hussain I Saba, Duc Quang Tran, JrDepartment of Medicine, University of South Florida Medical Center, Tampa, FL, USAAbstract: In the past, patients with severe hemophilia have suffered a substantially reduced quality of life with frequent bleeding episodes, disabling arthropathy, and shorter life expectancy. In addition, methods of treatment and management have been costly and time-consuming, and have placed a considerable burden on patients' physical and psychological well-being. With the advent of the on-demand therapy and prophylactic treatment paradigm, patients have been able to receive care with less interruption of daily activities. Treatments may be more challenging for hemophiliacs with inhibitors to replacement factor; however, recent advances in the use of bypassing agents and immune tolerance therapy have enabled them to aggressively manage their disease while maintaining their independence. This review focuses on the challenges of treating such a severe hemophiliac through examination of the lifetime experience of a young adult male with a severe form of congenital hemophilia A. At this stage of his life, the patient has minimal disabilities and is inhibitor-free through optimal care and strong family support. His aspiration to pursue a productive life has led him to a career in medicine. After receiving his medical degree, he pursued a specialty in the treatment of hemophilia. By assisting other hemophilia patients, he exemplifies both the rewards of persevering through episodes of bleeding and other complications and the fact that disabilities can be minimized when managed meticulously and in a timely fashion to enable a productive and dignified life.Keywords: hemophilia, quality of life, factor VIII inhibitors, hemophilia treatment center, early treatment, bypassing agent

  14. Analysis of inversions in the factor VIII gene in Spanish hemophilia A patients and families

    Energy Technology Data Exchange (ETDEWEB)

    Domenech, M.; Tizzano, E.; Baiget, M. [Hospital de Sant Pau, Barcelona (Spain); Altisent, C. [Hospital Vall d`Hebron, Barcelona (Spain)

    1994-09-01

    Intron 22 is the largest intron of the factor VIII gene and contains a CpG island from which two additional transcripts originate. One of these transcripts corresponds to the F8A gene which have telomeric extragenic copies in the X chromosome. An inversion involving homologous recombination between the intragenic and the distal or proximal copies of the F8A gene has been recently described as a common cause of severe hemophilia A (HA). We analyzed intron 22 rearrangements in 195 HA patients (123 familial and 72 sporadic cases). According to factor VIII levels, our sample was classified as severe in 114 cases, moderate in 29 cases and mild in 52 cases. An intron 22 (F8A) probe was hybridized to Southern blots of BcII digested DNA obtained from peripheral blood. A clear pattern of altered bands identifies distal or proximal inversions. We detected an abnormal pattern identifying an inversion in 49 (25%) of the analyzed cases. 43% of severe HA patients (49 cases) showed an inversion. As expected, no inversion was found in the moderate and mild group of patients. We found a high proportion (78%) of the distal rearrangement. From 49 identified inversions, 33 were found in familial cases (27%), while the remaining 15 were detected in sporadic patients (22%) in support that this mutational event occurs with a similar frequency in familial or sporadic cases. In addition, we detected a significant tendency of distal inversion to occur more frequently in familial cases than in sporadic cases. Inhibitor development to factor VIII was documented in approximately 1/3 of the patients with inversion. The identification of such a frequent molecular event in severe hemophilia A patients has been applied in our families to carrier and prenatal diagnosis, to determine the origin of the mutation in the sporadic cases and to detect the presence of germinal mosaicism.

  15. Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Schulze, Costas J; Castro, Michele M; Kandasamy, Arulmozhi D; Cena, Jonathan; Bryden, Courtney; Wang, Shoa H; Koshal, Arvind; Tsuyuki, Ross T; Finegan, Barry A; Schulz, Richard

    2013-11-01

    Matrix metalloproteinase-2 proteolyzes intracellular proteins in the heart and induces acute myocardial contractile dysfunction in ischemia-reperfusion injury. Doxycycline, a matrix metalloproteinase inhibitor, prevented matrix metalloproteinase-2-induced troponin I cleavage in rat hearts and improved contractile function following ischemia-reperfusion. In patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass, increased atrial matrix metalloproteinase-2 activity was inversely correlated with cardiac mechanical function at 3 hours reperfusion. We performed a study in patients with coronary artery disease undergoing primary elective coronary artery bypass graft surgery with cardiopulmonary bypass to determine whether doxycycline reduces cardiac mechanical dysfunction, matrix metalloproteinase activity, and troponin I degradation after reperfusion. Randomized, double-blinded, placebo-controlled study. University of Alberta Hospital. Forty-two patients with coronary artery disease undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Patients were randomized to receive either oral administration of 20 mg of doxycycline or matching placebo pill twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days. Left ventricular stroke work index was examined prior to cardiopulmonary bypass and at 24 hours reperfusion. Right atrial biopsies were collected before cardiopulmonary bypass and 10 minutes after aortic cross-clamp release to determine matrix metalloproteinase-2 activity and troponin I level. Blood was collected to determine matrix metalloproteinase activity and interleukin-6, C-reactive protein, and troponin I levels. Cardiac 72-kDa matrix metalloproteinase-2 activity was lower upon reperfusion in biopsies from the doxycycline group (p = 0.01), and the increase of matrix metalloproteinase-2 activity in the placebo group due to reperfusion did not appear in the

  16. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

    Science.gov (United States)

    Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

    2017-12-28

    Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with

  17. Reconnaissance Report Yolo Bypass, California

    National Research Council Canada - National Science Library

    1992-01-01

    The purpose of this study was to investigate flooding and related water resources problems associated with the Yolo Bypass and determine the Federal interest in proceeding into feasibility phase studies...

  18. Heart bypass surgery - minimally invasive

    Science.gov (United States)

    ... and lifestyle Cholesterol - drug treatment Controlling your high blood pressure Dietary fats explained Fast food tips Heart attack - discharge Heart attack - what to ask your doctor Heart bypass surgery - minimally invasive - discharge Heart disease - risk factors Heart pacemaker - discharge ...

  19. The economics of inpatient on-demand treatment for haemophilia with high-responding inhibitors: a US retrospective data analysis.

    Science.gov (United States)

    Pokras, S M; Petrilla, A A; Weatherall, J; Lee, W C

    2012-03-01

    Inpatient costs comprise >50% of annual healthcare costs for haemophilia patients with inhibitors but no reports exist on inpatient resource use and costs at a US national level. To quantify inpatient resource use and costs for on-demand treatment of bleeds of US haemophilia patients with inhibitors and compare costs and treatment duration between Factor VIII bypassing agents (BAs). Stays with haemophilia A from 2003-2008 were identified from inpatient billing records. Presence of inhibitors was inferred through use of BA; recombinant activated Factor VII and plasma-derived activated prothrombin complex concentrate. Duration and number of infusions of BA, length of stay, use of opioid-containing analgesics and costs were assessed and compared. Among 1322 stays mean BA treatment duration was 4.6 days with 4.9 infusions, 6.1 nights spent in hospital, and 58% administered opioid-containing analgesics. In unadjusted analyses there were significant differences in the above mentioned outcomes by BA use, reflecting underlying differences between the two patient populations. Average inpatient costs were $82,911. In adjusted analyses, African-American race, greater disease severity, hospital region outside the southern US and older age (cost model only) were significant predictors of longer BA treatment duration and higher costs. The economic burden of inpatient on-demand treatment of haemophilia with inhibitors is substantial and is associated with lengthy stays, high costs and inadequate pain relief. Availability of more effective BAs could reduce the need for re-treatment, reducing treatment costs and other medical costs, while improving health related quality of life. © 2011 Blackwell Publishing Ltd.

  20. Uso de corticóide como inibidor da resposta inflamatória sistêmica induzida pela circulação extracorpórea Corticoid as an inhibitor of systemic inflammatory response, induced by cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Luiz Antonio BRASIL

    1999-07-01

    diferença estatisticamente significativa entre os dois grupos. CONCLUSÕES: A metilprednisolona inibiu significantemente a liberação de citocinas pró-inflamatórias principalmente o TNFa. Os efeitos sistêmicos adversos decorrentes da reação inflamatória pós-CEC foram atenuados com o uso do corticóide.Cardiopulmonary bypass (CPB induces the development of a systemic inflammatory response syndrome, with the release of cytokines that are responsible for many clinical manifestations. PURPOSE: The purpose of the study was to observe the release of the cytokines - tumor necrosis factor alpha (TNFa and Interleukine-6 (IL-6, and to verify the clinical alterations produced in patients undergoing myocardial revascularization with CPB, with or without corticoids. MATERIAL AND METHODS: Thirty patients were studied - 15 used corticoid (methylprednisolone, 30 mg/kg -Group I and 15 did not (Group II. Serial blood samples were collected and the TNFa and IL-6 release were analyzed, as well as the leukocyte count, erythrocyte sedimentation rate and glycemia. The blood pressure, cardiac rate, temperature, postoperative bleeding, orotracheal tubing time and inotropic drug requirement were also compared. Statistical significance was assumed when p £ 0.05. RESULTS: In Group I TNFa was not detected and IL-6 was detected in 13 patients, with levels ranging from 8.6 to 101.8 pg/ml. In Group II TNFa was detected in 13 patients, with levels between 5.4 and 231.0 pg/ml. The IL-6 in this group was detected in 15 patients, with higher levels than those in Group I, varying between 5.5 and 2569.0 pg/ml. The Group I patients had higher medium blood pressure (7.9 ± 0.5 vs 7.3 ± 0.4 mmHg and lower inotropic drug requirement (5 vs 11. They evolved with less tachycardia (105.6 ± 5.9 vs 109.3 ± 7.2 bpm, lower temperature (36.5 ± 0.2 vs 37.3 ± 0.2°C, lower postoperative bleeding, (576.6 ± 119.5 vs 810.0 ± 176.2 ml, shorter orotracheal tubing time (11.0 ± 2.0 vs 14.6 ± 2.9 hs and lower

  1. Analysis of factor VIII gene inversions in 164 unrelated hemophilia A families

    Energy Technology Data Exchange (ETDEWEB)

    Vnencak-Jones, L.; Phillips, J.A. III; Janco, R.L. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

    1994-09-01

    Hemophilia A is an X-linked recessive disease with variable phenotype and both heterogeneous and wide spread mutations in the factor VIII (F8) gene. As a result, diagnostic carrier or prenatal testing often relies upon laborious DNA linkage analysis. Recently, inversion mutations resulting from an intrachromosomal recombination between DNA sequences in one of two A genes {approximately}500 kb upstream from the F8 gene and a homologous A gene in intron 22 of the F8 gene were identified and found in 45% of severe hemophiliacs. We have analyzed banked DNA collected since 1986 from affected males or obligate carrier females representing 164 unrelated hemophilia A families. The disease was sporadic in 37%, familial in 54% and in 10% of families incomplete information was given. A unique deletion was identified in 1/164, a normal pattern was observed in 110/164 (67%), and 53/164 (32%) families had inversion mutations with 43/53 (81%) involving the distal A gene (R3 pattern) and 10/53 (19%) involving the proximal A gene (R2 pattern). While 19% of all rearrangements were R2, in 35 families with severe disease (< 1% VIII:C activity) all 16 rearrangements seen were R3. In 18 families with the R3 pattern and known activities, 16 (89%) had levels < 1%, with the remaining 2 families having {le} 2.4% activity. Further, 18 referrals specifically noted the production of inhibitors and 8/18 (45%) had the R3 pattern. Our findings demonstrate that the R3 inversion mutation patterns is (1) only seen with VIII:C activity levels of {le} 2.4%, (2) seen in 46% of families with severe hemophilia, (3) seen in 45% of hemophiliacs known to have inhibitors, (4) not correlated with sporadic or familial disease and (5) not in disequilibrium with the Bcl I or Taq I intron 18 or ST14 polymorphisms. Finally, in families positive for an inversion mutation, direct testing offers a highly accurate and less expensive alternative to DNA linkage analysis.

  2. Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study Úlcera perianastomótica após derivação gástrica em Y-de-Roux mesmo em uso de inibidor de bomba de prótons: estudo prospectivo multicêntrico

    Directory of Open Access Journals (Sweden)

    Arthur Belarmino Garrido Jr.

    2010-06-01

    Full Text Available CONTEXT: Causal factors of gastrojejunal ulcers after Roux-en-Y gastric bypass include peptic acid secretion from the gastric pouch. Esomeprazole is a potent inhibitor of acid secretion. OBJECTIVE: To assess the occurrence of dyspepsia and gastrojejunal ulcers within the first 2 months after Roux-en-Y gastric bypass during the use of esomeprazole. METHODS: One hundred eighteen morbid obese subjects were submitted to Roux-en-Y gastric bypass. Preoperative upper gastrointestinal tract endoscopy was negative for H. pylori. All subjects received esomeprazole for 60 days after surgery. RESULTS: Two weeks after surgery only 13 mild symptoms were reported. After 2 months, 17 also moderate complaints were registered. Endoscopy around the 60th day showed esophagitis in 10 (8.5%, hiatal hernia in 2 (1.7%, foreign body in the anastomotic line in 12 (10.2% and gastrojejunal ulcers was observed in 9 (7.6% subjects, 2 of which had a suture material or metallic staple granuloma in the gastrojejunostomy. Ten subjects took nonsteroidal anti-inflammatory drugs at least once during study, but none of them developed ulcer. None of the subjects with ulcer had dyspeptic symptoms. CONCLUSION: The incidence of ulcer in the gastrojejunal anastomosis within the first 2 months following Rouxen-Y gastric bypass under proton pump inhibitors is considerable. It was not related to the use of non-steroidal anti-inflammatory drugs, highlighting the possibility of ischemia and foreign body as causal factors. The ulcers were asymptomatic, and all post-surgical dyspeptic symptoms were moderate in severity.CONTEXTO: Sintomas dispépticos são comuns após derivação gástrica em Y-de-Roux. Podem decorrer de úlceras de boca anastomótica, cujos possíveis fatores causais incluem a secreção cloridropéptica da bolsa gástrica, isquemia, efeito de corpo estranho dos materiais de sutura e uso de antiinflamatórios não-esteróides. O esomeprazol é um redutor potente da secre

  3. Igor Zabel 14. VIII 1958 - 23. VII 2005

    Index Scriptorium Estoniae

    2005-01-01

    Igor Zabel oli Ida-Euroopa tuntumaid kunstiteoreetikuid ja kuraatoreid. Töötas 1986. aastast Ljubljana moodsa kunsti muuseumi kuraatorina. 9. VIII avatakse seal viimane I. Zabeli kureeritud näitus "Territories, Identities, Nets-Slovene Art 1995-2005"

  4. What history tells us VIII. The progressive construction of a ...

    Indian Academy of Sciences (India)

    2007-02-09

    Feb 9, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 2. What history tells us VIII. The progressive construction of a mechanism for prion diseases. Michel Morange. Series Volume 32 Issue 2 March 2007 pp 223-227. Fulltext. Click here to view fulltext PDF. Permanent link:

  5. The labour ward analgesic service at King Edward VIII Hospital ...

    African Journals Online (AJOL)

    dence of shivering9 and an improved sense of maternal well-being.lo. In summary, the study presented here shows that the analgesia service provided ro the labour ward at King. Edward VIII Hospital is at present grossly inadequate. In particular, a high proportion (76%) of mothers with a specific indication for epidural ...

  6. Functional regions in coagulation factor VIII explored by mass spectrometry

    NARCIS (Netherlands)

    Bloem, E.

    2013-01-01

    The molecular mechanisms behind the function of factor VIII (FVIII) have remained poorly understood. FVIII acts in the blood coagulation cascade as cofactor for activated factor IX (FIXa) in the membrane bound activated factor X generating (FXase) complex. A functional absence in FVIII leads to the

  7. Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A.

    Science.gov (United States)

    Dooriss, Kerry L; Denning, Gabriela; Gangadharan, Bagirath; Javazon, Elisabeth H; McCarty, David A; Spencer, H Trent; Doering, Christopher B

    2009-05-01

    Successful gene therapy of hemophilia A depends on the sustained expression of therapeutic levels of factor VIII (fVIII). Because of mRNA instability, interactions with resident endoplasmic reticulum (ER) chaperones, and the requirement for carbohydrate-facilitated transport from the ER to the Golgi apparatus, fVIII is expressed at much lower levels from mammalian cells than other proteins of similar size and complexity. A number of bioengineered forms of B domain-deleted (BDD) human fVIII have been generated and shown to have enhanced expression. Previously, we demonstrated that recombinant BDD porcine fVIII exhibits high-level expression due to specific sequence elements that increase biosynthesis via enhanced posttranslational transit through the secretory pathway. In the current study, high-expression recombinant fVIII constructs were compared directly in order to determine the relative expression of the various bioengineered fVIII transgenes. The data demonstrate that BDD porcine fVIII expression is superior to that of any of the human fVIII variant constructs tested. Mean fVIII expression of 18 units/10(6) cells/24 hr was observed from HEK-293 cells expressing a single copy of the porcine fVIII transgene, which was 36- to 225-fold greater than that of any human fVIII transgene tested. Furthermore, greater than 10-fold higher expression was observed in human cells transduced with BDD porcine fVIII versus BDD human fVIII-encoding lentiviral vectors, even at low proviral copy numbers, supporting its use over other human fVIII variants in future hemophilia A gene therapy clinical trials.

  8. Current peripheral bypass surgery: various clinical studies

    NARCIS (Netherlands)

    Slaa, Alexander te

    2011-01-01

    Substantial post-operative edema occurs in the majority of patients who undergo peripheral bypass surgery due to severe peripheral arterial disease (PAD). The pathophysiological mechanisms that underlay edema formation following peripheral bypass surgery include hyperemia, an increased capillary

  9. Secondary and College LD Bypass Strategies.

    Science.gov (United States)

    Mosby, Robert J.

    1981-01-01

    The author describes the Developmental By-Pass (DBP) Instructional technology for teaching secondary and college learning disabled (LD) students by allowing students to bypass ordering and organizational deficits. (SB)

  10. In situ bypass og diabetes

    DEFF Research Database (Denmark)

    Jensen, Leif Panduro; Schroeder, T V; Lorentzen, J E

    1993-01-01

    From 1986 through to 1990 a total of 483 in situ bypass procedures were performed in 444 patients. Preoperative risk-factors were equally distributed among diabetic (DM) and non-diabetic (NDM) patients, except for smoking habits (DM:48%, NDM:64%, p = 0.002) and cardiac disease (DM:45%, NDM:29%, p...... decreased survival rate was found in diabetics (p bypass technique very useful in the treatment of critical ischaemia of the lower limb in diabetic patients. The overall results in diabetic patients, whether insulin-dependent or not, were equal to those in non...

  11. Undiagnosed phaeochromocytoma following infrainguinal bypass surgery

    DEFF Research Database (Denmark)

    Levi, N; Schroeder, T V

    1998-01-01

    We present a rare case of undiagnosed phaeochromocytoma following infrainguinal bypass surgery. The patient, a 59-year-old lady, had a one year history of hypertension following a first femoro-tibial bypass and presented as a cardiorespiratory emergency in the admission room following her...... contralateral femoro-tibial bypass. The patient recovered after some days in intensive care despite a delayed diagnosis....

  12. Deep-water sediment bypass

    NARCIS (Netherlands)

    Stevenson, Christopher J.; Jackson, Christopher A L; Hodgson, David M.; Hubbard, Stephen M.; Eggenhuisen, Joris T.|info:eu-repo/dai/nl/322850274

    Submarine gravity flows are a key process for transporting large volumes of sediment from the continents to the deep sea. The location, volume, and character of the sediment bypassed by these flows dictates the areal extent and thickness of the associated deposits. Despite its importance, sediment

  13. Choroidal changes after cardiopulmonary bypass.

    Science.gov (United States)

    Pekel, G; Alur, I; Alihanoglu, Y I; Yagci, R; Emrecan, B

    2014-11-01

    Choroid, which is the vascular tissue responsible for blood supply to the outer parts of the retina, might be affected by hemodynamic events. We aimed to reveal choroidal thickness and ocular pulse amplitude changes after cardiopulmonary bypass in which gross hemodynamic alterations occur. Forty-two eyes of 42 patients who underwent heart surgery with cardiopulmonary bypass were examined in this prospective, cross-sectional case series. The spectral domain optical coherence tomography (Spectralis, Heidelberg, Germany) was used to analyze sub-foveal choroidal thickness. The ocular pulse amplitude, the surrogate of gross choroidal blood flow, was measured with the Pascal dynamic contour tonometer (Pascal DCT, Swiss Microtechnology AG, Port, Switzerland).. The intraocular pressure was also measured with this tonometer. The examinations were performed pre-operatively and post-operatively at the first week and first month. The mean age of the patients was 58.8 ± 12.4 years. The mean sub-foveal choroidal thickness and ocular pulse amplitude values did not change statistically significantly after the operations at the follow-up visits (p>0.05). Also, there were no important correlations between cardiopulmonary bypass time and mean sub-foveal choroidal thickness and ocular pulse amplitude changes at the post-operative first week (p>0.05). The intraocular pressure values were decreased markedly at the control visits (pcardiopulmonary bypass. © The Author(s) 2014.

  14. Potential role of a new PEGylated recombinant factor VIII for hemophilia A

    Directory of Open Access Journals (Sweden)

    Wynn TT

    2016-06-01

    Full Text Available Tung Thanh Wynn,1 Burak Gumuscu,2,3 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, 2Pediatric Hematology-Oncology, Bon Secours Health System, St. Mary’s Hospital, Richmond, VA, 3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Virginia, Charlottesville, VA, USA Abstract: Hemophilia A, a deficiency in the activity of coagulation factor (F VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing ­activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half-life of PEGylated factor is more prolonged when compared to non-PEGylated full-length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half

  15. The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

    Directory of Open Access Journals (Sweden)

    Caileen M Brison

    Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

  16. Hemophilia A gene therapy via intraosseous delivery of factor VIII-lentiviral vectors.

    Science.gov (United States)

    Miao, Carol H

    2016-01-01

    Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect. However, ex vivo HSC gene therapy requires pre-conditioning which is highly undesirable for hemophilia patients. The recently developed novel methodology of direct intraosseous (IO) delivery of LVs can efficiently transduce bone marrow cells, generating high levels of transgene expression in HSCs. IO delivery of E-F8-LV utilizing a ubiquitous EF1α promoter generated initially therapeutic levels of FVIII, however, robust anti-FVIII antibody responses ensued neutralized functional FVIII activity in the circulation. In contrast, a single IO delivery of G-FVIII-LV utilizing a megakaryocytic-specific GP1bα promoter achieved platelet-specific FVIII expression, leading to persistent, partial correction of HemA in treated animals. Most interestingly, comparable therapeutic benefit with G-F8-LV was obtained in HemA mice with pre-existing anti-FVIII inhibitors. Platelets is an ideal IO delivery vehicle since FVIII stored in α-granules of platelets is protected from high-titer anti-FVIII antibodies; and that even relatively small numbers of activated platelets that locally excrete FVIII may be sufficient to promote efficient clot formation during bleeding. Additionally, combination of pharmacological agents improved transduction of LVs and persistence of transduced cells and transgene expression. Overall, a single IO infusion of G-F8-LV can generate long-term stable

  17. Bypass materials in vascular surgery

    Directory of Open Access Journals (Sweden)

    Willich, Stephan N.

    2006-03-01

    Full Text Available Introduction: Arteriosclerotic changes can lead to circulatory disturbances in various areas of the human vascular system. In addition to pharmacological therapy and the management of risk factors (e. g. hypertension, diabetes, lipid metabolism disorders, and lifestyle, surgical interventions also play an important role in the treatment of arteriosclerosis. Long-segment arterial occlusions, in particular, can be treated successfully with bypass sur-gery. A number of different materials are available for this type of operation, such as autologous vein or pros-thetic grafts comprised of polytetrafluoroethylene (PTFE or Dacron®. Prosthetic materials are used especially in the treatment of peripheral artery disease, such as in aortoiliac or femoropopliteal bypass surgery. The present report will thus focus on this area in order to examine the effectiveness of different bypass materials. Among the efforts being made to refine the newly introduced DRG system in Germany, analysing the different bypass materials used in vascular surgery is particularly important. Indeed, in its current version the German DRG system does not distinguish between bypass materials in terms of reimbursement rates. Differences in cost structures are thus of especial interest to hospitals in their budget calculations, whereas both private and statutory health insurance funds are primarily interested in long-term results and their costs. Objectives: The goal of this HTA is to compare the different bypass materials used in vascular surgery in terms of their medical efficiency and cost-effectiveness, as well as with regard to their ethical, social and legal implications. In addition, this report aims to point out the areas in which further medical, epidemiological and health economic research is still needed. Methods: Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information

  18. Risk stratification for inhibitor development at first treatment for severe hemophilia A : a tool for clinical practice

    NARCIS (Netherlands)

    Ter Avest, P. C.; Mancuso, M. E.; Santagostino, E.; Yuste, V. J.; van den Berg, H. M.; van der Bom, J. G.

    2008-01-01

    Background: Replacement therapy in severe hemophilia A patients is complicated by formation of inhibitory antibodies against factor VIII (inhibitors) in around 25% of children. Management of bleeds and eradicating inhibitors is complicated, costly and not always successful. Objective: To develop a

  19. TT virus contaminates first-generation recombinant factor VIII concentrates.

    Science.gov (United States)

    Azzi, A; De Santis, R; Morfini, M; Zakrzewska, K; Musso, R; Santagostino, E; Castaman, G

    2001-10-15

    Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

  20. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

  1. Arrhythmias after coronary bypass surgery.

    OpenAIRE

    Ormerod, O J; McGregor, C G; Stone, D L; Wisbey, C; Petch, M C

    1984-01-01

    Ninety patients undergoing coronary bypass surgery were studied prospectively by bedside and subsequent ambulatory electrocardiographic monitoring to investigate the incidence, possible causes, and prevention of atrial fibrillation. Patients with good left ventricular function were divided randomly into a control group or groups treated with digoxin or propranolol. In the control group the incidence of atrial fibrillation was 27% and of significant ventricular extrasystoles 3%. Propranolol re...

  2. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. (Univ. of Vermont, Burlington (USA))

    1989-09-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  3. 40 CFR Appendix Viii to Part 600 - Fuel Economy Label Formats

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Fuel Economy Label Formats VIII... POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Pt. 600, App. VIII Appendix VIII to Part 600—Fuel Economy Label Formats EC01MY92.117 EC01MY92.118 EC01MY92.119 EC01MY92.120...

  4. Localization of collagen type VIII in normal and pathological human cornea

    OpenAIRE

    Zenklová, Kateřina

    2007-01-01

    The aim of this work was to localize collagen type VIII in different layers of the cornea and to compare it's localization in normal corneas with pathological corneas obtained from patients with Fuchs endothelial dystrophy, posterior polymorphous dystrophy or keratoconus.The only comercially available antibody did not proove sufficient specifiky for collagen type VIII. With use of the antibody 9H3 anti alCVIII was collagen VIII evidenced in the cornea. This antibody can be used for detection ...

  5. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.

    OpenAIRE

    Hill-Eubanks, D C; Parker, C G; Lollar, P

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as ...

  6. Cardiopulmonary bypass for pediatric cardiac surgery.

    Science.gov (United States)

    Hirata, Yasutaka

    2017-11-28

    The management of cardiopulmonary bypass for pediatric cardiac surgery is more challenging than that in adults due to the smaller size, immaturity, and complexity of the anatomy in children. Despite major improvements in cardiopulmonary bypass, there remain many subjects of debate. This review article discusses the physiology of cardiopulmonary bypass for pediatric and congenital heart surgery, including topics related to hemodilution, hypothermia, acid-base strategies, inflammatory response, and myocardial protection.

  7. Gastric bypass reduces fat intake and preference

    Science.gov (United States)

    Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R.; Spector, Alan C.; Olbers, Torsten; Lutz, Thomas A.

    2011-01-01

    Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation. PMID:21734019

  8. A comparison of haemodynamics between subcranial-intracranial bypass and the traditional extracranial-intracranial bypass.

    Science.gov (United States)

    Yu, Zaitao; Yang, Yang; Shi, Xiang'en; Qian, Hai; Liu, Fangjun

    2017-12-01

    Ischemic cerebrovascular diseases are traditionally treated using an extracranial-intracranial (EC-IC) bypass. The use of the internal maxillary artery (IMA) in the subcranial-intracranial (SC-IC) bypass was recently described as an alternative treatment. However, the haemodynamics of this new approach have not been defined. The haemodynamic parameters (flow volume [FV], internal diameter [ID], time-averaged mean velocity [TAM], pulsatility index [PI] and resistance index [RI]) of the IMA-radial artery graft (RAG)-middle cerebral artery (MCA) (n = 12) bypass and superficial temporal artery (STA)-MCA bypass (n = 18) were measured using intraoperative duplex ultrasonography and compared. The FV was 81.36 ± 30.41 (62.05-100.70) ml/min for the IMA-RAG-MCA bypass. This was significantly higher than that of the STA-MCA bypass (27.25 ± 9.32 (22.62-31.88) ml/min; P bypass were higher than in the STA-MCA bypass (P bypass and 94% for the STA-MCA bypass. The IMA-RAG-MCA bypass provides moderate to high blood flow to the revascularized territory and blood flow was higher by this method than the STA-MCA bypass.

  9. Factor VIII and transmissible spongiform encephalopathy: the case for safety.

    Science.gov (United States)

    Cervenakova, L; Brown, P; Hammond, D J; Lee, C A; Saenko, E L

    2002-03-01

    Haemophilia A is the most common inherited bleeding disorder, caused by a deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A is based on repeated infusions of plasma-derived FVIII concentrate or of recombinant FVIII, which may be exposed to plasma-derived material of human or animal origin used in its tissue culture production process. We review epidemiological and experimental studies relevant to blood infectivity in the transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and evaluate the hypothetical risk of TSE transmission through treatment with plasma-derived or recombinant FVIII.

  10. PENERAPAN METODE PENEMUAN TERBIMBING DI KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Toni Hidayat

    2017-08-01

    Full Text Available This study was a classroom action research which aims to investigate how the implementation of guided discovery learning can improve students’ activeness and attainment in the class VIII of Laboraturium UM Senior High School Malang city. The study subject was Class VIII that consists of 36 students, year 2016/2017. This study consisted of two cycles, and the data was collected from the result of the final test, observation, and interview. Based on the research of cycle I, the students’ activeness with mean scores of the meeting I, II, III was 78.88%, 79%, 86.6% respectively. The students’ activeness on cycle II, the mean scores of analyst meeting V and VI were 89.22% and 92.24% respectively. The result of Mathematics learning was increased, it is shown on the test mean of the cycle I that was achieved by 36 students with the percentage of successful learning 83 %. On the cycle test II, the average of 36 gained 82 (score with 7.2 increased from the score mean of the cycle I and with classical mastery learning cycle II 88.88%. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK yang bertujuan untuk mengetahui bagaimana penerapan metode penemuan terbimbing yang dapat meningkatan keaktifan dan hasil belajar siswa kelas VIII SMP Laboratorium UM Kota Malang. Subjek penelitian ini ialah siswa kelas VIII yang berjumlah 36 siswa tahun pelajaran 2016/2017. Penelitian ini terdiri atas dua siklus dan data dikumpulkan dari hasil tes akhir tindakan, observasi, dan wawancara. Berdasarakan hasil penelitian pada siklus I, keaktifan siswa siswa dengan skor rata-rata pertemuan I, II, III adalah 78,88% 79,%, dan 86,6%. Aktivitas siswa pada siklus II, rata-rata skor pengamat pertemuan V dan VI berturut-turut 89,22 % dan 92,24%. Hasil belajar matematika siswa meningkat, hal ini terlihat bahwa rata-rata tes siklus I yang diperoleh 36 siswa sebesar 74,8 dengan presentase keberhasilan belajar 83,33%. Pada tes siklus II rata-rata nilai menjadi 82 dengan

  11. A rare combination: Combined factor V and factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    Başak Ünver Koluman

    2014-06-01

    Full Text Available Combined factor V (FV and factor VIII (FVIII deficiency is a rare factor deficiency with mild-moderate hemorrhage. It is an autosomal recessive coagulation disorder . Prolonged prothrombin time and partial thromboplastic time is characteristic, platelet count remains in normal ranges. The main stay of treatment is to control the hemorrhage. Fresh frozen plasma, desmopressin, specific FVIII concentrates (plasma- derived or recombinant may be used. Being very rare in the general population, we present a case with a combined FV and FVIII deficiency. J Clin Exp Invest 2014; 5 (2: 323-325

  12. Coronary bypass grafting without use of cardiopulmonary bypass for dextrocardia.

    Science.gov (United States)

    Mujanovic, Emir; Bergsland, Jacob; Tursic, Ademir; Stanimirovic-Mujanovic, Sanja; Kabil, Emir

    2011-01-01

    Dextrocardia is a condition in which the heart is pointed toward the right side of the chest instead of normally pointing to the left. The rate of atherosclerotic heart disease in subjects with this condition is similar to that of the general population. We present a patient with situs inversus totalis with dextrocardia who underwent coronary artery bypass grafting without use of cardiopulmonary bypass (OPCAB). A 74-year-old man who was known to have dextrocardia with situs inversus was admitted to the hospital because of angina. Coronary angiography was performed and showed ostial occlusion of the left anterior descendng artery (LAD) unsuitable for percutaneous coronary interventions but collatereralised from the right coronary artery. Patient underwent OPCAB under general anestesia. Right internal mammary artery was anastomosed to LAD on the beating heart with the surgeon standing on the right side of the patient. The patient's post-operative course was uneventful, and he was discharged on the 6th postoperative day in good condition. Performing OPCAB surgery is not technically more demanding, and present no unusual challenge on patients with dextrocardia.

  13. Coronary Artery Bypass in Octogenarians

    Directory of Open Access Journals (Sweden)

    Chen-Yen Chien

    2012-09-01

    Full Text Available Prevalence of coronary artery disease (CAD has increased with the expansion of life span among the elderly population in the world. Hence, the issue of the coronary artery bypass in octogenarians has attracted more attention. Recent literature about the topic revealed nearly the same excellent results as those in the younger population under the newly developed operative techniques and improving concept in perioperative management and postoperative care. In this article, we review the current status of the procedure that was thought to be dangerous in the earlier era, including its risk factors, result, and benefit.

  14. Enhancement of pig embryonic implants in factor VIII KO mice: a novel role for the coagulation cascade in organ size control.

    Directory of Open Access Journals (Sweden)

    Anna Aronovich

    Full Text Available Very little is known about the mechanisms that contribute to organ size differences between species. In the present study, we used a mouse model of embryonic pig tissue implantation to define the role of host Factor VIII in controlling the final size attained by the implant. We show here that pig embryonic spleen, pancreas, and liver all grow to an increased size in mice that are deficient in the Factor VIII clotting cascade. Similar results were obtained using the transplantation model after treatment with the low molecular weight heparin derivative Clexane which markedly enhanced transplant size. Likewise, enhanced size was found upon treatment with the direct thrombin inhibitor Dabigatran, suggesting that organ size regulation might be mediated by thrombin, downstream of Factor VIII. Considering that thrombin was shown to mediate various functions unrelated to blood clotting, either directly by cleavage of protease-activated receptors (PARs or indirectly by cleaving osteopontin (OPN on stroma cells, the role of PAR1 and PAR4 antagonists as well as treatment with cleaved form of OPN (tcOPN were tested. While the former was not found to have an impact on overgrowth of embryonic pig spleen implants, marked reduction of size was noted upon treatment with the (tcOPN. Collectively, our surprising set of observations suggests that factors of the coagulation cascade have a novel role in organ size control.

  15. Analysis of risk factors for occlusions of a synthetic femoropopliteal bypass graft

    Directory of Open Access Journals (Sweden)

    Mirković Nikola

    2015-01-01

    Full Text Available Background/Aim. Femoropopliteal bypass is a revascularization technique of lower extremities with excellent outcome. The great saphenous vein is the best graft material, but if it is not adequate or has been removed, synthetic grafts are an useful alternative. Graft occlusion is the most significant complication with the most serious consequences. The aim of this study was to analyse predictive factors for the synthetic femoropopliteal bypass occlusions. Methods. This retrospective case-control study included all patients who underwent synthetic femoropopliteal bypass due to peripheral arterial occlusive disease at the Vascular Surgery Center, Clinical Center of Kragujevac, Serbia, from 2007 to 2013. The cases group were the patients with femoropopliteal graft occlusion (n = 44, with the control group consisted of the patients without such an outcome (n = 88. Results. Significant effects to occlusion were: concomitant cardiovascular disease (adjustedOR 27.05; 95% CI 4.74; 154.35, a type of femoropopliteal bypass (adjustedOR 16.50; 95% CI 4.05; 67.24, previous vascular intervention (adjustedOR 4.67; 95% CI 1.20; 18.14, clinical stage of the disease (adjustedOR 3.73; 95% CI 1.94; 7.18, administration of postoperative oral anticoagulant therapy (adjustedOR 0.05; 95% CI 0.01; 0.23 and the use of angiotensin converting enzyme inhibitors (adjustedOR 0.14; 95% CI 0.03; 0.70. A significant synergism was shown for the following combinations of the observed risk factors: type of femoropopliteal bypass and cardiovascular disease, type of femoropopliteal bypass and previous vascular intervention, previous vascular intervention and cardiovascular disease, previous vascular intervention and beta blockers, cardiovascular disease and diabetes, type of femoropopliteal bypass and antiaggregant therapy, clinical stage of disease and cardiovascular disease, previous vascular intervention and antiaggregant therapy. Conclusion. Concomitant cardiovascular disease

  16. Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice.

    Science.gov (United States)

    Miao, Carol H; Ye, Peiqing; Thompson, Arthur R; Rawlings, David J; Ochs, Hans D

    2006-07-01

    A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

  17. Strategies for optimisation of paediatric cardiopulmonary bypass

    NARCIS (Netherlands)

    Somer, Filip Maria Jan Jozef De

    2003-01-01

    The aim of this thesis is to address different aspects of paediatric cardiopulmonary bypass in detail and to propose modifications in order to reduce cardiopulmonary bypass related morbidity and by doing so, improve patient outcome. We will focus on four major items: (1) vascular access, (2) mass

  18. Cephalic veins in coronary artery bypass surgery

    DEFF Research Database (Denmark)

    Licht, P; Jakobsen, Erik; Lerbjerg, G

    1996-01-01

    Various alternative conduits for aortocoronary bypass grafting have been suggested when the saphenous vein quality is inadequate. During a 10-year period we have used the cephalic vein in 39 patients. Eighteen entered an angiographic follow-up study. A total of 31 arm vein grafts were used with 43...... bypass operations....

  19. Multimodality imaging of coronary artery bypass grafts

    NARCIS (Netherlands)

    Salm, Liesbeth Pauline

    2006-01-01

    This thesis describes multiple imaging modalities to examine coronary artery bypass grafts, and the research which was performed to further develop noninvasive imaging techniques to detect stenoses in native coronary arteries and bypass grafts in patients who experienced recurrent chest pain after

  20. Epicardial ultrasound in coronary artery bypass surgery

    NARCIS (Netherlands)

    Budde, R.P.J.

    2005-01-01

    Chapter 1 Coronary artery bypass surgery (CABG) is traditionally performed via a median sternotomy approach on cardiopulmonary bypass (arrested heart). Since the mid 1990ties, beating heart, minimally invasive and even totally endoscopic CABG are (re)explored. In all approaches to CABG, the

  1. Evidence for the formation of sodium hassate(VIII)

    Energy Technology Data Exchange (ETDEWEB)

    Zweidorf, A. von [Inst. fuer Kernchemie, Johannes Gutenberg-Univ. Mainz, Mainz (Germany); Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Angert, R.; Bruechle, W.; Buerger, S.; Eberhardt, K.; Eichler, R.; Hummrich, H.; Jaeger, E.; Kling, H.O.; Kratz, J.V.; Kuczewski, B.; Langrock, G.; Mendel, M.; Rieth, U.; Schaedel, M.; Schausten, B.; Schimpf, E.; Thoerle, P.; Trautmann, N.; Tsukada, K.; Wiehl, N.; Wirth, G.

    2004-07-01

    Hassium, element 108, was produced in the fusion reaction between {sup 26}Mg and {sup 248}Cm. The hassium recoils were oxidized in-situ to a highly volatile oxide, presumably HsO{sub 4}, and were transported in a mixture of He and O{sub 2} to a deposition and detection system. The latter consisted of 16 silicon PIN-photodiodes facing a layer of NaOH, which served, in the presence of a certain partial pressure of water in the transport gas, as reactive surface for the deposition of the volatile tetroxides. Six correlated {alpha}-decay chains of Hs were detected in the first 5 detectors centred around detection position 3. In analogy to OsO{sub 4}, which forms Na{sub 2}[OsO{sub 4}(OH){sub 2}], an osmate(VIII), with aqueous NaOH, HsO{sub 4} presumably was deposited as Na{sub 2}[HsO{sub 4}(OH){sub 2}], a hassate(VIII). (orig.)

  2. Aristóteles y las series causales infinitas en Física VII y VIII

    Directory of Open Access Journals (Sweden)

    Alberto Ross

    2013-11-01

    Full Text Available The aim of this paper is to show that we have at least two different arguments that prove the First Motor's existence. Even though there are coincidences between Physics VII 1 and VIII 5, their arguments are not identical. Physics VII argue the impossibility of an infinite movement in a finite time and VIII 5 the necessity of a "principal" cause.

  3. Effectiveness of Mind Mapping in English Teaching among VIII Standard Students

    Science.gov (United States)

    Hallen, D.; Sangeetha, N.

    2015-01-01

    The aim of the study is to find out the effectiveness of mind mapping technique over conventional method in teaching English at high school level (VIII), in terms of Control and Experimental group. The sample of the study comprised, 60 VIII Standard students in Tiruchendur Taluk. Mind Maps and Achievement Test (Pretest & Posttest) were…

  4. 40 CFR Appendix Viii to Part 85 - Vehicle and Engine Parameters and Specifications

    Science.gov (United States)

    2010-07-01

    .... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system.... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system... Specifications VIII Appendix VIII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  5. 40 CFR Appendix Viii to Part 266 - Organic Compounds for Which Residues Must Be Analyzed

    Science.gov (United States)

    2010-07-01

    ... AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VIII Appendix VIII to Part 266... residues collected from areas downstream of the combustion chamber (e.g., ductwork, boiler tubes, heat...

  6. Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow.

    Science.gov (United States)

    Swieringa, Frauke; Kuijpers, Marijke J E; Lamers, Moniek M E; van der Meijden, Paola E J; Heemskerk, Johan W M

    2015-06-01

    The importance of factor Xa generation in thrombus formation has not been studied extensively so far. Here, we used mice deficient in either factor VIII or factor IX to determine the role of platelet-stimulated tenase activity in the formation of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in factor VIII or IX markedly suppressed thrombus growth, fibrin formation and platelet procoagulant activity (phosphatidylserine exposure). In either case, residual fibrin formation was eliminated in the absence of tissue factor. Effects of factor deficiencies were antagonized by supplementation of the missing coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine-exposing platelets bound (activated) factor IX and factor X, whereas factor VIII preferentially co-localized at sites of von Willebrand factor binding. Furthermore, proteolytic activity of the generated activated factor X and thrombin was confined to the sites of phosphatidylserine exposure. With blood from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was greatly delayed and reduced, even in the presence of high concentrations of tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human blood, suppressed both thrombin and fibrin formation. Together, these data point to a potent enforcement loop in thrombus formation due to factor X activation, subsequent thrombin and fibrin generation, causing activated factor X-mediated stimulation of platelet phosphatidylserine exposure. This implies that the factor VIII/factor IX-dependent stimulation of platelet procoagulant activity is a limiting factor for fibrin formation under flow conditions, even at high tissue factor concentrations. Copyright© Ferrata Storti Foundation.

  7. Endogenous factor VIII synthesis from the intron 22-inverted F8 locus may modulate the immunogenicity of replacement therapy for hemophilia A.

    Science.gov (United States)

    Pandey, Gouri Shankar; Yanover, Chen; Miller-Jenkins, Lisa M; Garfield, Susan; Cole, Shelley A; Curran, Joanne E; Moses, Eric K; Rydz, Natalia; Simhadri, Vijaya; Kimchi-Sarfaty, Chava; Lillicrap, David; Viel, Kevin R; Przytycka, Teresa M; Pierce, Glenn F; Howard, Tom E; Sauna, Zuben E

    2013-10-01

    Neutralizing antibodies (inhibitors) to replacement factor VIII (FVIII, either plasma derived or recombinant) impair the effective management of hemophilia A. Individuals with hemophilia A due to major deletions of the FVIII gene (F8) lack antigenically cross-reactive material in their plasma ("CRM-negative"), and the prevalence of inhibitors in these individuals may be as high as 90%. Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-positive, and their overall prevalence of inhibitors is hemophilia A) have been grouped with the former on the basis of their genetic defect and CRM-negative status. However, only ∼20% of these individuals develop inhibitors. Here we demonstrate that the levels of F8 mRNA and intracellular FVIII protein in B lymphoblastoid cells and liver biopsies from individuals with the intron 22 inversion are comparable to those in healthy controls. These results support the hypothesis that most individuals with the intron 22 inversion are tolerized to FVIII and thus do not develop inhibitors. Furthermore, we developed a new pharmacogenetic algorithm that permits the stratification of inhibitor risk for individuals and subpopulations by predicting the immunogenicity of replacement FVIII using, as input, the number of putative T cell epitopes in the infused protein and the competence of major histocompatibility complex class II molecules to present such epitopes. This algorithm showed statistically significant accuracy in predicting the presence of inhibitors in 25 unrelated individuals with the intron 22 inversion.

  8. Coronary arteries bypass grafting stenosis

    Directory of Open Access Journals (Sweden)

    Mahmoud Ebrahimi

    2014-12-01

    Full Text Available Coronary artery disease (CAD is a major global problem. In addition, it is higher risk of mortality for women more than men are when develop in female gender Atherosclerotic plaques consist of deposits of fatty material in the tunica intima. The role of inflammatory process in CAD has been known from 1980’s. Several studies investigated the innate immunity and adaptive immunity roles in atherosclerosis and they concluded that it plays a key role in atherosclerosis. Coronary artery bypass grafting (CABG is a widely used method for the treatment of CAD. Based on the literature, CABG is the most common surgical operation done worldwide. In During the first 10 years after CABG, up to 50% of saphenous grafts will occlude. Graft restenosis is beginning with acute thrombosis, intima hyperplasia, and plaque formation. In this review, some molecular pathways of graft failure and restenosis such as apoptosis and nuclear factor kappa B (NF-ĸB are described.

  9. Cardiopulmonary Bypass and Oxidative Stress

    Science.gov (United States)

    Zakkar, Mustafa; Guida, Gustavo; Suleiman, M-Saadeh; Angelini, Gianni D.

    2015-01-01

    The development of the cardiopulmonary bypass (CPB) revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress. PMID:25722792

  10. Capacity analysis of a bypass of roundabouts

    Science.gov (United States)

    Sedlačik, Ivan; Slabý, Petr

    2017-09-01

    The capacity of the roads network mainly depends on the capacity of its nodal points - intersections. A connecting branch or a bypass is a lane or lanes inserted between two adjacent branches of a roundabout, providing redirection of vehicles, that would otherwise burden a circular lane. A bypass effect to the capacity of roundabouts, but also other types of level intersections, is undeniable. A connecting branch increases the total capacity of an intersection that takes a part of vehicles performing a manoeuver of the first right turn completely out of an intersection area. Redirecting vehicles reduces delay times at intersections and reduces queues at the entrance to an intersection. Bypasses improve the quality of transport. Limiting for the capacity of bypasses is the point of disconnection from the entrance into the roundabout and the connection point into the exit from the roundabout. Central parts of the bypasses have minimal effects on the capacity. The length of a bypass has to match with the maximum length of a queue of waiting vehicles at a given intensity level. The article deals with analysis of the bypass capacity at the roundabouts.

  11. Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral immune response in factor VIII-deficient mice.

    Science.gov (United States)

    Meslier, Yann; André, Sébastien; Teyssandier, Maud; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2010-12-01

    Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or used in prophylaxis induces inhibitory anti-FVIII immunoglobulin G (IgG) in some patients with haemophilia A. Therapeutic strategies to prevent the onset of the deleterious anti-FVIII immune response are still lacking. Maternal IgG is transferred to the offspring during fetal and neonatal life. While protecting the offspring from bacterial and viral infections, maternal IgG may alter the repertoires of T and B lymphocytes, and may impair vaccination in early infancy. Using haemophilic mice, we demonstrate that the transfer of maternal anti-FVIII IgG modulates the onset of anti-FVIII inhibitory IgG in early adulthood. The protective effect is reproduced upon reconstitution of naive mice with anti-FVIII IgG, suggesting that the reduced ability to mount an anti-FVIII immune response is the result of an interference between circulating anti-FVIII IgG and the administered FVIII rather than to a profound remodelling of lymphocyte repertoires occurring during the ontogeny of the immune system. © 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd.

  12. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b) Classification...

  13. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class II...

  14. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is... through the cardiopulmonary bypass circuit. (b) Classification. Class II (performance standards). ...

  15. 21 CFR 870.4200 - Cardiopulmonary bypass accessory equipment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass accessory equipment. 870... Cardiopulmonary bypass accessory equipment. (a) Identification. Cardiopulmonary bypass accessory equipment is a device that has no contact with blood and that is used in the cardiopulmonary bypass circuit to support...

  16. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass cardiotomy return sucker... Cardiopulmonary bypass cardiotomy return sucker. (a) Identification. A cardiopulmonary bypass cardiotomy return... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class II...

  17. 21 CFR 870.4350 - Cardiopulmonary bypass oxygenator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass oxygenator. 870.4350... bypass oxygenator. (a) Identification. A cardiopulmonary bypass oxygenator is a device used to exchange... the FDA guidance document entitled “Guidance for Cardiopulmonary Bypass Oxygenators 510(k) Submissions...

  18. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing...

  19. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow... device is placed in a cardiopulmonary bypass circuit downstream from the oxygenator. (b) Classification...

  20. Agnostic Stacking of Intergalactic Doublet Absorption: Measuring the Ne VIII Population

    Science.gov (United States)

    Frank, Stephan; Pieri, Matthew M.; Mathur, Smita; Danforth, Charles W.; Michael Shull, J.

    2018-02-01

    We present a blind search for doublet intergalactic metal absorption with a method dubbed `agnostic stacking'. Using a forward-modelling framework we combine this with direct detections in the literature to measure the overall metal population. We apply this novel approach to the search for Ne VIII absorption in a set of 26 high-quality COS spectra. We probe to an unprecedented low limit of log N>12.3 at 0.47≤z ≤1.34 over a pathlength Δz = 7.36. This method selects apparent absorption without requiring knowledge of its source. Stacking this mixed population dilutes doublet features in composite spectra in a deterministic manner, allowing us to measure the proportion corresponding to Ne VIII absorption. We stack potential Ne VIII absorption in two regimes: absorption too weak to be significant in direct line studies (12.3 13.7). We do not detect Ne VIII absorption in either regime. Combining our measurements with direct detections, we find that the Ne VIII population is reproduced with a power law column density distribution function with slope β = -1.86+0.18-0.26 and normalisation log f_{13.7} = -13.99+0.20-0.23, leading to an incidence rate of strong Ne VIII absorbers dn/dz =1.38+0.97-0.82. We infer a cosmic mass density for Ne VIII gas with 12.3 constituting 4% of the total baryonic mass.

  1. Coronary Bypass Surgery in a 105-Year-Old Patient with Cardiopulmonary Bypass

    Directory of Open Access Journals (Sweden)

    Temucin Noyan Ogus

    2010-01-01

    Full Text Available Coronary artery bypass grafting is one of the routine daily surgical procedures in the current era. Parallel to the increasing life expectancy, cardiac surgery is commonly performed in octogenarians. However, literature consists of only seldom reports of coronary artery bypass grafting in patients above 90 years of age. In this report, we present our management strategy in a 105-year-old patient who underwent coronary artery bypass grafting at our institution.

  2. Non-genetic risk factors in haemophilia A inhibitor management

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers both......, and explanations for this association are being investigated. A potential explanation is the danger signal effect, where the immune response is activated by endogenous or exogenous danger or damage signals present at the time and site of FVIII administration. The danger theory explains how alarm signals from...

  3. Impact of inhibitors on hemophilia A mortality in the United States.

    Science.gov (United States)

    Walsh, Christopher E; Soucie, J Michael; Miller, Connie H

    2015-05-01

    The previously published mortality studies are limited in hemophilia populations but suggest that there is no increased risk of mortality in factor VIII inhibitor patients. This retrospective study analyzed surveillance data collected on 7,386 males with severe hemophilia A over a 13-year period to assess the association between a current inhibitor and death. During the study period, 432 participants died, among whom 48 were patients with an inhibitor. Clinical characteristics most strongly associated with death were increased number of reported bleeds, signs of liver disease, infection with either HIV or HCV, and the presence of inhibitor. Patients who underwent successful tolerization were not considered inhibitor patients in our analysis. In a multivariable analysis, the odds of death were 70% higher among patients with a current inhibitor compared to those without an inhibitor (P hemophilia A and a current inhibitor are at increased risk of death. © 2015 Wiley Periodicals, Inc.

  4. Exhaust gas bypass valve control for thermoelectric generator

    Science.gov (United States)

    Reynolds, Michael G; Yang, Jihui; Meisner, Greogry P.; Stabler, Francis R.; De Bock, Hendrik Pieter Jacobus; Anderson, Todd Alan

    2012-09-04

    A method of controlling engine exhaust flow through at least one of an exhaust bypass and a thermoelectric device via a bypass valve is provided. The method includes: determining a mass flow of exhaust exiting an engine; determining a desired exhaust pressure based on the mass flow of exhaust; comparing the desired exhaust pressure to a determined exhaust pressure; and determining a bypass valve control value based on the comparing, wherein the bypass valve control value is used to control the bypass valve.

  5. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie

    2016-01-01

    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...... performance, and in relevant disease cohorts. The developed ELISA was applied for the assessment of type VIII collagen in serum from patients diagnosed with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and various cancers. Results The C8-C ELISA was technically stable...

  6. Environmental impact case study : Martinsville bypass.

    Science.gov (United States)

    1971-01-01

    At the request of the Environmental Quality Division, the Environmental and Economics Section of the Virginia Highway Research Council conducted an environmental impact study of the proposed Route 220 bypass around Martinsville. This evaluation of th...

  7. Bypass diode for a solar cell

    Science.gov (United States)

    Rim, Seung Bum [Palo Alto, CA; Kim, Taeseok [San Jose, CA; Smith, David D [Campbell, CA; Cousins, Peter J [Menlo Park, CA

    2012-03-13

    Bypass diodes for solar cells are described. In one embodiment, a bypass diode for a solar cell includes a substrate of the solar cell. A first conductive region is disposed above the substrate, the first conductive region of a first conductivity type. A second conductive region is disposed on the first conductive region, the second conductive region of a second conductivity type opposite the first conductivity type.

  8. [Plasma ionized magnesium concentration following cardiopulmonary bypass].

    Science.gov (United States)

    Amaya, Fumimasa; Fukui, Michihiko; Tsuruta, Hiroshi; Kooguchi, Kunihiko; Shimosato, Goshun

    2002-06-01

    We performed a retrospective study to analyze plasma ionized magnesium concentration following cardiopulmonary bypass. Severe decrease of ionized magnesium concentration associated with frequent abnormal ECG sign was found in a patient with magnesium-free cardioplegia. Cardioplegia containing 16 mmol.l-1 of magnesium ion maintained ionized magnesium concentration within normal ranges without postoperative magnesium loading. Use of cardioplegia containing magnesium or adequate magnesium supplement is thought to be essential for patients receiving cardiopulmonary bypass.

  9. Monsanto may bypass NIH in microbe test.

    Science.gov (United States)

    Sun, Marjorie

    1985-01-11

    The Monsanto Company is planning to ask the Environmental Protection Agency for clearance to field test a genetically engineered microbial pesticide, bypassing the traditional approval process of the National Institutes of Health. Although only federally funded institutions are required to obtain NIH approval for genetic engineering tests, Monsanto is the first company to bypass the NIH regulatory process, which has become mired in a lawsuit brought by Jeremy Rifkin.

  10. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

    Science.gov (United States)

    Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

    2012-01-01

    Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

  11. [Simplified laparoscopic gastric bypass. Initial experience].

    Science.gov (United States)

    Hernández-Miguelena, Luis; Maldonado-Vázquez, Angélica; Cortes-Romano, Pablo; Ríos-Cruz, Daniel; Marín-Domínguez, Raúl; Castillo-González, Armando

    2014-01-01

    Obesity surgery includes various gastrointestinal procedures. Roux-en-Y gastric bypass is the prototype of mixed procedures being the most practiced worldwide. A similar and novel technique has been adopted by Dr. Almino Cardoso Ramos and Dr. Manoel Galvao called "simplified bypass," which has been accepted due to the greater ease and very similar results to the conventional technique. The aim of this study is to describe the results of the simplified gastric bypass for treatment of morbid obesity in our institution. We performed a descriptive, retrospective study of all patients undergoing simplified gastric bypass from January 2008 to July 2012 in the obesity clinic of a private hospital in Mexico City. A total of 90 patients diagnosed with morbid obesity underwent simplified gastric bypass. Complications occurred in 10% of patients; these were more frequent bleeding and internal hernia. Mortality in the study period was 0%. The average weight loss at 12 months was 72.7%. Simplified gastric bypass surgery is safe with good mid-term results and a loss of adequate weight in 71% of cases.

  12. Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; Dunn, Amy L.; Tarantino, Michael D.; Brettler, Doreen B.; Barrett, John C.; Miller, Connie H.

    2015-01-01

    Summary Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing. PMID:25354263

  13. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  14. Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

    Science.gov (United States)

    Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

    2017-01-01

    Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of

  15. Historia y globalización. VIII Conversaciones Internacionales de Historia [Reseña

    OpenAIRE

    Olábarri-Gortázar, I. (Ignacio)

    2013-01-01

    Reseña de Francisco Javier Caspistegui (ed.), Historia y globalización. VIII Conversaciones Internacionales de Historia. Universidad de Navarra. Pamplona, 7-9 de octubre de 2010, Pamplona, EUNSA, 2012. 318 pp. ISBN: 9788431328801.

  16. Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A.

    Science.gov (United States)

    Wang, Xuefeng; Shin, Simon C; Chiang, Andy F J; Khan, Iram; Pan, Dao; Rawlings, David J; Miao, Carol H

    2015-04-01

    Intraosseous (IO) infusion of lentiviral vectors (LVs) for in situ gene transfer into bone marrow may avoid specific challenges posed by ex vivo gene delivery, including, in particular, the requirement of preconditioning. We utilized IO delivery of LVs encoding a GFP or factor VIII (FVIII) transgene directed by ubiquitous promoters (a MND or EF-1α-short element; M-GFP-LV, E-F8-LV) or a platelet-specific, glycoprotein-1bα promoter (G-GFP-LV, G-F8-LV). A single IO infusion of M-GFP-LV or G-GFP-LV achieved long-term and efficient GFP expression in Lineage(-)Sca1(+)c-Kit(+) hematopoietic stem cells and platelets, respectively. While E-F8-LV produced initially high-level FVIII expression, robust anti-FVIII immune responses eliminated functional FVIII in circulation. In contrast, IO delivery of G-F8-LV achieved long-term platelet-specific expression of FVIII, resulting in partial correction of hemophilia A. Furthermore, similar clinical benefit with G-F8-LV was achieved in animals with pre-existing anti-FVIII inhibitors. These findings further support platelets as an ideal FVIII delivery vehicle, as FVIII, stored in α-granules, is protected from neutralizing antibodies and, during bleeding, activated platelets locally excrete FVIII to promote clot formation. Overall, a single IO infusion of G-F8-LV was sufficient to correct hemophilia phenotype for long term, indicating that this approach may provide an effective means to permanently treat FVIII deficiency.

  17. Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII.

    Science.gov (United States)

    O'Sullivan, Jamie M; Jenkins, P Vince; Rawley, Orla; Gegenbauer, Kristina; Chion, Alain; Lavin, Michelle; Byrne, Barry; O'Kennedy, Richard; Preston, Roger J S; Brophy, Teresa M; O'Donnell, James S

    2016-05-01

    Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII. Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK-rFVIII compared with CHO-rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD-FVIII was markedly reduced compared with full-length rFVIII. We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII. © 2016 American Heart Association, Inc.

  18. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII.

    Science.gov (United States)

    Shah, A; Delesen, H; Garger, S; Lalezari, S

    2015-11-01

    BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. The LEOPOLD trials enrolled patients with severe haemophilia A aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups. © 2015 John Wiley & Sons Ltd.

  19. A Cranial Trauma was the Cause of Death of Charles VIII of France (1470-1498).

    Science.gov (United States)

    Markatos, Konstantinos; Karamanou, Marianna; Arkoudi, Konstantina; Konstantinidi, Apostolia; Androutsos, Georgios

    2017-09-01

    This article summarizes the reign, life and death, of Charles VIII of France. Also we intend to investigate current views on his cause of death, contradictions and opinions of his biographers. Poisoning, disease, and injury are the possible causes of his death but, according to the literature, cranial trauma was the most probable cause of death of the King Charles VIII of France. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. PENGARUH KONSELING KELOMPOK TERHADAP KONFORMITAS SISWI KELAS VIII SMPIT BINA AMAL SEMARANG

    OpenAIRE

    sudyastuti sudyastuti; heru mugiarso

    2017-01-01

    This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the ps...

  1. Type VIII collagen has a restricted distribution in specialized extracellular matrices

    OpenAIRE

    1988-01-01

    A pepsin-resistant triple helical domain (chain 50,000 Mr) of type VIII collagen was isolated from bovine corneal Descemet's membrane and used as an immunogen for the production of mAbs. An antibody was selected for biochemical and tissue immunofluorescence studies which reacted both with Descemet's membrane and with type VIII collagen 50,000-Mr polypeptides by competition ELISA and immunoblotting. This antibody exhibited no crossreactivity with collagen types I-VI by competition ELISA. The m...

  2. Implications of an updated ultraviolet background for the ionization mechanisms of intervening Ne VIII absorbers

    Science.gov (United States)

    Hussain, Tanvir; Khaire, Vikram; Srianand, Raghunathan; Muzahid, Sowgat; Pathak, Amit

    2017-04-01

    Ne VIII absorbers seen in QSO spectra are useful tracers of warm ionized gas, when collisional ionization is the dominant ionization process. While photoionization by the ultraviolet background (UVB) is a viable option, it tends to predict large line-of-sight thickness for the absorbing gas. Here, we study the implications of the recently updated UVB at low z to understand the ionization mechanisms of intervening Ne VIII absorbers. With the updated UVB, one typically needs higher density and metallicity to reproduce the observed ionic column densities under photoionization. Both reduce the inferred line-of-sight thicknesses of the absorbers. We find a critical density of ≥5 × 10-5 cm-3 above which the observed N({Ne VIII})/N({O VI}) can be reproduced by pure collisional processes. If the gas is of near solar metallicity (as measured for the low ions) then the cooling time-scales will be small (inferred low ion metallicity is near solar or supersolar. If we assume the Ne VIII phase to have similar metallicities then photoionization can reproduce the observed N({Ne VIII})/N({O VI}) without the line-of-sight thickness being unreasonably large and avoids cooling issues related to the collisional ionization at these metallicities. However, the indication of broad Lyα absorption in a couple of systems, if true, suggests that the Ne VIII phase is distinct from the low ion phase having much lower metallicity.

  3. Functional mapping of factor VIII C2 domain.

    Science.gov (United States)

    Pellequer, Jean-Luc; Chen, Shu-wen W; Saboulard, Didier; Delcourt, Marc; Négrier, Claude; Plantier, Jean-Luc

    2011-07-01

    The factor VIII (FVIII) is a cofactor of the coagulation cascade. The FVIII C2 domain is a critical domain that participates in the interactions with the von Willebrand factor and the phospholipidic surfaces. To assess the importance of each residue of this domain in the maintenance of the structure and the function of FVIII, a number (n=139) of mutants were generated by substituting the original residues, from Ser2173 to Gly2325, by an alanine. Mutants were built within a complete B domain-deleted FVIII and expressed in COS-1 cells. Mutant antigen levels and procoagulant activities were measured. Two in silico analyses, a sliding average procedure and an analysis of the mutation energy cost were conducted in parallel on the FVIII structure. Both results were in agreement with the functional data, and illustrated the benefit of using such strategies prior to targeting specific residues in the aim of generating active recombinant molecules. The functional assays identify the residues that are important to maintaining the structure of the C2 domain, mainly those forming β-sheet, and those that can afford substitution, establishing a detailed functional relation with the available crystallographic data. This study provided a comprehensive functional mapping of the FVIII C2 domain and discussed the implication of specific residues in respect to the maintenance in the activity and structure stability, the efficiency in secretion, the binding to phospholipids and the formation of epitope.

  4. Internal Maxillary Bypass for Complex Pediatric Aneurysms.

    Science.gov (United States)

    Wang, Long; Lu, Shuaibin; Qian, Hai; Shi, Xiang'en

    2017-07-01

    Complex pediatric aneurysms (PAs) are an unusual clinicopathologic entity. Data regarding the use of a bypass procedure to treat complex PAs are limited. Internal maxillary artery-to-middle cerebral artery bypass with radial artery graft was used to isolate PAs. Bypass patency and aneurysm stability were evaluated using intraoperative Doppler ultrasound, indocyanine green videoangiography, and postoperative angiography. Modified Rankin Scale was used to assess neurologic function. Over a 5-year period, 7 pediatric patients (≤18 years old) were included in our analysis. Mean age of patients was 14.4 years (range, 12-18 years), and mean size of PAs was 23.6 mm (range, 9-37 mm). All cases manifested with complex characteristics. Proximal artery occlusion was performed in 3 cases, complete excision following aneurysmal distal internal maxillary artery bypass was performed in 2 cases, and combined proximal artery occlusion and aneurysm excision was performed in the 2 remaining cases. Mean intraoperative blood flow was 61.6 mL/minute (range, 40.0-90.8 mL/minute). Graft patency rate was 100% during postoperative recovery and at the last follow-up examination (mean, 20 months; range, 7-45 months). All patients had excellent outcomes except for 1 patient who died of multiple-organ failure. Internal maxillary artery bypass is an essential technique for treatment of selected cases of complex PAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Are patients bypassing paediatric cardiology outreach clinics?

    Science.gov (United States)

    Fletcher, Alexander; Samson, Ray; McLeod, Karen

    2017-07-01

    Previous studies have identified that receiving specialist care close to home can positively influence patients' experience. Despite this, a review of cardiology outpatient appointments at the Royal Hospital for Children in Glasgow demonstrated that a large number of families are bypassing their local children's cardiology centre to attend cardiac clinics at the specialist children's surgical centre. We used patient questionnaire, audit of local facilities, and examined the relationship between diagnosis and bypass numbers to better understand factors influencing this trend. Our results suggest that patient preference, short travelling distance to specialist children's cardiac centre, a more severe cardiac diagnosis, and inconsistent local facilities, expertise, and support are likely to influence a family's decision to bypass their local children's cardiology centre.

  6. Doppler spectral characteristics of infrainguinal vein bypasses

    DEFF Research Database (Denmark)

    Nielsen, Tina G; von Jessen, F; Sillesen, H

    1993-01-01

    of arteriovenous fistulas the initially antegrade diastolic velocity was replaced by a retrograde flow within 3 months, whereas a forward flow in diastole was sustained in grafts with patent fistulas. Abnormal Duplex findings in 31 patients led to angiography and revision in 13 cases. Four revised grafts failed......, while nine remained patent at follow-up 1-12 months later. Ten (56%) of 18 non-revised bypasses with abnormal Duplex findings failed within 9 months compared to 1 (1%) of 76 bypasses with a normal velocity profile (p ... valuable information concerning haemodynamics of infrainguinal vein bypasses and identifies grafts at risk of thrombosis. Inclusion of low resistance index (detection of stenoses appears to improve the sensitivity of Duplex scanning....

  7. Minimally invasive coronary artery bypass grafting: a systematic review.

    Science.gov (United States)

    Kikuchi, Keita; Mori, Makoto

    2017-06-01

    To minimize surgical morbidity in coronary artery bypass grafting, minimally invasive cardiac surgery has gained popularity. Minimally invasive coronary artery bypass grafting offers unique advantages compared to conventional off-pump coronary artery bypass or minimally invasive direct coronary artery bypass in that it enables the surgeon to harvest and graft bilateral internal thoracic arteries via a small thoracotomy while being conducted completely off-pump. This review focuses on current evidence behind off-pump coronary artery bypass, multi-arterial revascularization, patient populations that would most benefit from bilateral internal thoracic artery minimally invasive coronary artery bypass grafting, the surgical technique, and early outcomes. By overcoming the perceived inability to utilize bilateral internal thoracic arteries in minimally invasive coronary artery bypass grafting, the new technique further expands the armamentarium of surgeons and cardiologists. Hybrid coronary revascularization with bilateral internal thoracic artery minimally invasive coronary artery bypass grafting further augments the appeal of the next generation of minimally invasive cardiac surgery.

  8. Gastric Bypass Surgery: What Happens If I Regain the Weight?

    Science.gov (United States)

    ... happens if you gain back weight after gastric bypass surgery? Answers from Katherine Zeratsky, R.D., L. ... If you begin to regain weight after gastric bypass surgery, talk to your doctor. You may have ...

  9. Analgesic Treatment in Laparoscopic Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenberg, Jacob

    2014-01-01

    This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines. The litera......This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines...

  10. Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue-treatment: effect of plasma source and treatment time.

    Science.gov (United States)

    Rapaille, André; Reichenberg, Stefan; Najdovski, Tome; Cellier, Nicolas; de Valensart, Nicolas; Deneys, Véronique

    2014-04-01

    The quality of fresh-frozen plasma is affected by different factors. Factor VIII is sensitive to blood component storage processes and storage as well as pathogen-reduction technologies. The level of fibrinogen in plasma is not affected by the collection processes but it is affected by preparation and pathogen-reduction technologies. The quality of plasma from whole blood and apheresis donations harvested at different times and treated with a pathogen-reduction technique, methylene blue/light, was investigated, considering, in particular, fibrinogen and factor VIII levels and recovery. The mean factor VIII level after methylene blue treatment exceeded 0.5 IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different series. The recovery of factor VIII was dependent on plasma source as opposed to treatment time. The interaction between the two factors was statistically significant. Mean levels of fibrinogen after methylene blue/light treatment exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment correlated strongly with the level before treatment. There was a negative correlation between fibrinogen level before treatment and recovery. Pearson's correlation coefficient between factor VIII recovery and fibrinogen recovery was 0.58. These results show a difference in recovery of factor VIII and fibrinogen correlated with plasma source. The recovery of both factor VIII and fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII and fibrinogen recovery did not appear to be correlated.

  11. 21 CFR 870.4240 - Cardiopulmonary bypass heat exchanger.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass heat exchanger. 870.4240... bypass heat exchanger. (a) Identification. A cardiopulmonary bypass heat exchanger is a device, consisting of a heat exchange system used in extracorporeal circulation to warm or cool the blood or...

  12. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass defoamer. 870.4230 Section... bypass defoamer. (a) Identification. A cardiopulmonary bypass defoamer is a device used in conjunction... entitled “Guidance for Extracorporeal Blood Circuit Defoamer 510(k) Submissions.” [45 FR 7907-7971, Feb. 5...

  13. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger. (b...

  14. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4400 Cardiopulmonary bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in...

  15. 21 CFR 870.4300 - Cardiopulmonary bypass gas control unit.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass gas control unit. 870.4300... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4300 Cardiopulmonary bypass gas control unit. (a) Identification. A cardiopulmonary bypass gas control unit is a device used...

  16. 21 CFR 870.4430 - Cardiopulmonary bypass intracardiac suction control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass intracardiac suction....4430 Cardiopulmonary bypass intracardiac suction control. (a) Identification. A cardiopulmonary bypass intracardiac suction control is a device which provides the vacuum and control for a cardiotomy return sucker...

  17. Outcomes after off-pump coronary bypass surgery

    NARCIS (Netherlands)

    Dijk, Diederik van

    2002-01-01

    The complications associated with in coronary artery bypass surgery (CABG) using cardiopulmonary bypass (CPB) have led to a renewed interest in coronary bypass surgery on the beating heart. The primary objective of the Octopus Study was to compare cognitive outcome between patients randomized to

  18. Recombinant factor VIII in the management of hemophilia A: current use and future promise

    Directory of Open Access Journals (Sweden)

    Jerry S Powell

    2009-05-01

    Full Text Available Jerry S PowellDivision of Hematology and Oncology, University of California Davis Cancer Center, Sacramento, CA, USAAbstract: Hemophilia A is a rare inherited bleeding disorder due to mutation of the gene that encodes the coagulation protein factor VIII. Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous bleeding or after injury, before reaching 20 years of age. One of the most impressive triumphs of modern medicine is that with current recombinant factor VIII replacement therapy, a boy born in the 21st century with severe hemophilia A can anticipate a normal life expectancy with essentially no permanent complications from bleeding. For severe hemophilia A, current optimal treatment should have two goals: first, to provide sufficient factor VIII to prevent spontaneous bleeding, and second, to provide sufficient factor VIII to have normal coagulation function after any trauma. However, the replacement therapy requires tremendous resources for effective use, and remains extraordinarily expensive. Thus there are opportunities for further advances in therapy for hemophilia A. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII, and second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. Because of the effectiveness of current therapy, any new developments in treatment will require significant concerns for safety, both immediate and in the long term. A number of research groups seek to prolong the biological efficacy of infused recombinant factor VIII. Currently, one such promising development is in the advanced stages of clinical trial. The goals will be to improve

  19. The F309S mutation increases factor VIII secretion in human cell line

    Directory of Open Access Journals (Sweden)

    Daianne Maciely Carvalho Fantacini

    2016-06-01

    Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

  20. Robotically-Assisted Coronary Artery Bypass Grafting

    Directory of Open Access Journals (Sweden)

    Thierry A. Folliguet

    2010-01-01

    Full Text Available Objectives. Robotic surgery enables to perform coronary surgery totally endoscopically. This report describes our experience using the da Vinci system for coronary artery bypass surgery. Methods. Patients requiring single-or-double vessel revascularization were eligible. The procedure was performed without cardiopulmonary bypass on a beating heart. Results. From April 2004 to May 2008, fifty-six patients were enrolled in the study. Twenty-four patients underwent robotic harvesting of the mammary conduit followed by minimal invasive direct coronary artery bypass (MIDCAB, and twenty-three patients had a totally endoscopic coronary artery bypass (TECAB grafting. Nine patients (16% were converted to open techniques. The mean total operating time for TECAB was 372±104 minutes and for MIDCAB was 220±69 minutes. Followup was complete for all patients up to one year. There was one hospital death following MIDCAB and two deaths at follow up. Forty-eight patients had an angiogram or CT scan revealing occlusion or anastomotic stenoses (>50% in 6 patients. Overall permeability was 92%. Conclusions. Robotic surgery can be performed with promising results.

  1. Bypassing BDD Construction for Reliability Analysis

    DEFF Research Database (Denmark)

    Williams, Poul Frederick; Nikolskaia, Macha; Rauzy, Antoine

    2000-01-01

    In this note, we propose a Boolean Expression Diagram (BED)-based algorithm to compute the minimal p-cuts of boolean reliability models such as fault trees. BEDs make it possible to bypass the Binary Decision Diagram (BDD) construction, which is the main cost of fault tree assessment....

  2. Planetary science: Bypassing the habitable zone

    Science.gov (United States)

    Ingersoll, Andrew P.

    2017-08-01

    In our own solar system, Venus is too hot, Mars is too cold and Earth is just right. Simulations show that making an icy planet habitable is not as simple as melting its ice: many icy bodies swing from too cold to too hot, bypassing just right.

  3. A Survey of Cache Bypassing Techniques

    Directory of Open Access Journals (Sweden)

    Sparsh Mittal

    2016-04-01

    Full Text Available With increasing core-count, the cache demand of modern processors has also increased. However, due to strict area/power budgets and presence of poor data-locality workloads, blindly scaling cache capacity is both infeasible and ineffective. Cache bypassing is a promising technique to increase effective cache capacity without incurring power/area costs of a larger sized cache. However, injudicious use of cache bypassing can lead to bandwidth congestion and increased miss-rate and hence, intelligent techniques are required to harness its full potential. This paper presents a survey of cache bypassing techniques for CPUs, GPUs and CPU-GPU heterogeneous systems, and for caches designed with SRAM, non-volatile memory (NVM and die-stacked DRAM. By classifying the techniques based on key parameters, it underscores their differences and similarities. We hope that this paper will provide insights into cache bypassing techniques and associated tradeoffs and will be useful for computer architects, system designers and other researchers.

  4. [ALK inhibitor].

    Science.gov (United States)

    Mano, Hiroyuki

    2011-01-01

    While lung cancer is the leading cause of cancer deaths worldwide, the molecular mechanism underlying its carcinogenesis is mainly unknown. We have discovered a small, fusion-type tyrosine kinase EML4-ALK that is generated through a tiny inversion within the short arm of human chromosome 2. Transgenic mice expressing EML4-ALK in lung developed hundreds of lung cancer nodules soon after birth, but such nodules were readily eradicated upon treatment with an ALK inhibitor. Clinical trials for EML4-ALK-positive lung cancer with an ALK inhibitor is ongoing, with its interim results being highly promising.

  5. Post-Bypass Extensive Ascites due to Splanchnic Bypass and the Effectiveness of Hyperalimentation Treatment

    Directory of Open Access Journals (Sweden)

    Veysel Temizkan

    2013-04-01

    Full Text Available Reperfusion edema may develop in the early periods of chronic ischemic tissue reperfusion. Reperfusion edema may be represented after the splanchnic bypass with ascites, abdominal distension, and liver and kidney function impairment. In this article, we are reporting the hyperalimentation treatment and its results for the common ascites and hepatorenal syndrome, after a coeliac and superior mesenteric artery bypass. [Arch Clin Exp Surg 2013; 2(2.000: 124-128

  6. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.

    Science.gov (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T

    2013-06-01

    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  7. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium.

    Science.gov (United States)

    van Hinsbergh, V W; Bertina, R M; van Wijngaarden, A; van Tilburg, N H; Emeis, J J; Haverkate, F

    1985-02-01

    Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator-inhibitor. High concentrations of thrombin-but not of factor Xa or IXa--had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.

  8. The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass.

    Science.gov (United States)

    Maslow, Andrew D; Stearns, Gary; Butala, Parag; Batula, Parag; Schwartz, Carl S; Gough, Jeffrey; Singh, Arun K

    2006-07-01

    Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.

  9. Angiogenesis Inhibitors

    Science.gov (United States)

    ... blood vessels “feed” growing tumors with oxygen and nutrients , allowing the cancer cells to invade nearby tissue , to move throughout ... any angiogenesis inhibitors currently being used to treat cancer in humans? Yes. The U.S. Food and Drug Administration (FDA) has approved bevacizumab to ...

  10. Baby hamster kidney cell-derived recombinant factor VIII: a quarter century of learning and clinical experience.

    Science.gov (United States)

    Afonja, Olubunmi; Kozak, Robert; Petraro, Paul; Michaels, Lisa A; Mathew, Prasad; Lemm, Georg; Kessler, Craig

    2016-12-01

    Management and care of individuals with hemophilia A advanced immensely with the introduction of recombinant factor VIII (rFVIII) replacement products. This review provides a historical overview of rFVIII development with a focus on Bayer's rFVIII (with albumin) and sucrose-formulated rFVIII (rFVIII-FS), the only rFVIII products cloned in baby hamster kidney (BHK) cells with >25 years of proven safety and efficacy. Areas covered: We review the advances in rFVIII technology and the efficacy and safety data for BHK-derived rFVIII/rFVIII-FS from clinical trials, investigator-initiated studies, and observational studies. Innovative products with new treatment potentials (eg, BAY 81-8973 and BAY 94-9027) built on this established safety and efficacy profile are also briefly discussed. The literature search strategy included targeted searches (PubMed) with manual article selection and other product-specific searches. Expert commentary: Development of rFVIII products and related improvements in viral safety and manufacturing efficiency have guaranteed an adequate supply of factor products worldwide and increased prophylaxis use. The net effects have been joint health preservation, reduction in morbidity and mortality, and quality-of-life enhancements. Current treatment challenges include lack of adherence to prophylaxis and inhibitor development; extended-half-life rFVIII products and non-FVIII replacement therapies in development may help overcome these challenges.

  11. Evolution of the European guidelines for the clinical development of factor VIII products: little progress towards improved patient management.

    Science.gov (United States)

    Mannucci, P M

    2013-05-01

    In the process of clinical development and licensing of factor VIII (FVIII) products for treatment of haemophilia A, the safety concerns generated in the 1980s by the risk of pathogen transmission were tremendously reduced by the implementation of an array of methods for inactivation/removal of blood borne pathogens. The current focus on the risk of FVIII inhibitors does not stem from a new awareness, because this multifactorial complication has long been recognized. With this background, I believe that the current European regulatory guidelines for the clinical development and licensing of FVIII products fail to reflect the tremendous progress made in terms of clinical efficacy and safety, because they are witnessing a continuous increase in the demands from health agencies to the point that clinical studies have become more and more difficult to carry out. This article reviews the evolution of the European regulations on new FVIII products, lists a number of regulatory requirements whose scientific and/or clinical rationale is perhaps questionable and recommends keeping such requirements in reasonable limits of feasibility, without jeopardizing current high standards of efficacy and safety. © 2012 Blackwell Publishing Ltd.

  12. Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A.

    Science.gov (United States)

    Kruse-Jarres, R; St-Louis, J; Greist, A; Shapiro, A; Smith, H; Chowdary, P; Drebes, A; Gomperts, E; Bourgeois, C; Mo, M; Novack, A; Farin, H; Ewenstein, B

    2015-03-01

    Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI-1 is an investigational, B-domain deleted, recombinant FVIII, porcine sequence, with low cross-reactivity to anti-hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI-1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg(-1) , OBI-1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI-1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti-porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI-1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI-1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients. © 2015 John Wiley & Sons Ltd.

  13. Concomitant aorto-right subclavian artery bypass with off-pump coronary artery bypass grafting: a case report.

    Science.gov (United States)

    Tazume, Hirokazu; Okamoto, Ken; Fukui, Toshihiro

    2017-10-11

    Atherosclerotic stenosis of the brachiocephalic artery sometimes occurs in patients with coronary artery disease, and can cause stroke during the perioperative period of coronary artery bypass grafting. We describe the case of a 77-year old male with severe stenosis of the brachiocephalic artery and severe coronary artery disease. He successfully underwent aorto-right subclavian artery bypass that was performed concomitantly with off-pump coronary artery bypass. Concomitant aorto-subclavian artery bypass with off-pump coronary artery bypass grafting is a therapeutic option that minimizes the risk of perioperative stroke in patients with brachiocephalic artery stenosis and coronary artery disease.

  14. Drevnerusskij pamflet na Mihaila VIII Paleologa v svete germenevtičeskogo analiza

    Directory of Open Access Journals (Sweden)

    Demincev Mihail

    2015-01-01

    Full Text Available In the article the perception of the image of Michael VIII Palaeologus by literate citizens of Tsardom of Russia is considered. The study is based on analysis of writings that date back to XVII century. The study focuses on identifying the symbols and latent ideas, that point to a semantic connection of the studied writings with The Old Testament, Apocalypse and some antique texts. In the end of the article the authjr makes a conclusion, that the perception of the image of Michael VIII Palaeologus in Tsardom of Russia was negative.

  15. Wavelengths and energy levels of Xe VII and Xe VIII obtained by collision-based spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, M.O. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Gonzalez, A.M. [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain). Inst. de Investigacion Basica; Hallin, R. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Heijkenskjoeld, F. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Hutton, R. [Lund Univ. (Sweden). Dept. of Physics; Langereis, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Nystroem, B. [Lund Univ. (Sweden). Dept. of Physics; O`Sullivan, G. [University Coll., Dublin (Ireland). Dept. of Physics; Waennstroem, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics

    1995-01-01

    The Xe VII and Xe VIII spectra have been investigated by collision-based spectroscopy. The radiation emitted following electron capture by 10q keV Xe{sup q+} ions (q = 6-8) impinging on a He (Ar) gas target has, with some exceptions, been recorded in the 350-8000 (1200-2500) A wavelength region. The xenon ions were provided by the Uppsala University ECR ion source. Many of the observed, previously unreported spectral lines have been identified. In total, nine new energy levels of Xe VII and Xe VIII have been established, of which two are tentative. The analysis was supported by Hartree-Fock calculations. (orig.).

  16. SUrgical versus PERcutaneous Bypass : SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Lensvelt, Mare M. A.; Holewijn, Suzanne; Fritschy, Wilbert M.; Wikkeling, Otmar R. M.; van Walraven, Laurens A.; de Vries, Bas M. Wallis; Zeebregts, Clark J.; Reijnen, Michel M. P. J.

    2011-01-01

    Background: Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic

  17. SUrgical versus PERcutaneous Bypass: SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Lensvelt, M.M.A.; Holewijn, S.; Fritschy, W.M.; Wikkeling, O.R.; Walraven, L.A. van; Wallis de Vries, B.M.; Zeebregts, C.J.A.; Reijnen, M.M.P.J.

    2011-01-01

    BACKGROUND: Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic

  18. 46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of division 1 of section VIII of the ASME... division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. (a) Pressure vessels shall be designed, constructed, and inspected in accordance with section VIII of the ASME Boiler and Pressure Vessel...

  19. Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations

    NARCIS (Netherlands)

    Loomans, J.I.; Velzen, A.S. van; Eckhardt, C.L.; Peters, M.; Makipernaa, A.; Holmstrom, M.; Brons, P.P.T.; Dors, N.; Haya, S.; Voorberg, J.; Bom, J.G. Van Der; Fijnvandraat, K.

    2017-01-01

    Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels.

  20. [Robot-assisted Coronary Artery Bypass Grafting].

    Science.gov (United States)

    Ishikawa, Norihiko; Watanabe, Go

    2016-07-01

    The application for robot-assisted coronary surgery ranges from internal thoracic artery (ITA) harvesting with hand-sewn anastomoses to totally endoscopic coronary artery bypass grafting (TECAB), either on- or off-pump. The bilateral IMA can be harvested with the aid of a surgical robot and then multivessel bypass grafting can follow. Such robot-assisted minimally invasive direct coronary artery bypass grafting is called "ThoraCAB". Surgical robots cannot only endoscopically harvest the ITA but they can also anastomose the coronary artery in TECAB. But TECAB still has the difficulties, such as narrow surgical field in Japanese patients. Both procedures have the significant advantages of minimizing surgical trauma, such as reduced comlications, faster return back to normal activities and being improved cosmesis, and which have resulted in the development of minimally invasive surgery. Robot-assisted cardiac surgery for structural heart disease has been approved by the Ministry of Health, Labour and Welfare (MHLW) since December 2015, however, robot-assisted cardiac surgery for TECAB has not been approved yet in Japan.

  1. Steam by-pass reciprocating rod pump

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, B. [Weatherford, Edmonton, AB (Canada)

    2008-07-01

    This article presented the design details of Weatherford's steam by-pass reciprocating rod rod pump which was designed to work under specific well conditions and individual applications, including Imperial Oil's Cold Lake bitumen recovery project located 230 km northeast of Edmonton, Alberta. Imperial Oil uses a cyclic steam stimulation (CSS) process to enhance bitumen recovery from the Clearwater oil sand reservoir. A typical wellbore reach can be up to 700 m and 80 degrees deviation at a target depth of 455 m TVD. These long well bore reaches along with high bottomhole angles and high produced fluid viscosities complicate the design of the artificial lift, which is essentially a modified conventional API pump. The hold-down section is a friction ring design incorporating stainless steel friction rings to provide positive holding force. The steam by-pass coupling is a reduced-diameter tube fitting between the API pump and the friction ring hold-down section. Three stages of the Imperial Cold Lake operation were described, namely the steam injection stage, soak phase stage and production stage. Typically, the steam by-pass pump is suspended in the tubing for the entire cycle. This presentation reviewed the operating steps of the pump, whose average run time in the field is about 15 months, depending on the potential for scaling or sand influx. tab., figs.

  2. Patient's Perception About Coronary Artery Bypass Grafting

    Directory of Open Access Journals (Sweden)

    Kelminda Maria Bulhões Mendonça

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVE: The diagnosis of coronary artery disease referred for heart surgery has an important psychological component. The purpose of this study was to access the difficulties experienced by individuals awaiting coronary artery bypass grafting and to determine strategies that facilitate adaptation to a new lifestyle, modified by the disease. METHODS: A qualitative, exploratory study involving patients admitted to a university teaching hospital in the city of Salvador, Bahia, Brazil, awaiting coronary artery bypass grafting. Semi-structured interviews were performed in accordance with a previously defined script based on the study objective. Each transcription was read in its entirety to verify the representativeness, homogeneity and pertinence of the data obtained (pre-analysis, followed by separation of categories of analysis. RESULTS: The descriptions of this study show that patients admitted to the completion of coronary artery bypass grafting experience a wide range of psychological difficulties, considering that surgery acquires interpretations that vary according to individuals' subjectivity. The patients recognized the benefit of being able to discuss their feelings as a means of diminishing their fear and anxiety. CONCLUSION: Helping patients find resources to confront more positively the daily hospitalization is an important aspect for the health care professionals who assist them. This goal can be achieved through modification of the biomedical model of care for a biopsychosocial view. The investment of time and attention is of fundamental importance and aims to overcome existing deficiencies that interfere with the outcome of patients after cardiac surgery.

  3. Desain Pembelajaran Materi Luas Permukaan Prisma Menggunakan Pendekatan PMRI bagi Siswa Kelas VIII

    Directory of Open Access Journals (Sweden)

    Djuwita Trisnawati

    2015-08-01

    Full Text Available Penelitian ini bertujuan menghasilkan lintasan belajar untuk membantu siswa dalam pembelajaran luas permukaan prisma menggunakan kemasan produk di kelas VIII SMP. Penelitian ini berdasarkan PMRI yang dikaitkan dengan pembelajaran Kurikulum 2006/KTSP. Metode yang digunakan dalam penelitian ini adalah design research type validation study yang bertujuan untuk membuktikan teori-teori pembelajaran. Penelitian ini dilaksanakan di SMP Negeri 24 Palembang dengan melibatkan siswa kelas VIII yang berjumlah 31 siswa. Aktivitas-aktivitas pembelajaran yang dilakukan siswa meliputi: 1 memahami bentuk dan sifat prisma, 2 menemukan dan memahami konsep luas permukaan prisma, dan 3 menyelesaikan permasalahan dalam kehidupan sehari-hari yang berhubungan dengan luas permukaan prisma. Hasil dari penelitian ini menunjukkan bahwa melalui serangkaian aktivitas yang telah dilakukan membantu siswa dalam pembelajaran luas permukaan prisma.This research aimed to produce learning trajectory in learning surface area of prism using product packaging in class VIII. This study was based PMRI associated with learning curriculum 2006 / KTSP. The method used was design research of type validation study that aimed to prove the theories of learning. The research was conducted on 31 students of class VIII SMPN 24 Palembang. Students learning activities that were conducted including: (1 comprehending the shape and the characteristic of prism, (2 finding and comprehending the concept surface area of prism, and (3 solving the problems in daily life related to the surface area of prism. The results of this study indicate that a series of activities can help students in learning surface area of prism.

  4. A natural anatoxin, Amm VIII, induces neutralizing antibodies against the potent scorpion alpha-toxins.

    Science.gov (United States)

    Martin-Eauclaire, M-F; Alami, M; Giamarchi, A; Missimilli, V; Rosso, J-P; Bougis, P E

    2006-03-15

    In this study, we have used Amm VIII, a natural anatoxin from the scorpion Androctonus mauretanicus mauretanicus, to elicit specific polyclonal antibodies in rabbit. Using liquid-phase radioimmunoassay, we have studied its selectivity and its neutralizing activity both in vitro and in vivo for the most lethal scorpion alpha-toxins described, in particular the alpha-toxin of reference AaH II. We have shown that the anti-Amm VIII serum prevents the association of 125I-AaH II with its receptor and is able to remove 125I-AaH II already bound to its site (the half-life of the complex 125I-AaH II-receptor site was 12 min in the absence of anti-Amm VIII serum but decreased to only 2 min in the presence of anti-Amm VIII serum). In vivo, the serum also has a protective effect in mice: 42 LD50 of AaH II by millilitre are neutralized, measured by subcutaneous injection.

  5. Analysis of mutations in the entire coding sequence of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Bidichadani, S.I.; Lanyon, W.G.; Connor, J.M. [Glascow Univ. (United Kingdom)] [and others

    1994-09-01

    Hemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of RT-PCR of ectopic factor VIII transcripts and genomic DNA-PCRs to amplify the entire essential sequence of the factor VIII gene. This is followed by chemical mismatch cleavage analysis and direct sequencing in order to facilitate a comprehensive search for mutations. We describe the characterization of nine potentially pathogenic mutations, six of which are novel. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations detected, we have analyzed them for evolutionary sequence conservation and for their involvement of sequence motifs catalogued in the PROSITE database of protein sites and patterns.

  6. In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A

    NARCIS (Netherlands)

    Vossebeld, P. J. M.; Tissing, M. H.; van den Berg, H. M.; Leebeek, F. W. G.; de Goede-Bolder, A.; Novakova, I. R. O.; Gerrits, W. B. J.; Peters, M.; Koopman, M. M. W.; Faber, A.; Hiemstra, H.; Grob, P.; Strengers, P. F. W.

    2003-01-01

    AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance

  7. Intercombination lines of AlVIII, AlIX, and AlX ions

    Science.gov (United States)

    Denne, B.; Hinnov, E.

    1984-06-01

    Several aluminum lines observed in the Princeton Large Torus tokamak discharges have been identified as intersystem transitions, establishing the energies of the Al VIII 2s2p35S, Al IX 2s2p24P, and Al X 2s2p3P terms. Some observations of isoelectronic transitions in scandium and titanium ions are also reported.

  8. Living in a physical world VIII. Gravity and life in water

    Indian Academy of Sciences (India)

    2006-07-31

    Jul 31, 2006 ... Home; Journals; Journal of Biosciences; Volume 31; Issue 3. Living in a physical world VIII. Gravity and life in water. Steven Vogel. Series Volume 31 Issue 3 September 2006 pp 309-322. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jbsc/031/03/0309-0322 ...

  9. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

    2017-01-01

    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  10. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  11. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  12. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII

    NARCIS (Netherlands)

    van Haren, Simon D.; Wroblewska, Aleksandra; Herczenik, Eszter; Kaijen, Paul H.; Ruminska, Aleksandra; ten Brinke, Anja; Meijer, Alexander B.; Voorberg, Jan

    2013-01-01

    The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the

  13. Molecular characterization of a novel family VIII esterase from burkholderia multivorans UWC10

    CSIR Research Space (South Africa)

    Rashamuse, KJ

    2007-02-01

    Full Text Available was identified. Full-length sequencing of the DNA insert showed that it consisted of a single open reading frame (ORF1) encoding a predicted protein of 398 amino acids. ORF1 (termed EstBL) had a high protein sequence identity to family VIII esterases. The Est...

  14. Beating heart axillocoronary bypass for management of the untouchable ascending aorta in coronary artery bypass grafting.

    Science.gov (United States)

    Bonatti, J; Hangler, H; Oturanlar, D; Posch, L; Müller, L C; Voelckel, W; Schwarz, B; Bodner, G

    1999-11-01

    Cannulation and clamping of a severely atherosclerotic ascending aorta during coronary artery bypass grafting (CABG) can lead to cerebral embolization of atheromatous debris and should therefore be avoided whenever possible. A variety of surgical techniques including performance of extraanatomical coronary bypass conduits has been described to solve this problem. We report on a preliminary series of four patients in whom the axillary artery was used as an inflow vessel for venous coronary artery bypass grafts which were performed on the beating heart in order to achieve an aortic no touch concept. The axillary artery was exposed between the pectoralis major muscle and the deltoid muscle via an infraclavicular incision. A saphenous vein graft of at least 40 cm in length was sutured to the axillary artery and then brought into the pericardial cavity following an intercostal and transpleural route. The graft was anastomosed to the target vessel using local coronary occlusion. The procedure was carried out via sternotomy in three patients who also received additional internal mammary artery in situ grafts for adequate coronary revascularization. In one high risk patient an isolated axillocoronary bypass was performed in a minimally invasive fashion via anterolateral minithoracotomy. The procedure was completed without major technical difficulties in all four patients. The mean graft length required was 33.2 +/- 1.6 cm, postoperative ultrasonic duplex scans of the axillocoronary grafts revealed a mean flow of 62.5 +/- 23.6 ml/min. No stroke or brachial plexus injury occurred. Three patients are in angina class I (Canadian Cardiovascular Society Classification), one patient is in class II postoperatively. After a mean follow-up of 11.5 +/- 6.6 months postoperatively all grafts remain patent. Axillocoronary bypass grafting can be easily performed for management of the untouchable ascending aorta. Straightforward surgical technique and the accessibility to noninvasive

  15. VIII Olimpíada Brasileira de Astronomia e Astronáutica

    Science.gov (United States)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria

    2007-07-01

    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.

  16. RELATIONSHIP OF INTEREST, LEARNING MOTIVATION AND ATTITUDE WITH RESULTS LEARNING CLASS VIII SMP STATE 13 MAKASSAR

    Directory of Open Access Journals (Sweden)

    Putri Athirah Azis

    2016-12-01

    Full Text Available The study aims at examining (1 the correlation of learning interest towards learning result of grade students, (2 the correlation of learning motivation towards learning result of grade students, (3 the correlation of students attitude towards learning result, (4 the correlationof interest, learning motivation, and attitude collaboratively towards learning result. The study is an ex post facto. The population of the study was grade VIII at SMPN 13 Makassar. Samples were 105 students taken by employing random sampling technique. Data were collected through questionnaire and documentation. Data were analyzed using regression test. The result of study reveal that (1 there is significant correlation (p<0,01 of interest towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,718 and its effectiveness contribution (R2 is 51,5%, (2 there is significant correlation (p<0,01 of motivation towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,775 and its effectiveness contribution (R2 is 60,1%, (3 there is significant correlation (p<0,01 of attitude towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,737 and its effectiveness contribution (R2 is 54,4%, (4 there is significant correlation (p<0,01 of interest, motivation and attitude collaboratively towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,861 and its effectiveness contribution (R2 is 74,1%,

  17. A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

    Science.gov (United States)

    Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

    2016-02-01

    Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to

  18. Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses

    DEFF Research Database (Denmark)

    Nielsen, Tina G; Djurhuus, Christian Born; Morre-Pedersen, Erik

    1996-01-01

    PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced...... hemodynamic conditions of a more severe stenosis. Assessment of the hemodynamic impact of fistulas must be undertaken in the evaluation of in situ vein bypass stenoses....

  19. Extra-intracranial standard bypass in the elderly

    DEFF Research Database (Denmark)

    Sandow, Nora; von Weitzel-Mudersbach, Paul; Rosenbaum, Sverre

    2013-01-01

    Patients with chronic atherosclerotic vessel occlusion and cerebrovascular hemodynamic insufficiency may benefit from extra-intracranial (EC-IC) bypass surgery. Due to demographic changes, an increasing number of elderly patients presents with cerebrovascular hemodynamic insufficiency. So far......, little data for EC-IC bypass surgery in elderly patients suffering occlusive cerebrovascular disease are available. We therefore designed a retrospective study to address the question whether EC-IC bypass is a safe and efficient treatment in a patient cohort ≥70 years....

  20. Cardioprotective Effect of Ghrelin in Cardiopulmonary Bypass Involves a Reduction in Inflammatory Response

    Science.gov (United States)

    Ma, Heng; Yi, Dinghua; Gu, Chunhu; Yu, Shiqiang

    2013-01-01

    Background Ghrelin has been reported to protect the cardiovascular system; however, the cardioprotective effect of ghrelin against cardiopulmonary bypass (CPB) induced myocardial injury are unclear. In this study, the protective effect of ghrelin on CPB induced myocardial injury and the underlying mechanisms were investigated. Methods and Results Adult male rats were subjected to CPB and randomly to receive vehicle (n = 8), ghrelin (n = 8), ghrelin plus [D-Lys3]-GHRP-6, a GHSR-1a inhibitor (n = 8), or ghrelin plus wortmannin, a phosphoinositide 3′-kinase (PI3K) inhibitor (n = 8). In vitro study was performed on cultured cardiomyocytes subjected to simulated cardiopulmonary bypass (SCPB). Ghrelin attenuated the inflammatory response, as evidenced by reduced induction of TNF-α, IL-6 and myocardial myeloperoxidase activity and concurrent reduction in apoptosis, oxidative stress, and levels of myocardial injury markers following CPB. Moreover, ghrelin significantly increased cardiac function after CPB. In cultured cardiomyocytes subjected to simulated CPB, ghrelin increased cell viability and decreased the percentage of apoptotic myocytes. Inhibition of ghrelin downstream signaling blocked the cardioprotective effects both in vivo and vitro. Conclusions Ghrelin could provide an effective approach to the attenuation of CPB induced myocardial injury. The cardioprotective effects elicited by ghrelin may contribute to the inhibition of inflammatory response through the Akt-activated pathway. PMID:23359315

  1. Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.

    Science.gov (United States)

    Cao, Yukun; Tang, Jun; Yang, Ting; Ma, Heng; Yi, Dinghua; Gu, Chunhu; Yu, Shiqiang

    2013-01-01

    Ghrelin has been reported to protect the cardiovascular system; however, the cardioprotective effect of ghrelin against cardiopulmonary bypass (CPB) induced myocardial injury are unclear. In this study, the protective effect of ghrelin on CPB induced myocardial injury and the underlying mechanisms were investigated. Adult male rats were subjected to CPB and randomly to receive vehicle (n = 8), ghrelin (n = 8), ghrelin plus [D-Lys3]-GHRP-6, a GHSR-1a inhibitor (n = 8), or ghrelin plus wortmannin, a phosphoinositide 3'-kinase (PI3K) inhibitor (n = 8). In vitro study was performed on cultured cardiomyocytes subjected to simulated cardiopulmonary bypass (SCPB). Ghrelin attenuated the inflammatory response, as evidenced by reduced induction of TNF-α, IL-6 and myocardial myeloperoxidase activity and concurrent reduction in apoptosis, oxidative stress, and levels of myocardial injury markers following CPB. Moreover, ghrelin significantly increased cardiac function after CPB. In cultured cardiomyocytes subjected to simulated CPB, ghrelin increased cell viability and decreased the percentage of apoptotic myocytes. Inhibition of ghrelin downstream signaling blocked the cardioprotective effects both in vivo and vitro. Ghrelin could provide an effective approach to the attenuation of CPB induced myocardial injury. The cardioprotective effects elicited by ghrelin may contribute to the inhibition of inflammatory response through the Akt-activated pathway.

  2. Obstetrical and neonatal outcomes in women following gastric bypass

    DEFF Research Database (Denmark)

    Berlac, Janne Foss; Skovlund, Charlotte Wessel; Lidegaard, Ojvind

    2014-01-01

    OBJECTIVE: To assess obstetrical and neonatal outcomes in women following gastric bypass, compared with adipose women without surgery and with a normal weight control population. DESIGN: Historical controlled cohort study. SETTING: Denmark. POPULATION: All women undergoing gastric bypass during...... the period 1996-2011, and subsequently giving birth. METHODS AND MAIN OUTCOME MEASURES: Obstetrical and neonatal outcomes in women without gastric bypass matched on age, parity, plurality, year, and body mass index, and normal weight women. RESULTS: In 415 women giving birth after gastric bypass we found...

  3. Arterial Filter Bypass Loop: What Occurs in this Area during Cardiopulmonary Bypass and Are There Potential Patient Implications

    Science.gov (United States)

    Hawkins, Justin L.; Myers, Gerard J.; Légaré, Jean-Francois; Swyer, Wilfred

    2010-01-01

    Abstract: The arterial filter is an integral part of bypass circuitry. When introduced, manufacturers suggested a bypass loop for retrograde priming and de-airing, and for uninterrupted blood flow in case of malfunction. Practice has shown antegrade priming and de-airing is possible. This questions the necessity of the loop and presents the question—what occurs in the loop during bypass? After obtaining Human Research Ethics Board approval, eight consecutive patients (n = 8) were chosen for this study. Exclusive exclusion criterion was receiving any transfusions during cardiopulmonary bypass, as this could possibly influence results. The choice of patient numbers was based simply on proof of concept. Investigation involved isolation and collection of loop contents after cardiopulmonary bypass was completed. Testing included complete blood count, prothrombin time, international normalized ratio, partial thromboplastin time, activated clotting time, plasma free hemoglobin, slide photography with analysis for platelet clumping, and debris detection. One perfusionist collected samples, providing uniform collection and isolation technique. Regular blood samples were collected from the bypass circuitry, and from patients’ pre-operative blood work. Analysis of data revealed that platelet counts in the bypass loops were statistically lower than control. Evidence of platelet clumping was present in 3 of 8 bypass loop samples, representing 37.5% of the study population. There was no clumping detected in any of the controls. In patients where platelet clumping was present, a positive correlation was noted between mean bypass time and size of platelet clumps. Prothrombin time and international normalized ratio results were immeasurable. Hemoglobin levels were higher in the loop samples. There was no evidence of debris or fibrin monomer present in any of the samples analyzed. The study results indicate that during “normal” cardiopulmonary bypass with an arterial filter

  4. Indications and Outcomes of Prophylactic and Therapeutic Extracranial-to-intracranial Arterial Bypass for Cerebral Revascularization

    Directory of Open Access Journals (Sweden)

    Emre Gazyakan, MD, MSc

    2015-04-01

    Conclusions: The collaboration of neurosurgeons and plastic surgeons in performing EC-IC bypass can result in excellent outcomes with a high bypass patency rate and few complications, particularly for prophylactic EC-IC bypass.

  5. Reoperative coronary bypass grafting without cardiopulmonary bypass through a small thoracotomy

    NARCIS (Netherlands)

    Boonstra, PW; Grandjean, JG; Mariani, MA

    Background. The danger of coronary reoperations is mainly hidden in the reopening of the sternum and in the manipulation of the heart and the old grafts. Therefore, the minimally invasive direct coronary artery bypass procedure seems an ideal technique for coronary reoperations if only the left

  6. Bypassing the bandwidth theorem with PT symmetry

    CERN Document Server

    Ramezani, Hamidreza; Ellis, F M; Guenther, Uwe; Kottos, Tsampikos

    2012-01-01

    The beat time {\\tau}_{fpt} associated with the energy transfer between two coupled oscillators is dictated by the bandwidth theorem which sets a lower bound {\\tau}_{fpt}\\sim 1/{\\delta}{\\omega}. We show, both experimentally and theoretically, that two coupled active LRC electrical oscillators with parity-time (PT) symmetry, bypass the lower bound imposed by the bandwidth theorem, reducing the beat time to zero while retaining a real valued spectrum and fixed eigenfrequency difference {\\delta}{\\omega}. Our results foster new design strategies which lead to (stable) pseudo-unitary wave evolution, and may allow for ultrafast computation, telecommunication, and signal processing.

  7. TRAS principles blight arterial bypass and plasty.

    Directory of Open Access Journals (Sweden)

    Kothari M

    1997-04-01

    Full Text Available A new concept--Tissue Requisitions (Principle I/Relinquishes (Principle II Arterial Supply--of TRAS principles is introduced to help appreciate the failures/successes of modern medicine′s attempts at restoring arterial flow in luminally compromised coronary/carotid fields, an invasive branch rightly called vascular ReRheology, which comprises diagnosing/treating arterial blocks. The technical wizardry of arterial reconstruction (bypass or lumen--restoration (plasty has to reckon with the TRAS principles all the time.

  8. Flow characteristics in narrowed coronary bypass graft

    Energy Technology Data Exchange (ETDEWEB)

    Bernad, S. I. [Romanian Academy – Timisoara Branch, Mihai Viteazul Str. 24, RO-300223, Timisoara (Romania); Bosioc, A.; Totorean, A. F. [University Politehnica of Timisoara, Department of Hydraulic Machinery, Mihai Viteazul Str. 1, RO-300222, Timisoara (Romania); Bernad, E. S.; Petre, I. [University of Medicine and Pharmacy Victor Babes Timisoara, P-ta Eftimie Murgu, 2, Timisoara (Romania)

    2016-06-08

    Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

  9. Work on the Geneva motorway bypass

    CERN Multimedia

    État de Genève, DCTI, Direction du génie civil

    2006-01-01

    Work on the airport section of the Geneva motorway bypass is continuing and will require the temporary closure of two sliproads allowing traffic to make a U-turn near the airport and the Palexpo exhibition centre. The sliproads on the French and Lausanne sides will be closed until autumn 2006. U-turns will still be possible via clearly marked deviations. For further information: www.autoroute-aeroport.ch We would like to thank you in advance for your understanding. Civil Engineering Department, DCTI, State of Geneva

  10. Emergency laparoscopic conversion from mini/one anastomosis gastric bypass to modified Roux-en-Y-gastric bypass due to acute bleeding from a recurrent marginal ulcer.

    Science.gov (United States)

    Godina, Mario; Nagliati, Carlo; Menegon, Paola; Caruso, Valentina

    2017-09-01

    Our aim is to present the laparoscopic technique of an emergency revisional procedure performed to convert a mini/one anastomosis gastric bypass (MGB/OAGB) to a modified Roux-en-Y-gastric-bypass (RYGB) due to recurrent bleeding from a marginal ulcer. A 43 year old woman presented unstable conditions due to acute bleeding from a marginal ulcer after a MGB/OAGB performed 3 years before. After three failed endoscopic haemostasis attempts, she underwent a laparoscopic conversion to a modified RYGB in emergency setting. The patient had an uneventful recovery. She maintained heamodynamical stability after the procedure. She was eventually discharged in the seventh postoperative day after restarting oral feeding on chronic proton pump inhibitors. To our knowledge, there are few descriptions of emergency surgical conversion from a MGB/OAGB to a modified laparoscopic RYGB due to a recurrent marginal ulcer bleeding not responsive to endoscopic treatment. A regular post-operative follow-up is mandatory after bariatric surgery. We advocate performing revisional surgery in an experienced Bariatric Center.

  11. Allergic reaction in a cohort of haemophilia A patients using plasma-derived factor VIII (FVIII) concentrate is rare and not necessarily triggered by FVIII.

    Science.gov (United States)

    Montalvão, S A L; Tucunduva, A C; Siqueira, L H; Sambo, A L A; Medina, S S; Ozelo, M C

    2015-07-01

    In contrast to haemophilia B, allergic manifestations are rare complications in haemophilia A (HA) patients treated with factor VIII (FVIII) concentrates. Nevertheless, it can be serious and hamper replacement therapy in these cases. The aims of this study were to evaluate the frequency of allergic reaction in a cohort of HA patients treated only with plasma-derived FVIII (pdFVIII) concentrates, and assess the possible immune mechanisms involved. History of allergic reaction was retrospectively assessed. Patients with allergic manifestations were followed, and had plasma samples collected in different timepoints in relation to the allergic episode. These samples were analysed for the presence of inhibitor and anti-FVIII immunoglobulins subclasses. Three of 322 HA patients (0.9%) developed allergic reaction after exposure to pdFVIII products during the last 15 years in our centre. The first patient, with severe HA, without inhibitor, had anti-pdFVIII IgE and IgG4, but no anti-recombinant FVIII (rFVIII) IgE. The second patient, with severe HA, and high-responding inhibitor, presented allergic manifestation with both, pdFVIII concentrate and activated prothrombin complex concentrate. Although anti-pdFVIII and anti-rFVIII IgG4 were detected, no anti-FVIII IgE was present. The third patient, with moderate HA without inhibitor, atopic, had no anti-FVIII immunoglobulin detected, and allergic symptoms disappeared after switching to rFVIII concentrate. This study corroborates the low incidence of allergic reactions in HA patients. In the three cases presented, the anti-FVIII immunoglobulin profile demonstrated that the allergic manifestation was triggered by other proteins contained in pdFVIII products, and not directed to FVIII. © 2015 John Wiley & Sons Ltd.

  12. Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity.

    Science.gov (United States)

    Kuether, E L; Schroeder, J A; Fahs, S A; Cooley, B C; Chen, Y; Montgomery, R R; Wilcox, D A; Shi, Q

    2012-08-01

    The development of inhibitory antibodies, referred to as inhibitors, against exogenous factor VIII in a significant subset of patients with hemophilia A remains a persistent challenge to the efficacy of protein replacement therapy. Our previous studies using the transgenic approach provided proof-of-principle that platelet-specific expression could be successful in treating hemophilia A in the presence of inhibitory antibodies. To investigate a clinically translatable approach for platelet gene therapy of hemophilia A with pre-existing inhibitors. Platelet FVIII expression in preimmunized FVIII(null) mice was introduced by transplantation of lentivirus-transduced bone marrow or enriched hematopoietic stem cells. FVIII expression was determined with a chromogenic assay. The transgene copy number per cell was quantitated with real-time PCR. Inhibitor titer was measured with the Bethesda assay. Phenotypic correction was assessed by the tail clipping assay and an electrolytically induced venous injury model. Integration sites were analyzed with linear amplification-mediated PCR. Therapeutic levels of platelet FVIII expression were sustained in the long term without evoking an anti-FVIII memory response in the transduced preimmunized recipients. The tail clip survival test and the electrolytic injury model confirmed that hemostasis was improved in the treated animals. Sequential bone marrow transplants showed sustained platelet FVIII expression resulting in phenotypic correction in preimmunized secondary and tertiary recipients. Lentivirus-mediated platelet-specific gene transfer improves hemostasis in mice with hemophilia A with pre-existing inhibitors, indicating that this approach may be a promising strategy for gene therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory antibodies. © 2012 International Society on Thrombosis and Haemostasis.

  13. Inhibitor development and mortality in non-severe hemophilia A.

    Science.gov (United States)

    Eckhardt, C L; Loomans, J I; van Velzen, A S; Peters, M; Mauser-Bunschoten, E P; Schwaab, R; Mazzucconi, M G; Tagliaferri, A; Siegmund, B; Reitter-Pfoertner, S E; van der Bom, J G; Fijnvandraat, K

    2015-07-01

    The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. During 64,200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64 years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71 years (IQR, 60-81). In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was > 5 times increased compared with that for those without inhibitors (age-adjusted mortality rate ratio, 5.6). Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients. © 2015 International Society on Thrombosis and Haemostasis.

  14. 75 FR 26196 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII...

    Science.gov (United States)

    2010-05-11

    ..., (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, Forest Service, USDA. ACTION... 39269. SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108...

  15. DAMPAK POSITIF DAN NEGATIF SOSIAL MEDIA TERHADAP PENDIDIKAN AKHLAK ANAK (Studi Kasus di SMP Negeri 2 Kelas VIII Banda Aceh)

    National Research Council Canada - National Science Library

    NISA KHAIRUNI

    2016-01-01

    The author examines the positive and negative effects of social media on the moral education of children in school SMPN 2 class VIII Banda Aceh, it is very interesting because of the many children who abuse social media...

  16. A novel approach in potential anticoagulants from peptides epitope 558-565 of A2 subunit of factor VIII.

    Science.gov (United States)

    Anastasopoulos, C; Sarigiannis, Y; Stavropoulos, G

    2013-04-01

    Factor VIII, a human blood plasma protein, plays an important role during the intrinsic pathway of blood coagulation cascade after its activation by thrombin. The activated form of FVIII acts as cofactor to the serine protease Factor IXa, in the conversion of the zymogen Factor X to the active enzyme Factor Xa. The Ser558-Gln565 region of the A2 subunit of Factor VIII has been shown to be crucial for FVIIIa-FIXa interaction. Based on this, a series of linear peptides, analogs of the 558-565 loop of the A2 subunit of the heavy chain of Factor VIII were synthesized using the acid labile 2-chlorotrityl chloride resin and biologically evaluated in vitro by measuring the chronic delay of activated partial thromboplastin time and the inhibition of Factor VIII activity, as potential anticoagulants.

  17. Diagnostic tools for post-gastric bypass hypoglycaemia

    NARCIS (Netherlands)

    Emous, M.; Ubels, F. L.; van Beek, A. P.

    2015-01-01

    In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the

  18. Sen perforation af tyndtarm efter laparoskopisk gastrisk bypass

    DEFF Research Database (Denmark)

    Spanager, Lene; Sigild, Ulf Henrik; Neuenschwander, Anders Ulrich

    2010-01-01

    We present two cases in which the patients were admitted to a local hospital with acute abdominal pain four or five months after having undergone laparoscopic gastric bypass. In both cases, operation revealed a perforation of the small bowel close to the distal anastomosis. In the first case...... bypass but as our two cases illustrate they are important to keep in mind....

  19. Lower leg electrical impedance after distal bypass surgery

    DEFF Research Database (Denmark)

    Belanger, G K; Bolbjerg, M L; Heegaard, N H

    1998-01-01

    Electrical impedance was determined in 13 patients following distal bypass surgery to evaluate lower leg oedema as reflected by its circumference. Tissue injury was assessed by the plasma concentration of muscle enzymes. After surgery, the volume of the control lower leg increased from 1250 (816...... to be a useful method for the evaluation of lower leg oedema after distal bypass surgery....

  20. Inpatient healthcare provider bypassing by women and their ...

    African Journals Online (AJOL)

    Introduction: bypassing refers to a person's decision to seek care at a healthcare facility that is not the nearest one of its type to the person's home. Methods: this study examined inpatient care facility bypassing in urban Bo, Sierra Leone using data from 1,980 women with children 15 years of age and younger who were ...

  1. Reverse bias protected solar array with integrated bypass battery

    Science.gov (United States)

    Landis, Geoffrey A (Inventor)

    2012-01-01

    A method for protecting the photovoltaic cells in a photovoltaic (PV) array from reverse bias damage by utilizing a rechargeable battery for bypassing current from a shaded photovoltaic cell or group of cells, avoiding the need for a bypass diode. Further, the method mitigates the voltage degradation of a PV array caused by shaded cells.

  2. Basics of cardiopulmonary bypass: normal and abnormal postoperative CT appearances.

    Science.gov (United States)

    El-Sherief, Ahmed H; Wu, Carol C; Schoenhagen, Paul; Little, Brent P; Cheng, Allen; Abbara, Suhny; Roselli, Eric E

    2013-01-01

    Cardiothoracic surgical procedures with and without cardiopulmonary bypass are becoming more commonly performed as surgical techniques improve and the population ages. Changes related to cardiopulmonary bypass are often depicted at routine postoperative computed tomographic (CT) studies performed for various reasons. The purpose of this article is to present knowledge critical to the accurate postoperative evaluation of the patient who has undergone cardiopulmonary bypass. This article will review the surgical technique for cardiopulmonary bypass, as well as the associated normal and abnormal postoperative imaging findings. Common cannulation sites used for cardiopulmonary bypass include the ascending aorta, axillary artery, right atrium, superior vena cava, and inferior vena cava. Normal postoperative findings related to cardiopulmonary bypass include (a) felt pledgets, which are used to reinforce cannulation sites; (b) oversewn side grafts; and (c) oversewn graft side branches. These normal postoperative findings can be mistaken for abnormalities. Abnormal postoperative findings related to cardiopulmonary bypass include pseudoaneurysm formation at cannulation sites, aortic dissection, and seroma formation. An awareness of normal and abnormal postoperative CT findings related to cardiopulmonary bypass is critical for all radiologists who interpret chest CT studies, to help prevent unnecessary further evaluation and to help direct prompt treatment when warranted.

  3. Computed tomography perfusion evaluation after extracranial-intracranial bypass surgery

    NARCIS (Netherlands)

    Vos, Pieter C.; Riordan, Alan J.; Smit, Ewoud J.; de Jong, Hugo W. A. M.; van der Zwan, Albert; Velthuis, BK; Viergever, Max A.; Dankbaar, Jan Willem

    Objective: Perfusion imaging is increasingly used for postoperative evaluation of extracranial to intracranial (EC-IC) bypass surgery. Altered hemodynamics and delayed arrival of the contrast agent in the area fed by the bypass can influence perfusion measurement. We compared perfusion asymmetry

  4. What to Expect during Coronary Artery Bypass Grafting

    Science.gov (United States)

    ... an illustration, go to the Health Topics Heart Surgery article. The surgeon will take an artery or vein from your body—for example, from your chest or leg—to use as the bypass graft. For surgeries with several bypasses, both artery and vein grafts ...

  5. Predicting the need for blood during cardiopulmonary bypass

    African Journals Online (AJOL)

    Adele

    infections.1 Furthermore, autologous blood transfusions relieve pres- sure on scarce banked-blood ... delivery that occurs on initiation of cardiopulmonary bypass (CPB). In spite of patient cooling during CPB that ... considered prudent to have blood ready in the operating room at the time of going onto bypass in order to ...

  6. Outcomes of coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    Anna Louise Hawkes

    2006-12-01

    Full Text Available Anna Louise Hawkes1,3, Madeleine Nowak1, Benjamin Bidstrup2, Richard Speare11School of Public Health, Tropical, Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland, Australia (3Currently Queensland Cancer Fund; 2John Flynn Hospital, Gold Coast, Queensland, AustraliaAbstract: This review article summarizes the major studies that have investigated the outcomes of coronary artery bypass graft surgery (CABG. The article includes a review of the literature in the areas of: history of CABG; indications for CABG; and measurement of quality of life following CABG, including prolongation of life, physical functioning (ie, relief from angina and dyspnea, physical activity, as well as complications of surgery and re-hospitalization, psychological functioning, and social functioning. Overall, the literature demonstrates that the outcomes of CABG have historically been measured in terms of mortality and morbidity; however, it has now been well recognized that adjustment to CABG is a multidimensional phenomenon that is not fully explained by medical factors. Therefore, in addition to studying mortality and morbidity outcomes following CABG, many recent studies have identified that it is important to investigate various physical, psychological, and social variables that have a significant impact on post-operative adjustment to CABG. Keywords: coronary artery bypass graft surgery, outcomes, quality of life, recovery

  7. Cardiopulmonary bypass in the pediatric population.

    Science.gov (United States)

    Whiting, David; Yuki, Koichi; DiNardo, James A

    2015-06-01

    Cardiopulmonary bypass (CPB) facilitates the repair of cardiac lesions in adults and children. Surgical mortality has decreased with improvements in technique allowing for the successful repair of complex heart defects in neonates of increasingly low body weight and gestational age. The physiological effects of CPB are more significant in children. The presence of intracardiac shunts and other anatomic variants further complicates CPB in patients with congenital heart disease. Special techniques and monitors are often necessary. Protocols are often established within individual institutions to standardize the approach to CPB. The anesthesiologist caring for the patient must understand the physiology of CPB to facilitate the initiation and separation from bypass, and to be able to treat complications. Evidence supporting a particular technique of CPB in pediatric population is still largely from uncontrolled or nonrandomized trials, observational studies, extrapolation from adult studies, and expert opinion. The heterogeneity of congenital heart disease makes randomized controlled trials or meta-analyses challenging, and thus they are limited in the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. KEEFEKTIFAN PAIRED STORYTELLING DAN JIGSAW DALAM PENINGKATAN KOMPETENSI BERBICARA SISWA KELAS VIII SMP NEGERI 3 SLEMAN

    Directory of Open Access Journals (Sweden)

    Nurmiyati Nurmiyati

    2014-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui: (1 apakah ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, dan konvensional dalam meningkatkan kompetensi berbicara siswa, (2 teknik pembelajaran berbicara yang paling efektif antara ketiga teknik penelitian itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman. Penelitian ini menggunakan jenis penelitian eksperimen semu dengan nonequivalent control-group design. Hasil penelitian menunjukkan bahwa: (1 Ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, and konvensional itu dalam meningkatkan kompetensi berbicara siswa dengan nilai F sebesar 3,532 dan signifikan dengan P < 0,05, yaitu sebesar 0,033, dan (2 teknik paired storytelling adalah teknik keterampilan berbicara yang paling efektif diantara ketiga teknik itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman dengan mean tertinggi sebesar 74,3492. Kata kunci: teknik paired storytelling, teknik jigsaw, teknik konvensional, kompetensi berbicara

  9. Genomic characterisation of the toxin Amm VIII from the scorpion Androctonus mauretanicus mauretanicus.

    Science.gov (United States)

    Alami, Meriem; Céard, Brigitte; Legros, Christian; Bougis, Pierre E; Martin-Eauclaire, Marie-France

    2006-04-01

    The genomic DNA sequence encoding the scorpion toxin Amm VIII was amplified from genomic DNA of the scorpion Androctonus mauretanicus mauretanicus from Morocco, subcloned and sequenced. An intron, with a high A+T content (73.5%), split a Gly codon at the end of the precursor signal peptide and the consensus GT/AG splice junction was identified in the Amm VIII gene. This intron of only 166 bp is the smallest intron described so far for a long-chain scorpion toxin gene. In addition, this study led to the identification of three new toxin-related genes. From the deduced amino acid sequences of the encoded precursor proteins, we found that the mature putative toxins were highly similar to the scorpion toxins Leiurus quinquestriatus quinquestriatus IV and Odonthobuthus doriae 1.

  10. Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    2013-01-01

    Full Text Available Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs. An indirect intracellular staining (ICS method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels.

  11. Pengembangan Modul Matematika Untuk Pembelajaran Berbasis Masalah (Problem Based Learning) Pada Materi Pokok Persamaan Garis Lurus Kelas VIII SMP

    OpenAIRE

    Khayati, Fitrotul; Sujadi, Imam; Sari Saputro, Dewi Retno

    2016-01-01

    Absrtact:The objectives of this research were to investigate: (1) how to develop of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School; and (2) the effectiveness of result of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School. This research consisted of two phases. The fi...

  12. Cardiopulmonary bypass: development of John Gibbon's heart-lung machine.

    Science.gov (United States)

    Passaroni, Andréia Cristina; Silva, Marcos Augusto de Moraes; Yoshida, Winston Bonetti

    2015-01-01

    To provide a brief review of the development of cardiopulmonary bypass. A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation. The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies. Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function.

  13. IMPLEMENTASI PENDEKATAN KONFLIK KOGNITIF DALAM PEMBELAJARAN FISIKA UNTUK MENUMBUHKAN KEMAMPUAN BERPIKIR KRITIS SISWA SMP KELAS VIII

    OpenAIRE

    A. Setyowati; B. Subali; Mosik -

    2012-01-01

    Tujuan dari penelitian ini adalah untuk mengetahui pengaruh implementasi pendekatan konflik kognitif dalam pembelajaran fisikapokok bahasan tekanan pada siswa kelas VIII terhadap kemampuan berpikir kritis, pemahaman konsep dan hasil belajar kognitifsiswa. Penelitian ini merupakan penelitian eksperimen. Setelah dilakukan pengambilan sampel secara random sampling,diperoleh kelas VIIIB sebagai kelas eksperimen dan kelas VIIIC sebagai kelas kontrol. Dari analisis uji rata-rata dua pihak atau uji ...

  14. Construction of a mouse model of factor VIII deficiency by gene targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  15. Historical intensity VIII earthquakes along the Rhone valley (Valais, Switzerland): primary and secondary effects

    Energy Technology Data Exchange (ETDEWEB)

    Fritsche, S.; Faeh, D.; Schwarz-Zanetti, G.

    2012-06-15

    In recent years the upper Rhone Valley has been one of the most intensively investigated regions by the Swiss Seismological Service. The high seismicity in the region encourages research in the seismological field and one main focus has been historical seismology. This report presents the state of the art of our historical investigations by giving an overview of the effects of four damaging earthquakes with intensity larger than VII, for which a fairly large number of documents could be found and analyzed. The overview includes the events of 1584 (Aigle, epicentral intensity VIII), 1755 (Brig, epicentral intensity VIII), 1855 (Visp, epicentral intensity VIII), and 1946 (Sierre, epicentral intensity VIII for the main shock and intensity VII for the largest aftershock). The paper focuses mainly on primary and secondary effects in the epicentral region, providing the key data and a general characterization of the event. Generally, primary effects such as the reaction of the population and impact on buildings took more focus in the past. Thus building damage is more frequently described in historic documents. However, we also found a number of sources describing secondary effects such as landslides, snow avalanches, and liquefaction. Since the sources may be useful, we include citations of these documents. The 1584 Aigle event, for example, produced exceptional movements in the Lake of Geneva, which can be explained by an expanded sub aquatic slide with resultant tsunami and seiche. The strongest of the aftershocks of the 1584 event triggered a destructive landslide covering the villages Corbeyrier and Yvorne, Vaud. All macroseismic data on the discussed events are accessible through the web page of the Swiss Seismological Service (http://www.seismo.ethz.ch). (authors)

  16. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia

    OpenAIRE

    Sejersted, Yngve; Hildrestrand, Gunn A.; Kunke, David; Rolseth, Veslemøy; Krokeide, Silje Z.; Neurauter, Christine G.; Suganthan, Rajikala; Atneosen-Åsegg, Monica; Fleming, Aaron M.; Saugstad, Ola D.; Burrows, Cynthia J.; Luna, Luisa; Bjørås, Magnar

    2011-01-01

    Neural stem/progenitor cell proliferation and differentiation are required to replace damaged neurons and regain brain function after hypoxic-ischemic events. DNA base lesions accumulating during hypoxic-ischemic stress are removed by DNA glycosylases in the base-excision repair pathway to prevent cytotoxicity and mutagenesis. Expression of the DNA glycosylase endonuclease VIII-like 3 (Neil3) is confined to regenerative subregions in the embryonic and perinatal brains. Here we show profound n...

  17. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Boyko, Konstantin M., E-mail: kmb@inbi.ras.ru [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Gorbacheva, Marina A.; Korzhenevskiy, Dmitry A. [National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Alekseeva, Maria G.; Mavletova, Dilara A.; Zakharevich, Natalia V.; Elizarov, Sergey M.; Rudakova, Natalia N.; Danilenko, Valery N. [Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow, 119333 (Russian Federation); Popov, Vladimir O. [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation)

    2016-09-02

    Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3′-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray diffraction method with a resolution of 2.15 Å. Deep analysis of APHVIII structure and its comparison with known structures of aminoglycoside phosphotransferases of various types reveals that AphVIII has a typical two-domain fold and, however, possesses some unique characteristics that distinguish the enzyme from its known homologues. The most important difference is the presence of the activation loop with unique Ser146 residue. We demonstrate that in the apo-state of the enzyme the activation loop does not interact with other parts of the enzyme and seems to adopt catalytically competent state only after substrate binding. - Highlights: • 3D structure of the novel aminoglycoside phosphotransferase AphVIII was obtained. • AphVIII activation loop is clearly identified in the electron density. • AphVIII has some unique structural features in its substrate C-ring binding pocket.

  18. The impact of haemodilution and bypass pump flow on cerebral oxygen desaturation during cardiopulmonary bypass--A comparison of two systems of cardiopulmonary bypass.

    Science.gov (United States)

    Bennett, M J; Weatherall, M; Webb, G; Dudnikov, S F; Lloyd, C T

    2015-07-01

    To determine the influence of haemodilution, bypass flow rates and calculated oxygen delivery during cardiopulmonary bypass (CPB) with either a conventional CPB (C-CPB) circuit or a miniaturised (Mini-CPB) circuit on cerebral oxygen desaturation. The effect of minimal haemodilution with a Mini-CPB was investigated. Eighty patients scheduled for elective cardiac surgery. Oxygenated haemoglobin (O2Hb) and tissue oxygenation index (TOI) were measured with near-infrared spectroscopy (NIRS). The average indexed bypass pump flow was significantly lower with Mini-CPB. When combined with haemoglobin concentration, the average oxygen delivery was the same between groups. Patients in the C-CPB group had a greater duration and severity of cerebral desaturation to a level bypass, whereas desaturation with Mini-CPB was associated with low perioperative haemoglobin concentration. © The Author(s) 2014.

  19. [Structure and function of the factor VIII/von Willebrand factor complex].

    Science.gov (United States)

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  20. Can pregnant women be safely placed on cardiopulmonary bypass?

    Science.gov (United States)

    Sepehripour, Amir H; Lo, Tammy T; Shipolini, Alex R; McCormack, David J

    2012-12-01

    A best evidence topic was written according to a structured protocol. The question addressed was whether cardiopulmonary bypass can be used safely with satisfactory maternal and foetal outcomes in pregnant patients undergoing cardiac surgery. A total of 679 papers were found using the reported searches of which 14 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were maternal and foetal mortality and complications, mode of delivery, cardiopulmonary bypass and aortic cross-clamp times, perfusate flow rate and temperature and maternal NYHA functional class. The most recent of the best evidence studies, a retrospective observational study of 21 pregnant patients reported early and late maternal mortalities of 4.8 and 14.3%, respectively, and a foetal mortality of 14.3%. Median cardiopulmonary bypass and aortic cross-clamp times were 53 and 35 min, respectively, and the median bypass temperature was 37°C. Three larger retrospective reviews of the literature reported maternal mortality rates of 2.9-5.1% and foetal mortality rates of 19-29%. Mean cardiopulmonary bypass times ranged from 50.5 to 77.8 min. Another retrospective observational study reported maternal mortality of 13.3% and foetal mortality of 38.5%. Mean cardiopulmonary bypass and aortic cross-clamp times were 89.1 and 62.8 min, respectively, with a mean bypass temperature of 31.8°C. A retrospective case series reported no maternal mortality and one case of foetal mortality. Median cardiopulmonary bypass and aortic cross-clamp times were 101 and 88 min, respectively. Eight case reports described 10 patients undergoing cardiopulmonary bypass. There were no reports of maternal mortality and one report of foetal mortality. Mean cardiopulmonary bypass and aortic cross-clamp times were 105 and 50 min, respectively. We conclude that while the use of cardiopulmonary bypass

  1. Low serum sodium level during cardiopulmonary bypass predicts increased risk of postoperative stroke after coronary artery bypass graft surgery.

    Science.gov (United States)

    Munoz, Elizandro; Briggs, Holly; Tolpin, Daniel A; Lee, Vei-Vei; Crane, Terry; Elayda, Macarthur A; Collard, Charles D; Pan, Wei

    2014-04-01

    Rapid decreases in serum sodium levels are associated with altered mental status, seizures, and coma. During cardiac surgery, serum sodium levels decrease rapidly when cardiopulmonary bypass is initiated because cardiopulmonary bypass causes hemodilution. However, whether this decrease influences neurologic outcome after cardiac surgery remains unclear. We investigated whether the average serum sodium level during cardiopulmonary bypass is independently predictive of postoperative stroke or 30-day all-cause mortality in patients who undergo primary coronary artery bypass grafting. In a single-institution, retrospective cohort of 2348 consecutive patients who underwent primary, isolated coronary artery bypass grafting, sequential multivariate logistic regression was performed to determine the threshold below which the average serum sodium level during cardiopulmonary bypass independently predicts postoperative stroke or early death. To further test the validity of this threshold and to control for selection bias, stepwise multivariate logistic regression was also performed on propensity score-matched patients (n = 924). An average serum sodium level less than 130 mEq/L during cardiopulmonary bypass was independently predictive of stroke, both in the entire study cohort (1.44% vs 2.92%; odds ratio, 2.09; 95% confidence interval, 1.1-4.1; P = .03) and in the propensity-matched patients (0.9% vs 3.0%; odds ratio, 4.1; 95% confidence interval, 1.3-13.0; P = .02). The average serum sodium level during cardiopulmonary bypass was not independently associated with early death, regardless of what threshold value was used. An average serum sodium level of less than 130 mEq/L during cardiopulmonary bypass is independently associated with an increased risk of postoperative stroke in patients who undergo primary coronary artery bypass grafting. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  2. PENINGKATAN PEMBELAJARAN MENULIS PUISI BEBAS MELALUI MEDIA LAGU MEDLEY SISWA KELAS VIII SMP SINTANG

    Directory of Open Access Journals (Sweden)

    Rohanawati Silalahi

    2015-05-01

    Full Text Available Penelitian ini bertujuan untuk meningkatkan pembelajaran menulis puisi bebas melalui media lagu medley siswa kelas VIII B SMP Sintang. Subjek penelitian adalah siswa kelas VIII B SMP Sintang. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK. Prosedur pelaksanaan dan implementasi penelitian dilaksanakan dalam dua siklus. Teknik pengumpulan data berupa obsevasi, wawancara, catatan lapangan, angket, evaluasi dan dokumentasi. Instrumen pengumpulan data meliputi lembar wawancara, lembar catatan lapangan, lembar angket, lembar tes hasil belajar dan lembar portofolio serta dokumentasi foto kegiatan. Teknik analisis data yang digunakan adalah analisis data kuantitatif dan kualitatif. Hasil penelitian ini menunjukkan bahwa penggunaan media lagu medley dapat meningkatkan pembelajaran menulis puisi bebas. Peningkatan hasil atau produk dapat dilihat dari perbandingan skor rata-rata keterampilan menulis puisi bebas siswa pada setiap siklus. Nilai rata-rata siswa pada tahap pratindakan adalah 55,23, pada saat siklus I meningkat menjadi 71,18, dan pada siklus II meningkat menjadi 73,4. ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ DEVELOPING THE TEACHING OF FREE VERSE WRITING THROUGH MEDLEY SONG MEDIA TO GRADE VIII STUDENTS OF SMP SINTANG   Abstract This study aims to improve the teaching of free verse writing through medley song media to Grade VIII B students of SMP Sintang. The research subjects were Grade VIII B students of SMP Sintang,. This was a classroom action research (CAR. The research procedure and implementation were conducted in two cycles. The data were collected through observations, field notes, questionnaires, evaluations, and documentations. The data collecting instruments included interview sheets, field note sheets

  3. Genetic factors influencing inhibitor development in a cohort of South African haemophilia A patients.

    Science.gov (United States)

    Lochan, A; Macaulay, S; Chen, W C; Mahlangu, J N; Krause, A

    2014-09-01

    A critical complication of factor VIII (FVIII) replacement therapy in Haemophilia A (HA) treatment is inhibitor development. Known genetic factors predisposing to inhibitor development include FVIII (F8) gene mutations, ethnicity, a family history of inhibitors and FVIII haplotype mismatch. The aim of this study was to characterize and correlate these genetic factors in a cohort of South African HA patients. This was a retrospective study that included 229 patients and involved the analysis of patient files, HA molecular and clinical databases and molecular analysis of the F8 gene haplotype. Of the 229 patients, 51% were of black ethnicity, 49% were white, 5% had mild HA, 4% were moderate and 91% were severe, 36% were int22 positive and 13% were inhibitor positive. Of the inhibitor positive patients, 72% were black patients. Inhibitors were reported in 27% of black int22 positive patients, 13% of black int22 negative patients, 9% of white int22 positive patients and 7% of white int22 negative. The H1 haplotype was more common in whites (75%) and H2 was more common in blacks (74%). H3 and H5 were only found in black patients and had a higher frequency of inhibitor development than H1 and H2. In this small HA cohort, black patients had a significantly higher frequency of inhibitor development and the results were indicative of an association between inhibitor development, ethnicity and haplotype. © 2014 John Wiley & Sons Ltd.

  4. Laparoscopic Conversion of One Anastomosis Gastric Bypass to a Standard Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Amor, Imed Ben; Petrucciani, Niccolo; Kassir, Radwan; Al Munifi, Abdullah; Piche, Thierry; Debs, Tarek; Gugenheim, Jean

    2017-05-01

    One anastomosis gastric bypass (OAGB) demonstrated results similar to traditional Roux-en-Y procedures [1-3], in terms of weight loss and resolution of obesity-related comorbidities. The main controversy regarding OAGB is the concern for an association between biliary alkaline gastritis and esophageal or gastric cancer raised by some studies [4]. We present the case of a 51-year-old woman with a BMI of 41 kg/m2 who underwent a laparoscopic OAGB in 2014. One year later, she consulted for recurrent heartburns. An upper GI endoscopy showed pouchitis and bile reflux in the esophagus. Medical treatment of gastroesophageal reflux disease was ineffective. We decided to convert the OAGB to a Roux-en-Y gastric bypass (RYGB). In this video, we show how to revise an OAGB to treat chronic bile reflux, by converting the procedure to a standard RYGB. The intervention starts by restoring the normal anatomy of the small bowel, with the resection of the gastrojejunal anastomosis, which was located at 250-cm du Treitz's ligament. Then, the gastric pouch is created. A standard Roux-en-Y gastric bypass is performed. The resection of the gastrojejunal anastomosis allows fashioning the Roux-en-Y limb with the classical measures. This technique allows a conversion to a standard RYGB and is effective in treating the biliary reflux.

  5. Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

    Science.gov (United States)

    Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

    2015-04-01

    Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

  6. Recent Advances in Pediatric Cardiopulmonary Bypass.

    Science.gov (United States)

    McRobb, Craig M; Mejak, Brian L; Ellis, W Cory; Lawson, D Scott; Twite, Mark D

    2014-06-01

    There have been numerous recent advances geared specifically toward the practice of pediatric cardiopulmonary bypass (CPB). These advances include the development of the first oxygenator intended solely for the neonatal CPB patient; pediatric oxygenators with low prime volumes and surface areas, which allow flows up to 2 L/min; pediatric oxygenators with integrated arterial filters; and miniature ultrafiltration (UF) devices, which allow for high rates of ultrafiltrate removal. When used in combination with heart lung machines with mast-mounted pumps, these advances can result in significant decreases in CPB circuit surface areas and prime volumes. This may attenuate CPB-associated hemodilution and decrease or eliminate the need for homologous red blood cells during or after CPB. In addition to these equipment-related advances, changes in myocardial protection strategies and the technique of modified UF as it relates to these advances are discussed. © The Author(s) 2014.

  7. Emergent cardiopulmonary bypass during pectus excavatum repair

    Directory of Open Access Journals (Sweden)

    Ryan Craner

    2013-01-01

    Full Text Available Pectus excavatum is a chest wall deformity that produces significant cardiopulmonary disability and is typically seen in younger patients. Minimally invasive repair of pectus excavatum or Nuss procedure has become a widely accepted technique for adult and pediatric patients. Although it is carried out through a thoracoscopic approach, the procedure is associated with a number of potential intraoperative and post-operative complications. We present a case of cardiac perforation requiring emergent cardiopulmonary bypass in a 29-year-old male with Marfan syndrome and previous mitral valve repair undergoing a Nuss procedure for pectus excavatum. This case illustrates the importance of vigilance and preparation by the surgeons, anesthesia providers as well as the institution to be prepared with resources to handle the possible complications. This includes available cardiac surgical backup, perfusionist support and adequate blood product availability.

  8. Ultra by-pass ratio engine

    Energy Technology Data Exchange (ETDEWEB)

    Endo, Masanori; Sugiyama, Shichihisa

    1986-12-10

    A engine where ratio of fan's or propeller's air flow rate to air flow rate through engine combustion chamber is more than 15 is generally named the ultra bypass ratio engine (UBE). This engine employs the exhaust gas from the engine separately to the fan or propeller and jet nozzle exhaust to obtain higher total thrust efficiency. The increase rate of thrust by using UBE is equal to the improvement rate of fuel comsumption. Much efforts are continuously made to develop UBE toward the 21 century by many companies and it is necessary to develop the core engine of high specific output and high heat efficiency, and variable pitch / high aspect ratio fan or propeller and to reseach the integrated system technology. (5 refs, 9 figs)

  9. Impact of Norepinephrine on Regional Cerebral Oxygenation During Cardiopulmonary Bypass.

    Science.gov (United States)

    Hagen, Ove Andreas; Høiseth, Lars Øivind; Roslin, André; Landsverk, Svein Aslak; Woldbaek, Per Reidar; Pripp, Are Hugo; Hanoa, Rolf; Kirkebøen, Knut Arvid

    2016-04-01

    Norepinephrine is used to increase mean arterial pressure during cardiopulmonary bypass. However, it has been suggested that norepinephrine could constrict cerebral arteries, reducing cerebral blood flow. The aim of this study, therefore, was to explore whether there was an association between doses of norepinephrine to maintain mean arterial pressure at ≈80 mmHg during cardiopulmonary bypass and cerebral oxygen saturation measured using near-infrared spectroscopy. Observational study. University hospital. Patients undergoing cardiac surgery (n = 45) using cardiopulmonary bypass. Norepinephrine was administered to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass. From initiation of cardiopulmonary bypass to removal of the aortic cross-clamp, norepinephrine dose, mean arterial pressure, partial pressure of arterial carbon dioxide, partial pressure of arterial oxygen, hemoglobin, and pump flow values were averaged over 1 minute, giving a total of 3,460 data points entered as covariates in a linear mixed model for repeated measurements, with cerebral oxygen saturation measured using near-infrared spectroscopy as outcome. There was no statistically significant association between norepinephrine dose to maintain mean arterial pressure and cerebral oxygen saturation (p = 0.46) in this model. Administration of norepinephrine to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass was not associated with statistically significant changes in cerebral oxygen saturation. These results indicated that norepinephrine could be used to increase mean arterial pressure during cardiopulmonary bypass without reducing cerebral oxygen saturation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A Study of Hydraulic Resistance of Viscous Bypass Gap in Magnetorheological Damper

    Directory of Open Access Journals (Sweden)

    Michal Kubík

    2016-01-01

    Full Text Available The paper presents hydraulic resistance of viscous bypass hole in magnetorheological damper. The suitable design of bypass hole is essential for efficient function of MR damper in automotive industry. In the paper analytical hydraulic model of bypass gap is compared with experiments. The commonly used hydraulic model of bypass gap does not agree with experiments.

  11. Off-pump versus on-pump coronary artery bypass grafting for ischaemic heart disease

    DEFF Research Database (Denmark)

    Møller, Christian H; Penninga, Luit; Wetterslev, Jørn

    2012-01-01

    Coronary artery bypass grafting (CABG) is performed both without and with cardiopulmonary bypass, referred to as off-pump and on-pump CABG respectively. However, the preferable technique is unclear.......Coronary artery bypass grafting (CABG) is performed both without and with cardiopulmonary bypass, referred to as off-pump and on-pump CABG respectively. However, the preferable technique is unclear....

  12. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line... entitled “Guidance for Cardiopulmonary Bypass Arterial Line Blood Filter 510(k) Submissions.” [45 FR 7907...

  13. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma.

    Science.gov (United States)

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup

    2008-05-01

    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

  14. Asendan Desendan Aortic Bypass: Atan Kalpte Mediyan Sternotomi Yoluyla Onarim

    Directory of Open Access Journals (Sweden)

    Muhammet Akyuz

    2013-10-01

    Full Text Available We report the case of a 9-month-old patient presenting for redo aortic arch surgery because of recoarctation. In present case, ascending-to-descending aortic bypass via median sternotomy was performed without cardiopulmonary bypass with good result. In spite of the fact that the different surgical and intervention treatment options of aortic coarctation are quite satisfactory, a certain group of patients need reoperation because of recoarctation. The recoarctation repair of the aorta with the extra-anatomic aortic bypass is considered a low-risk procedure with high success rate.

  15. Linitis plastica of the bypassed stomach 7 years after Roux-en-Y gastric bypass: a case report.

    Science.gov (United States)

    Haenen, Filip Wn; Gys, Ben; Moreels, Tom; Michielsen, Maartje; Gys, Tobie; Lafullarde, Thierry

    2017-10-24

    Laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the preferred surgical procedure to treat morbid obesity. It has proven its effects on excess weight loss and its positive effect on comorbidities. One of the main issues, however, is the post-operative evaluation of the bypassed gastric remnant. In literature, cancer of the excluded stomach after RYGB is rare. We describe the case of a 52-year-old woman with gastric linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass, diagnosed by means of laparoscopy and Single-Balloon enteroscopy, and it is clinical importance. Linitis plastica of the excluded stomach after RYGB is a very rare entity. This case report shows the importance of long-term post-operative follow-up, and the importance of single-balloon enteroscopy for visualization of the bypassed stomach remnant, when other investigations remain without results. This case report is only the second report of a linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass.

  16. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    DEFF Research Database (Denmark)

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...... showed impaired capacity for acidification of urine. The lowest urinary pH was 5.53 +/- 0.10 in 10 bypass patients and 4.76 +/- 0.06 in 6 controls. The corresponding values for standard bicarbonate in plasma were 15.0 +/- 0.3 mM and 15.8 +/- 0.3 mM. Glomerular filtration rate was identical in the two...... groups. Fractional loss of bicarbonate in urine was higher in controls than in bypass patients. The renal impairment is classified as distal renal tubular acidosis....

  17. Evaluation of bypass lane safety, operations, and design in Kansas.

    Science.gov (United States)

    2015-08-01

    The construction of bypass lanes at rural intersections has typically been considered a low-cost highway safety : improvement by the transportation community. However, this needs to be quantitatively evaluated so that decisions can be made : on wheth...

  18. Antiplatelet therapy at the time of coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Kremke, Michael; Jensen, Mariann Tang; Bak, Mikkel

    2013-01-01

    OBJECTIVES: The purpose of this multicentre cohort study was to examine the relationship between antiplatelet therapy (APT) at the time of coronary artery bypass grafting (CABG) and postoperative bleeding complications, transfusion requirements and adverse cardiovascular events. METHODS: A matched...

  19. Subarachnoid-subarachnoid bypass for spinal adhesive arachnoiditis.

    Science.gov (United States)

    Tachibana, Toshiya; Moriyama, Tokuhide; Maruo, Keishi; Inoue, Shinichi; Arizumi, Fumihiro; Yoshiya, Shinichi

    2014-11-01

    The authors report a case of adhesive arachnoiditis (AA) and arachnoid cyst successfully treated by subarachnoid to subarachnoid bypass (S-S bypass). Arachnoid cysts or syringes sometimes compress the spinal cord and cause compressive myelopathy that requires surgical treatment. However, surgical treatment for AA is challenging. A 57-year-old woman developed leg pain and gait disturbance. A dorsal arachnoid cyst compressed the spinal cord at T7-9, the spinal cord was swollen, and a small syrinx was present at T9-10. An S-S bypass was performed from T6-7 to T11-12. The patient's gait disturbance resolved immediately after surgery. Two years later, a small arachnoid cyst developed. However, there was no neurological deterioration. The myelopathy associated with thoracic spinal AA, subarachnoid cyst, and syrinx improved after S-S bypass.

  20. Rodent models of cardiopulmonary bypass: utility in improving perioperative outcomes

    NARCIS (Netherlands)

    de Lange, F.

    2008-01-01

    Despite advances in surgical and anesthesia techniques, subtle neurologic injury still remains an important complication after cardiac surgery. Because the causes are multifactorial and complex, research in an appropriate small animal model for cardiopulmonary bypass (CPB) is warranted. This thesis

  1. Oil Bypass Filter Technology Performance Evaluation - January 2003 Quarterly Report

    Energy Technology Data Exchange (ETDEWEB)

    Laurence R. Zirker; James E. Francfort

    2003-01-01

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  2. Oil Bypass Filter Technology Performance Evaluation - First Quarterly Report

    Energy Technology Data Exchange (ETDEWEB)

    Zirker, L.R.; Francfort, J.E.

    2003-01-31

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  3. Stressors and anxiety in patients undergoing coronary artery bypass surgery

    National Research Council Canada - National Science Library

    Gallagher, Robyn; McKinley, Sharon

    2007-01-01

    Patients undergoing coronary artery bypass surgery who have increased anxiety levels have poorer outcomes than patients with lower levels, yet few studies have identified the concerns associated with this anxiety...

  4. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  5. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  6. AKTIVITAS FISIK, ASUPAN ENERGI DAN STATUS GIZI WANITA PEMETIK TEH DI PTPN VIII BANDUNG, JAWA BARAT

    Directory of Open Access Journals (Sweden)

    Venny Agustiani Mahardikawati

    2012-03-01

    Full Text Available 800x600 Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Quality of human resources is very important to improve productivity. The worker productivity is correlated with nutritional status and health status. The objective of the research is to analyze physical activity, energy intake, nutritional status, of women workers at Tea Plantation PTPN VIII Bandung, West Java. The cross sectional design was used in this study to elaborate physical activity, nutritional status, and productivity of tea picker’s women. The criteria of study sample were tea picker’s women at cluster area of Malabar tea plantation of PTPN VIII Bandung, having infant and they were willing to be interviewed. The total number of 92 women sample was chosen randomly. Primary data consisted of physical activity recall (2x24 hours, food consumption recall (2x24 hours, anthropometry data (weight and height, and productivity (passage of tea sprout. Secondary data were included data of PT Perkebunan Nusantara VIII Bandung, West Java. The result showed that more than a half of samples having active or moderate physical activity level (PAL. The physical activity level of samples during work day (average PAL=1.87 was higher than holiday (average PAL=1.69 (p2362 kcal and 2134 kcal. The average energy adequacy level during workday and day off according to Schofield and Oxford equation were not significantly different, respectively 97,2% and 103,3%. The majority of samples had normal nutritional status, and 30.4% of the sample was overweight. The energy adequacy level according to Schofield and Oxford equation are related to nutritional status of women workers. Keywords: physical activity, energy expenditure, nutritional status, plantation women

  7. Transfusion requirements in elective cardiopulmonary bypass surgery patients

    DEFF Research Database (Denmark)

    Sivapalan, Praleene; Bäck, Anne Caroline; Ostrowski, Sisse Rye

    2017-01-01

    Managing haemostasis in patients undergoing cardiopulmonary bypass (CPB) surgery remains a challenge. There is no established laboratory test to predict transfusion requirements in cardiac surgery. We investigated whether preoperative Thromboelastography (TEG) with Platelet Mapping Assay (PMA......) or Multiple Electrode Aggrometry (MEA) could predict transfusion requirements in patients undergoing elective coronary artery bypass grafting (CABG) or combined CABG with aortic or mitral valve replacement. We prospectively investigated 199 patients undergoing elective CABG or combined procedures. PMA and MEA...

  8. Hypoparathyroidism after total thyroidectomy in patients with previous gastric bypass.

    Science.gov (United States)

    Droeser, Raoul A; Ottosson, Johan; Muth, Andreas; Hultin, Hella; Lindwall-Åhlander, Karin; Bergenfelz, Anders; Almquist, Martin

    2017-03-01

    Case reports suggest that patients with previous gastric bypass have an increased risk of severe hypocalcemia after total thyroidectomy, but there are no population-based studies. The prevalence of gastric bypass before thyroidectomy and the risk of hypocalcemia after thyroidectomy in patients with previous gastric bypass were investigated. By cross-linking The Scandinavian Quality Registry for Thyroid, Parathyroid and Adrenal Surgery with the Scandinavian Obesity Surgery Registry patients operated with total thyroidectomy without concurrent or previous surgery for hyperparathyroidism were identified and grouped according to previous gastric bypass. The risk of treatment with intravenous calcium during hospital stay, and with oral calcium and vitamin D at 6 weeks and 6 months postoperatively was calculated by using multiple logistic regression in the overall cohort and in a 1:1 nested case-control analysis. We identified 6115 patients treated with total thyroidectomy. Out of these, 25 (0.4 %) had undergone previous gastric bypass surgery. In logistic regression, previous gastric bypass was not associated with treatment with i.v. calcium (OR 2.05, 95 % CI 0.48-8.74), or calcium and/or vitamin D at 6 weeks (1.14 (0.39-3.35), 1.31 (0.39-4.42)) or 6 months after total thyroidectomy (1.71 (0.40-7.32), 2.28 (0.53-9.75)). In the nested case-control analysis, rates of treatment for hypocalcemia were similar in patients with and without previous gastric bypass. Previous gastric bypass surgery was infrequent in patients undergoing total thyroidectomy and was not associated with an increased risk of postoperative hypocalcemia.

  9. Association of sex with patency of femorodistal bypass grafts

    DEFF Research Database (Denmark)

    Watson, H R; Schroeder, T V; Simms, M H

    2000-01-01

    There is evidence for superior patency in infra-inguinal bypass procedures in men compared to women. A large, prospectively planned series was investigated in order to confirm this finding and to determine the origin of this difference in outcome.......There is evidence for superior patency in infra-inguinal bypass procedures in men compared to women. A large, prospectively planned series was investigated in order to confirm this finding and to determine the origin of this difference in outcome....

  10. Pharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation

    OpenAIRE

    Wang, Yuming; Jones-Tabah, Jace; Chakravarty, Probir; Stewart, Aengus; Muotri, Alysson; Laposa, Rebecca?R.; Svejstrup, Jesper?Q.

    2016-01-01

    Summary Cockayne syndrome (CS) is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB) affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9), a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Import...

  11. Cancer Incidence and Mortality After Gastric Bypass Surgery

    OpenAIRE

    Adams, Ted D.; Stroup, Antoinette M.; Gress, Richard E.; Adams, Kenneth F.; Calle, Eugenia E; Smith, Sherman C.; Halverson, R. Chad; Simper, Steven C.; Hopkins, Paul N; Hunt, Steven C.

    2009-01-01

    Despite weight loss recommendations to prevent cancer, cancer outcome studies after intentional weight loss are limited. Recently, reduced cancer mortality following bariatric surgery has been reported. This study tested whether reduced cancer mortality following gastric bypass was due to decreased incidence. Cancer incidence and mortality data through 2007 from the Utah Cancer Registry (UCR) were compared between 6,596 Utah patients who had gastric bypass (1984–2002) and 9,442 severely obese...

  12. Boundary-Layer Bypass Transition Over Large-Scale Bodies

    Science.gov (United States)

    2016-12-16

    AFRL-AFOSR-UK-TR-2017-0007 Boundary - layer bypass transition over large-scale bodies Pierre Ricco UNIVERSITY OF SHEFFIELD, DEPARTMENT OF PSYCHOLOGY...REPORT TYPE Final 3. DATES COVERED (From - To) 01 Sep 2013 to 31 Aug 2016 4. TITLE AND SUBTITLE Boundary - layer bypass transition over large-scale...shape of the streamwise velocity profile compared to the flat-plate boundary layer . The research showed that the streamwise wavenumber plays a key role

  13. Combined coronary artery bypass surgery and abdominal aortic aneurysm repair.

    OpenAIRE

    Black, J J; Desai, J B

    1995-01-01

    The proper management of patients with asymptomatic abdominal aortic aneurysms and significant coexistent coronary artery disease is still debatable. The most common approach has been to perform the coronary artery bypass surgery some weeks before the abdominal aortic aneurysm repair in the hope of reducing the cardiac morbidity and mortality. We report our initial experience of three consecutive elective cases where the coronary artery bypass surgery and the abdominal aortic aneurysm repair ...

  14. Robotically assisted totally endoscopic coronary artery bypass surgery

    OpenAIRE

    Canale, Leonardo Secchin; Mick, Stephanie; Mihaljevic, Tomislav; Nair, Ravi; Bonatti, Johannes

    2013-01-01

    Robotically assisted totally endoscopic coronary artery bypass surgery has emerged as a feasible and efficient alternative to conventional full sternotomy coronary artery bypass graft surgery in selected patients. This minimally invasive approach using the daVinci robotic system allows fine intrathoracic maneuvers and excellent view of the coronary arteries. Both on-pump and off-pump operations can be performed to treat single and multivessel disease. Hybrid approaches have the potential of o...

  15. IMPLIKASI YURIDIS PUTUSAN MK NOMOR 46/PUU- VIII/ 2010 TERHADAP AKTA KELAHIRAN ANAK LUAR KAWIN

    Directory of Open Access Journals (Sweden)

    Djumikasih Djumikasih

    2014-08-01

    Full Text Available Abstract This paper aims to identify and analyze what the juridical implications of the publication of the decision of the Constitutional Court No. 46/PUU-VIII / 2010 on Child Outside Marriage Deed which has been published by the Department of Population and Civil Registration prior to the establishment of the Constitutional Court's decision . The method used in this study is a normative juridical approach legislation. From the discussion, it can be concluded that the Constitutional Court 46/PUU-VIII/2010 Number of Tests on Article 43 paragraph ( 1 Marriage Act ( Act No. 1 of 1974 when viewed from the angle of legal certainty it will lead to legal certainty . But the decision will not have any juridical implications of the child's birth certificate that has been published outside of marriage and illegitimate child who was born before the date of February 17, 2012, as if enacted would be contrary to the principle of legality is interpreted Article 47 of the Law on the Constitutional Court and Article 28 ( i of the 1945 Constitution . Likewise, if the terms of the fairness and usefulness , especially for justice seekers / applicant , the timing of this decision is not fair and not useful , because although the Court granted the petition but the Constitutional Court can not be applied to her .   Key words: yuridical implication, birth certificate, children who are born outside of marriage   Abstrak   Tulisan ini bertujuan untuk mengetahui dan menganalisis apa implikasi yuridis dari terbitnya putusan MK Nomor 46/PUU-VIII/ 2010 terhadap Akta Anak Luar Kawin yang sudah diterbitkan oleh Dinas Kependudukan dan Catatan Sipil sebelum lahirnya putusan MK tersebut. Metode yang digunakan dalam penelitian ini adalah yuridis normative dengan pendekatan perundang-undangan. Dari pembahasan dapat disimpulkan bahwa Putusan MK Nomer 46/PUU-VIII/2010 tentang Pengujian terhadap Pasal 43 ayat (1 UU Perkawinan (UU NO 1 Tahun 1974 jika dilihat dari sudut kepastian

  16. Underground Test Area Subproject Phase I Data Analysis Task. Volume VIII - Risk Assessment Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-12-01

    Volume VIII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the risk assessment documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  17. Comercio Internacional mediterráneo en el siglo VIII a.C.

    Directory of Open Access Journals (Sweden)

    Paloma Cabrera Bonet

    2018-01-01

    Full Text Available The VIII century B.C. saw, for the first time after the breakdown of the system in the Late Bronze Age, the revival of a true intemational trade at a growing scale, especíally protagonized by Phoenicians and Greeks. In this article we analyze sorne aspects of this phenomenon, from the Aegean to the Far West, which made possíble, through a vaste network of trading routes, a large multinational ínteractíon. We understand the international trade as a key factor in the proccess of economic, social and political changes of the Mediterranean areas submerged in this complex "world-system".

  18. Production of Lentiviral Vectors Encoding Recombinant Factor VIII Expression in Serum-Free Suspension Cultures

    Directory of Open Access Journals (Sweden)

    Angelo Luis Caron

    2015-12-01

    Full Text Available ABSTRACT Lentiviral vector-mediated gene transfer offers several advantages over other gene delivery vectors when considering gene and cell therapy applications. However, using these therapies in clinical applications involves large-scale vector production in an efficient and cost-effective manner. Here we describe a high yield production of a lentivirus encoding recombinant factor VIII in a scalable and GMP-compliant culture system, based on serum free suspension cultures and transient transfection with an inexpensive reagent, polyethylenimine (PEI, reaching a total viral yield of 2.48x108 particles.

  19. Measurements of Sheath Currents and Equilibrium Potential on the Explorer VIII Satellite (1960 xi)

    Science.gov (United States)

    Bourdeau, R. E.; Donley, J. L.; Serbu, G. P.; Whipple, E. C., Jr.

    1961-01-01

    Experimental data were obtained from the Explorer VIII satellite on five parameters pertinent to the problem of the interaction of space vehicles with an ionized atmosphere. The five parameters are: photoemission current due to electrons emitted from the satellite surfaces as a result of solar radiation; electron and positive ion currents due to the diffusion of charged particles from the medium to the spacecraft; the vehicle potential relative to the medium, and the ambient electron temperature. Included in the experimental data is the aspect dependence of the photoemission and diffusion currents. On the basis of the observations, certain characteristics of the satellite's plasma sheath are postulated.

  20. One-dimensional Arterial Network Model for Bypass Grafts Assessment

    CERN Document Server

    Ghigo, Arthur; Wang, Xiaofei; Lagrée, Pierre-Yves; Fullana, Jose-Maria

    2016-01-01

    We propose an arterial network model based on 1D blood hemodynamic equations to study the behavior of different vascular surgical bypass grafts in case of an arterial occlusive pathology: an obliteration or stenosis of the iliac artery. We investigate the performances of three different bypass grafts (Aorto-Femoral, Axillo-Femoral and cross-over Femoral) depending on the degree of obliteration of the stenosis. Numerical simulations show that all bypass grafts are efficient since we retrieve in all cases the normal hemodynamics in the stenosed region while ensuring at the same time a global healthy circulation. We analyze in particular the Axillo-Femoral bypass graft by performing hundreds of simulations by varying the values of the Young's modulus [0.1--50 MPa] and the radius [0.01--5 cm] of the bypass graft. We show that the Young's modulus and radius of commercial bypass grafts are optimal in terms of hemodynamic considerations. The numerical findings prove that this approach could be used to optimize or pl...

  1. Progress on Complications of Direct Bypass for Moyamoya Disease.

    Science.gov (United States)

    Yu, Jinlu; Shi, Lei; Guo, Yunbao; Xu, Baofeng; Xu, Kan

    2016-01-01

    Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD.

  2. Variations in dietary intake after bypass surgery for obesity. Possible relation to development of fatty liver after jejunoileal bypass

    Energy Technology Data Exchange (ETDEWEB)

    Rogus, J.; Blumenthal, S.A.

    1981-01-01

    Consumption of nutrients and food energy was compared, with concomitant chemical and radiologic measurements of hepatic fat content, preoperatively and postoperatively in 25 patients who underwent gastric or jejunoileal bypass for obesity. Patients in the two operative groups ingested similar quantities of food before surgery. After surgery, caloric intake from all sources decreased in both groups but to a significantly greater extent in the gastric bypass patients. During the first six months postoperatively, the 13 gastric bypass patients showed no changes in hepatic fat content, whereas substantial increases in liver fat uniformly occurred in the 12 patients who had jejunoileal bypasses. It is suggested that dietary carbohydrate may have contributed to the accretion of liver fat in these 12 patients.

  3. Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure.

    Science.gov (United States)

    Hossne Junior, Nelson Américo; Miranda, Matheus; Monteiro, Marcus Rodrigo; Branco, João Nelson Rodrigues; Vargas, Guilherme Flora; Pestana, José Osmar Medina de Abreu; Gomes, Walter José

    2015-01-01

    Coronary artery bypass grafting is currently the best treatment for dialysis patients with multivessel coronary artery involvement. Vasoplegic syndrome of inflammatory etiology constitutes an important postoperative complication, with highly negative impact on prognosis. Considering that these patients have an intrinsic inflammatory response exacerbation, our goal was to evaluate the incidence and mortality of vasoplegic syndrome after myocardial revascularization in this group. A retrospective, single-center study of 50 consecutive and non-selected dialysis patients who underwent myocardial revascularization in a tertiary university hospital, from 2007 to 2012. The patients were divided into 2 groups, according to the use of cardiopulmonary bypass or not (off-pump coronary artery bypass). The incidence and mortality of vasoplegic syndrome were analyzed. The subgroup of vasoplegic patients was studied separately. There were no preoperative demographic differences between the cardiopulmonary bypass (n=20) and off-pump coronary artery bypass (n=30) group. Intraoperative data showed a greater number of distal coronary arteries anastomosis (2.8 vs. 1.8, Pcardiopulmonary bypass group. Vasoplegia incidence was statistically higher (P=0.0124) in the cardiopulmonary bypass group (30%) compared to the off-pump coronary artery bypass group (3%). Vasoplegia mortality was 50% in the cardiopulmonary bypass group and 0% in the off-pump coronary artery bypass group. The vasoplegic subgroup analysis showed no statistically significant clinical differences. Cardiopulmonary bypass increased the risk for developing postoperative vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure.

  4. KEEFEKTIFAN MODEL TGT DENGAN PENDEKATAN SCIENTIFIC BERBANTUAN CD PEMBELAJARAN TERHADAP KEMAMPUAN PEMECAHAN MASALAH SISWA SMP KELAS VIII PADA MATERI LINGKARAN

    Directory of Open Access Journals (Sweden)

    Singgih Baswendro

    2015-11-01

    Full Text Available Artikel ini dibuat berdasarkan penelitian skripsi yang telah dilaksanakan. Tujuan penelitian ini adalah (1 untuk mengetahui hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 untuk mengetahui rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Penelitian ini dilaksanakan di SMP Negeri 3 Ungaran dengan populasi siswa kelas VIII tahun ajaran 2014/2015. Pengambilan kelas sampel menggunakan teknik cluster random sampling. Untuk mengetahui hasil penelitian ini, data hasil akhir diuji dengan uji proporsi dan uji perbedaan rata-rata. Hasil penelitan ini menunjukkan bahwa (1 hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Dengan ini maka model TGT dengan pendekatan scientific berbantuan CD pembelajaran efektif terhadap kemampuan pemecahan masalah siswa.

  5. Coronary artery bypass grafting in octogenarians.

    Science.gov (United States)

    Sakamoto, S; Matsubara, J; Matsubara, T; Nagayoshi, Y; Nishizawa, H; Shouno, S; Kouno, M; Takeuchi, K; Nonaka, T

    2001-10-01

    Preoperative profiles, postoperative complications, and the early and late results in 32 patients 80 yrs. of age and older (elderly group) who underwent coronary artery bypass grafting were compared with those in patients under 80 yrs. of age (control group). In the elderly group, the prevalence of patients with preoperative creatinine clearance (Ccr.) <50 l/day (34.4%), unstable angina pectoris (78.1%) and left main trunk disease (40.1%) was significantly higher than those in the control group. The incidences of arrhythmia and intensive care unit(ICU) syndrome were also significantly higher in the elderly group than in the control group, however, there was no death due to these complications. In the elderly group, one patient (3.1%) died in the hospital due to low cardiac output syndrome (LOS), while three patients (2.4%) of the control group died in the hospital. As for the long-term results, the 5-yr. survival rates for the elderly group and the control group were 82.6% and 85.2%, respectively, and the effectiveness of surgery was remarkable, with improved postoperative activity in 96.9% of the elderly group. These findings indicate that although the elderly patients have higher risks by undergoing surgery and have a disadvantage in the rate of postoperative complications, the postoperative improvement in activity and survival rate can be similar to those in the younger patients.

  6. Stabilizing family life after gastric bypass surgery.

    Science.gov (United States)

    Bylund, Ami; Benzein, Eva; Sandgren, Anna

    2017-12-01

    Weight-loss surgery requires lifelong lifestyle modifications for the maintenance of weight loss and health effects, and can affect both the individual and family. Earlier research indicates that the quality of social relationships has positive and negative influences on wellbeing and health. There is little research on family-life after a member has undergone gastric bypass (GBP) against obesity. Thus, this study aimed to develop a classic grounded theory about families with a member treated with GBP against obesity. The study design used classic grounded theory and included data from 16 interviews. Families' shared a main concern of unexpected changes after GBP, resulting in the theory Stabilizing family life, explained as a social process to decrease uncertainty and find stability and well-being in family interactions. The social process develops differently which entail families: attaining unity, returning to old patterns, or disconnecting to find stability, depending on the discrepancy in expectations and knowledge. This is affected by the overall life situation, life-stage and relationship quality. The theory highlights unexpected change as a potential challenge for the family, as well as how they resolve this. Hence, the theory can be applied in care strategies for families. Identification of families needing support to stabilize family life after GBP requires further research.

  7. Cardiopulmonary bypass and edema: physiology and pathophysiology.

    Science.gov (United States)

    Hirleman, E; Larson, D F

    2008-11-01

    Edema is a common morbidity following cardiopulmonary bypass (CPB) and can result in injury to many organs, including the heart, lungs, and brain. Generalized edema is also common and can lead to increased post-operative hospital stay and other morbidities. Pediatric patients are more susceptible to post-CPB edema and the consequences are more severe for this population. Hemodilution and systemic inflammatory responses are two suspected causes of CPB-related edema; however, the mechanisms involved are far from understood. Also, the common strategies to improve edema have not been completely successful and there is a need for new strategies at maintaining a fluid balance of patients as close to physiological as possible, especially for pediatric patients. An integrative approach to understanding edema is necessary as the forces involved in fluid homeostasis are dynamic and interdependent. Therefore, this review will focus on the physiology of fluid homeostasis and the pathologies of fluid shifts during CPB which lead to general edema as well as tissue-specific edema.

  8. AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Yurong; Guo, Yan; Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, The Fourth Military Medical University, Shaanxi, Xi' an (China); Zhang, Jian; Li, Xia; Shen, Lan; Ru, Yi [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Shaanxi, Xi' an (China); Xue, Yan [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, The Fourth Military Medical University, Shaanxi, Xi' an (China); Zheng, Jin [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, The Fourth Military Medical University, Shaanxi, Xi' an (China); Liu, Xinping; Zhang, Jing; Yao, Libo [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Shaanxi, Xi' an (China)

    2013-04-05

    Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h) compared to 5.1% in control cells (P < 0.05). Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia group vs control group) at 3 h in MKN28 cells, respectively (P < 0.05). We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM) decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4%) treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8%) of cells treated with hyperthermia alone (P < 0.05). Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.

  9. AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Yurong Tao

    2013-05-01

    Full Text Available Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2, a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h compared to 5.1% in control cells (P < 0.05. Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia group vs control group at 3 h in MKN28 cells, respectively (P < 0.05. We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4% treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8% of cells treated with hyperthermia alone (P < 0.05. Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.

  10. AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Yurong Tao

    2013-04-01

    Full Text Available Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2, a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h compared to 5.1% in control cells (P < 0.05. Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia group vs control group at 3 h in MKN28 cells, respectively (P < 0.05. We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4% treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8% of cells treated with hyperthermia alone (P < 0.05. Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.

  11. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  12. Alpha glucosidase inhibitors

    National Research Council Canada - National Science Library

    Kalra, Sanjay

    2014-01-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action...

  13. Proton pump inhibitors

    Science.gov (United States)

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by glands in ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

  14. Indonesian Interference on English Language in VIII Grade Junior High School Students

    Directory of Open Access Journals (Sweden)

    Agustia Km Tri Sutrisna

    2018-01-01

    Full Text Available This study aims to determine the type of Indonesian interference found in English language among class VIII SMPK 2 Harapan Untal-Untal students. This research is done by analyzing the result of simple text translation done by the students of class VIII SMPK 2 Harapan Untal-Untal, then from the translation result will be analyzed what kind of interference that appeared. Methods of data collection in this study using observational research methods and literature. The data that have been collected in the form of simple translations from the students will be analyzed descriptively using related theories to find out what kind of interference found in the analysis. Further, in relating to interference, it will find a way out to reduce and even eliminate Indonesian interference itself. The results to be achieved in this research is recognize the level of Indonesian language interference in the use of English among the junior high school students, then find the practical efforts to be done so that interference does not increased. So, the use and English understanding can be done as much as possible. The finding of the paper found that 6 interference such as grammar structure, subject pronoun, adjectives, auxiliaries, preposition and word order.

  15. PENGEMBANGAN PERANGKAT AJAR MODEL CORE PENDEKATAN METAKOGNITIF UNTUK MENINGKATKAN KEMAMPUAN PEMECAHAN MASALAH GEOMETRI KELAS VIII

    Directory of Open Access Journals (Sweden)

    Daroinis Sa’adah

    2017-02-01

    Full Text Available The objectives of this study are to develop teaching aids, to test the validity and practically teaching aids, and to test the effectiveness of learning process using CORE (Connecting, Organizing, Reflecting, and Extending model with metacognitive approach to improve the ability in Geometri problem solving. This research and development design is adapted from Plomp model by using several phases: (1 preliminary investigation; (2 design; (3 realization/construction; (4 test, evaluation and revision. This study developed some teaching aids; a part of syllabus, lesson plan, students book, students’ work sheet, and test of problem solving ability. The subject of the try out is eighth graders of MTs NU Nurul Huda Kudus. The research data to test the validity, practically, and effectiveness are collected by: (1 validation sheet; (2 observation sheet; (3 problem solving test. The results of research showed that development teaching aids using CORE model with metacognitive approach for Geometry material of VIII grade is valid and practical, and learning CORE model with metacognitive approach for Geometry material of VIII grade is effective.

  16. The head that wears the crown: Henry VIII and traumatic brain injury.

    Science.gov (United States)

    Ikram, Muhammad Qaiser; Sajjad, Fazle Hakim; Salardini, Arash

    2016-06-01

    Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Detection of Fibrinogen and Coagulation Factor VIII in Plasma by a Quartz Crystal Microbalance Biosensor

    Directory of Open Access Journals (Sweden)

    Chunyan Yao

    2013-05-01

    Full Text Available A quartz crystal microbalance (QCM biosensor with nanogram sensitivity has been constructed through a reasonable designing and biological processing of the piezoelectric quartz crystals. Due to its highly sensitivity, real time detection and low cost, the proposed QCM biosensor has a promising potential in blood coagulation research. In the current study, the QCM biosensor was used to determine the activated partial thromboplastin time (APTT for 120 anticoagulated plasma specimens. A good linear relationship was found in a double-logarithmic plot of APTT versus fibrinogen concentration in the range of 1.58–6.30 g/L. For factor VIII, the detection range by the QCM biosensor is 0.0185–0.111 mg/L. The QCM biosensor results were compared with those obtained by commercial optical coagulometry and a good agreement (correlation coefficient is 0.949 for fibrinogen, and 0.948 for factor VIII was reached. Furthermore, the QCM determination can be completed within 10 min. Our study suggested that the proposed QCM biosensor could provide for more convenient and time saving operations, which may be useful in clinical situations for rapid monitoring of anticoagulant therapy using small volume (20 μL plasma specimens.

  18. Improving attitudes toward mathematics learning with problem posing in class VIII

    Science.gov (United States)

    Vionita, Alfha; Purboningsih, Dyah

    2017-08-01

    This research is classroom action research which is collaborated to improve student's behavior toward math and mathematics learning at class VIII by using problem posing approach. The subject of research is all of students grade VIIIA which consist of 32 students. This research has been held on two period, first period is about 3 times meeting, and second period is about 4 times meeting. The instrument of this research is implementation of learning observation's guidance by using problem posing approach. Cycle test has been used to measure cognitive competence, and questionnaire to measure the students' behavior in mathematics learning process. The result of research shows the students' behavior has been improving after using problem posing approach. It is showed by the behavior's criteria of students that has increasing result from the average in first period to high in second period. Furthermore, the percentage of test result is also improve from 68,75% in first period to 78,13% in second period. On the other hand, the implementation of learning observation by using problem posing approach has also improving and it is showed by the average percentage of teacher's achievement in first period is 89,2% and student's achievement 85,8%. These results get increase in second period for both teacher and students' achievement which are 94,4% and 91,11%. As a result, students' behavior toward math learning process in class VIII has been improving by using problem posing approach.

  19. KEANEKARAGAMAN HYMENOPTERA PARASITOID PADA PERKEBUNAN KELAPA SAWIT PTPN VIII CINDALI, BOGOR

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    Ichsan Luqmana Indra Putra

    2016-09-01

    Full Text Available Diversity of parasitic Hymenoptera in PTPN VIII oil palm plantation Cindali, Bogor. One group of important natural enemies in oil palm plantation is parasitic Hymenoptera. The purpose of this research is to know the diversity and fluctuation of parasitic Hymenoptera PTPN VIII Cindali oil palm plantation. This research was conducted in 6 blocks of oil palm in September 2014 – June 2015. There were 5 plots in every observation blocks 39.2 x 39.2 m in size, and used direct and indirect method. Direct method done by 5 plants in every plots was taken randomized to observed and taken the herbivore insects to reared until the parasitic Hymenoptera came out. Observation of cover crops conducted by 3 subplots determined diagonally in every plots 9.8 x 9.8 m in size and herbivore insects was observed and collected. Indirect methods used sweep net and yellow pan trap. The result of this research, 26 parasitic Hymenoptera families was found, with the Braconidae was the most morphospecies found and the most individual amount was Scelionidae. The abundance of parasitoid in every month fluctuated.

  20. PENGARUH KONSELING KELOMPOK TERHADAP KONFORMITAS SISWI KELAS VIII SMPIT BINA AMAL SEMARANG

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    sudyastuti sudyastuti

    2017-03-01

    Full Text Available This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the psychology scale. Data analysis techniques using deskriptif analysis of percentage and wilcoxon test. The results showed incoming students conformity category is middle (59,75%. After being given the treatment through the counseling of the group, a significant unchanged in conformity of students. Conformity of the students in a middle category (60,37%. It shows that conformity of student can’t be influenced through the counseling service groups. Conformity of students not depend on one cause but the another thing to establish it as cohesion,the pretension to change, and the environmental support.

  1. PROSES BERPIKIR SISWA KELAS VIII DALAM MENYELESAIKAN SOAL MATEMATIKA TIMSS MATERI BESAR SUDUT DALAM BENTUK GEOMETRIS

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    Nurul Hidayati Arifani

    2017-07-01

    Full Text Available This study aims to describe the students' thinking process in solving TIMSS math problem on measurement of angle in geometric shapes based on Polya’s problem solving step associated with Swartz’s thinking process theory. The subject of the research was a grade VIII student in SMP Negeri 4 Malang who was classified as intelligent but made many mistakes when completing the test. Data collection methods used were test and interview methods. The results show that students go through the step of generating ideas, clarifying ideas, assessing the reasonableness of ideas, and thinking complex on every step of problem solving, but at the look back step, students do not clarify the idea. Penelitian ini bertujuan untuk mendeskripsikan proses berpikir siswa dalam menyelesaikan soal matematika TIMSS materi besar sudut dalam bentuk geometris berdasarkan langkah penyelesaian masalah Polya yang dikaitkan dengan teori proses berpikir Swartz. Subjek penelitian adalah seorang siswa kelas VIII di SMP Negeri 4 Malang yang tergolong pandai, tetapi banyak melakukan kesalahan saat menyelesaikan soal tes. Metode pengumpulan data yang digunakan adalah metode tes dan wawancara. Hasil penelitian menunjukkan bahwa siswa dalam menyelesaikan soal TIMSS melalui tahap menghasilkan ide, mengklarifikasi ide, menilai kelayakan ide, dan berpikir kompleks pada setiap langkah penyelesaian masalah. Namun, pada tahap memeriksa kembali, siswa tidak melakukan pengklarifikasian ide.

  2. Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels.

    Science.gov (United States)

    Alami, Meriem; Vacher, Hélène; Bosmans, Frank; Devaux, Christiane; Rosso, Jean-Pierre; Bougis, Pierre E; Tytgat, Jan; Darbon, Hervé; Martin-Eauclaire, Marie-France

    2003-11-01

    The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion alpha-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v)1.2 or rat skeletal muscle Na+ channel rNa(v)1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29+/-5 and 416+/-14 nM respectively for AmmVIII and 2.6+/-0.3 nM and 2.2+/-0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the X-ray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.

  3. Evaluation of B&W UO2/ThO2 VIII experimental core: criticality and thermal disadvantage factor analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carlo Parisi; Emanuele Negrenti

    2017-02-01

    In the framework of the OECD/NEA International Reactor Physics Experiment (IRPHE) Project, an evaluation of core VIII of the Babcock & Wilcox (B&W) Spectral Shift Control Reactor (SSCR) critical experiment program was performed. The SSCR concept, moderated and cooled by a variable mixture of heavy and light water, envisaged changing of the thermal neutron spectrum during the operation to encourage breeding and to sustain the core criticality. Core VIII contained 2188 fuel rods with 93% enriched UO2-ThO2 fuel in a moderator mixture of heavy and light water. The criticality experiment and measurements of the thermal disadvantage factor were evaluated.

  4. Bypass surgery for complex middle cerebral artery aneurysms: an algorithmic approach to revascularization.

    Science.gov (United States)

    Tayebi Meybodi, Ali; Huang, Wendy; Benet, Arnau; Kola, Olivia; Lawton, Michael T

    2017-09-01

    OBJECT Management of complex aneurysms of the middle cerebral artery (MCA) can be challenging. Lesions not amenable to endovascular techniques or direct clipping might require a bypass procedure with aneurysm obliteration. Various bypass techniques are available, but an algorithmic approach to classifying these lesions and determining the optimal bypass strategy has not been developed. The objective of this study was to propose a comprehensive and flexible algorithm based on MCA aneurysm location for selecting the best of multiple bypass options. METHODS Aneurysms of the MCA that required bypass as part of treatment were identified from a large prospectively maintained database of vascular neurosurgeries. According to its location relative to the bifurcation, each aneurysm was classified as a prebifurcation, bifurcation, or postbifurcation aneurysm. RESULTS Between 1998 and 2015, 30 patients were treated for 30 complex MCA aneurysms in 8 (27%) prebifurcation, 5 (17%) bifurcation, and 17 (56%) postbifurcation locations. Bypasses included 8 superficial temporal artery-MCA bypasses, 4 high-flow extracranial-to-intracranial (EC-IC) bypasses, 13 IC-IC bypasses (6 reanastomoses, 3 reimplantations, 3 interpositional grafts, and 1 in situ bypass), and 5 combination bypasses. The bypass strategy for prebifurcation aneurysms was determined by the involvement of lenticulostriate arteries, whereas the bypass strategy for bifurcation aneurysms was determined by rupture status. The location of the MCA aneurysm in the candelabra (Sylvian, insular, or opercular) determined the bypass strategy for postbifurcation aneurysms. No deaths that resulted from surgery were found, bypass patency was 90%, and the condition of 90% of the patients was improved or unchanged at the most recent follow-up. CONCLUSIONS The bypass strategy used for an MCA aneurysm depends on the aneurysm location, lenticulostriate anatomy, and rupture status. A uniform bypass strategy for all MCA aneurysms does not

  5. Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

    Science.gov (United States)

    Kouides, Peter; Wawra-Hehenberger, Kathrin; Sajan, Anna; Mead, Henry; Simon, Toby

    2017-10-01

    Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. More than 33 years of pharmacovigilance data continue to support the safety of Humate-P. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  6. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Tiede, Andreas; Hofbauer, Christoph J; Werwitzke, Sonja; Knöbl, Paul; Gottstein, Saskia; Scharf, Rüdiger E; Heinz, Jürgen; Groß, Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, Fritz; Koch, Armin; Reipert, Birgit M

    2016-05-12

    Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA. © 2016 by The American Society of Hematology.

  7. New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A.

    Science.gov (United States)

    de Alencar, J B; Macedo, L C; de Barros, M F; Rodrigues, C; Shinzato, A H; Pelissari, C B; Machado, J; Sell, A M; Visentainer, J E L

    2015-07-01

    The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5-7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro-coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form. We investigated the polymorphisms in regulatory regions of cytokine genes (IL1A, IL1B, IL1R, IL1RA, IL4RA, IL12, INFG, TGFB1, TNF, IL2, IL4, IL6, IL10) that could influence the risk of developing inhibitors in patients with severe HA. The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines(®) , Canoga Park, USA) RESULTS: From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in INFG and of +869 TT and TG/TG in TGFB1 genes on patients with inhibitors. This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII. © 2015 John Wiley & Sons Ltd.

  8. Annular MHD Physics for Turbojet Energy Bypass

    Science.gov (United States)

    Schneider, Steven J.

    2011-01-01

    The use of annular Hall type MHD generator/accelerator ducts for turbojet energy bypass is evaluated assuming weakly ionized flows obtained from pulsed nanosecond discharges. The equations for a 1-D, axisymmetric MHD generator/accelerator are derived and numerically integrated to determine the generator/accelerator performance characteristics. The concept offers a shockless means of interacting with high speed inlet flows and potentially offers variable inlet geometry performance without the complexity of moving parts simply by varying the generator loading parameter. The cycle analysis conducted iteratively with a spike inlet and turbojet flying at M = 7 at 30 km altitude is estimated to have a positive thrust per unit mass flow of 185 N-s/kg. The turbojet allowable combustor temperature is set at an aggressive 2200 deg K. The annular MHD Hall generator/accelerator is L = 3 m in length with a B(sub r) = 5 Tesla magnetic field and a conductivity of sigma = 5 mho/m for the generator and sigma= 1.0 mho/m for the accelerator. The calculated isentropic efficiency for the generator is eta(sub sg) = 84 percent at an enthalpy extraction ratio, eta(sub Ng) = 0.63. The calculated isentropic efficiency for the accelerator is eta(sub sa) = 81 percent at an enthalpy addition ratio, eta(sub Na) = 0.62. An assessment of the ionization fraction necessary to achieve a conductivity of sigma = 1.0 mho/m is n(sub e)/n = 1.90 X 10(exp -6), and for sigma = 5.0 mho/m is n(sub e)/n = 9.52 X 10(exp -6).

  9. Tricarboxylic Acid Cycle and Glyoxylate Bypass.

    Science.gov (United States)

    Cronan, John E; Laporte, David

    2005-11-01

    The tricarboxylic acid (TCA) cycle plays two essential roles in metabolism. First, under aerobic conditions the cycle is responsible for the total oxidation of acetyl-CoA that is derived mainly from the pyruvate produced by glycolysis. Second, TCA cycle intermediates are required in the biosynthesis of several amino acids. Although the TCA cycle has long been considered a "housekeeping" pathway in Escherichia coli and Salmonella enterica, the pathway is highly regulated at the transcriptional level. Much of this control is exerted in response to respiratory conditions. The TCA cycle gene-protein relationship and mutant phenotypes have been well studied, although a few loose ends remain. The realization that a "shadow" TCA cycle exists that proceeds through methylcitrate has cleared up prior ambiguities. The glyoxylate bypass has long been known to be essential for growth on carbon sources such as acetate or fatty acids because this pathway allowsnet conversion of acetyl-CoA to metabolic intermediates. Strains lacking this pathway fail to grow on these carbon sources, since acetate carbon entering the TCA cycle is quantitatively lost as CO2 resulting in the lack of a means to replenish the dicarboxylic acids consumed in amino acid biosynthesis. The TCA cycle gene-protein relationship and mutant phenotypes have been well studied, although the identity of the small molecule ligand that modulates transcriptional control of the glyoxylate cycle genes by binding to the IclR repressor remains unknown. The activity of the cycle is also exerted at the enzyme level by the reversible phosphorylation of the TCA cycle enzyme isocitrate dehydrogenase catalyzed by a specific kinase/phosphatase to allow isocitratelyase to compete for isocitrate and cleave this intermediate to glyoxylate and succinate.

  10. Inhibitor development in nonsevere hemophilia A

    NARCIS (Netherlands)

    Eckhardt, C.L.

    2014-01-01

    Hemophilia A is an X-linked inherited bleeding disorder that affects approximately 1 in 5000 male live births. It is caused by a deficient plasma level of clotting factor VIII and can be treated by the intravenous administration of factor VIII concentrates. A severe complication of the treatment

  11. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    Science.gov (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Diagnostic and prognostic value of factor VIII binding antibodies in acquired hemophilia A: data from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Werwitzke, S; Geisen, U; Nowak-Göttl, U; Eichler, H; Stephan, B; Scholz, U; Holstein, K; Klamroth, R; Knöbl, P; Huth-Kühne, A; Bomke, B; Tiede, A

    2016-05-01

    Essentials Factor VIII (FVIII) binding IgG detected by ELISA could be an alternative to the Bethesda assay. We studied the performance of anti-FVIII IgG ELISA in patients with acquired hemophilia and controls. Anti-FVIII IgG > 99th percentile of controls was highly sensitive and specific. Patients with high anti-FVIII IgG have a lower chance of achieving remission. Background Acquired hemophilia A is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay is the diagnostic reference standard for detecting neutralizing autoantibodies against factor VIII (FVIII), but is not widely available, not ideal for quantifying the complex type 2 inhibitors seen in acquired hemophilia, and suffers from high inter-laboratory variability. Objectives To assess the diagnostic and prognostic value of FVIII-binding antibodies as detected by ELISA compared with the Nijmegen Bethesda assay. Methods Samples from the time of first diagnosis and clinical data were available from 102 patients with acquired hemophilia enrolled in the prospective GTH-AH 01/2010 study. Controls (n = 102) were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve analysis. The prognostic value was assessed in 92 of the 102 patients by Cox regression analysis of time to partial remission. Results Anti-FVIII IgG above the 99th percentile (> 15 arbitrary units per mL) revealed high sensitivity and specificity (both 0.99; 95% confidence interval, 0.95-1.0) for diagnosing acquired hemophilia. The likelihood of achieving partial remission was related to anti-FVIII IgG concentration ( 1050, 0.39). The Bethesda titer was only associated with the likelihood of partial remission when analyzed in the central laboratory, but not when data from local GTH study sites were used. Conclusion Although the Nijmegen-modified Bethesda assay is the reference

  13. An Experimental Design of Bypass Magneto-Rheological (MR) damper

    Science.gov (United States)

    Rashid, MM; Aziz, Mohammad Abdul; Raisuddin Khan, Md.

    2017-11-01

    The magnetorheological (MR) fluid bypass damper fluid flow through a bypass by utilizing an external channel which allows the controllability of MR fluid in the channel. The Bypass MR damper (BMRD) contains a rectangular bypass flow channel, current controlled movable piston shaft arrangement and MR fluid. The static piston coil case is winding by a coil which is used inside the piston head arrangement. The current controlled coil case provides a magnetic flux through the BMRD cylinder for controllability. The high strength of alloy steel materials are used for making piston shaft which allows magnetic flux propagation throughout the BMRD cylinder. Using the above design materials, a Bypass MR damper is designed and tested. An excitation of current is applied during the experiment which characterizes the BMRD controllability. It is shown that the BMRD with external flow channel allows a high controllable damping force using an excitation current. The experimental result of damping force-displacement characteristics with current excitation and without current excitation are compared in this research. The BMRD model is validated by the experimental result at various frequencies and applied excitation current.

  14. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    Directory of Open Access Journals (Sweden)

    Scott B Vafai

    Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

  15. Thermal activation of dislocations in large scale obstacle bypass

    Science.gov (United States)

    Sobie, Cameron; Capolungo, Laurent; McDowell, David L.; Martinez, Enrique

    2017-08-01

    Dislocation dynamics simulations have been used extensively to predict hardening caused by dislocation-obstacle interactions, including irradiation defect hardening in the athermal case. Incorporating the role of thermal energy on these interactions is possible with a framework provided by harmonic transition state theory (HTST) enabling direct access to thermally activated reaction rates using the Arrhenius equation, including rates of dislocation-obstacle bypass processes. Moving beyond unit dislocation-defect reactions to a representative environment containing a large number of defects requires coarse-graining the activation energy barriers of a population of obstacles into an effective energy barrier that accurately represents the large scale collective process. The work presented here investigates the relationship between unit dislocation-defect bypass processes and the distribution of activation energy barriers calculated for ensemble bypass processes. A significant difference between these cases is observed, which is attributed to the inherent cooperative nature of dislocation bypass processes. In addition to the dislocation-defect interaction, the morphology of the dislocation segments pinned to the defects play an important role on the activation energies for bypass. A phenomenological model for activation energy stress dependence is shown to describe well the effect of a distribution of activation energies, and a probabilistic activation energy model incorporating the stress distribution in a material is presented.

  16. Photovoltaic-module bypass-diode encapsulation. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    1983-06-20

    The design and processing techniques necessary to incorporate bypass diodes within the module encapsulant are presented in this annual report. A comprehensive survey of available pad-mounted PN junction and Schottky diodes led to the selection of Semicon PN junction diode cells for this application. Diode junction-to-heat spreader thermal resistance measurements, performed on a variety of mounted diode chip types and sizes, have yielded values which are consistently below 1/sup 0/C per watt, but show some instability when thermally cycled over the temperature range from -40 to 150/sup 0/C. Based on the results of a detailed thermal analysis, which covered the range of bypass currents from 2 to 20 amperes, three representative experimental modules, each incorporating integral bypass diode/heat spreader assemblies of various sizes, were designed and fabricated. Thermal testing of these modules has enabled the formation of a recommended heat spreader plate sizing relationship. The production cost of three encapsulated bypass diode/heat spreader assemblies were compared with similarly rated externally-mounted packaged diodes. An assessment of bypass diode reliability, which relies heavily on rectifying diode failure rate data, leads to the general conclusion that, when proper designed and installed, these devices will improve the overall reliability of a terrestrial array over a 20 year design lifetime.

  17. Atrial Fibrillation, Neurocognitive Decline and Gene Expression After Cardiopulmonary Bypass.

    Science.gov (United States)

    Dalal, Rahul S; Sabe, Ashraf A; Elmadhun, Nassrene Y; Ramlawi, Basel; Sellke, Frank W

    2015-01-01

    Atrial fibrillation and neurocognitive decline are common complications after cardiopulmonary bypass. By utilizing genomic microarrays we investigate whether gene expression is associated with postoperative atrial fibrillation and neurocognitive decline. Twenty one cardiac surgery patients were prospectively matched and underwent neurocognitive assessments pre-operatively and four days postoperatively. The whole blood collected in the pre-cardiopulmonary bypass, 6 hours after-cardiopulmonary bypass, and on the 4th postoperative day was hybridized to Affymetrix Gene Chip U133 Plus 2.0 Microarrays. Gene expression in patients who developed postoperative atrial fibrillation and neurocognitive decline (n=6; POAF+NCD) was compared with gene expression in patients with postoperative atrial fibrillation and normal cognitive function (n=5; POAF+NORM) and patients with sinus rhythm and normal cognitive function (n=10; SR+NORM). Regulated genes were identified using JMP Genomics 4.0 with a false discovery rate of 0.05 and fold change of >1.5 or cardiopulmonary bypass, and 34 named genes four days postoperatively (Pcardiopulmonary bypass may have differential genomic responses compared to normal patients and patients with only postoperative atrial fibrillation, suggesting common pathophysiology for these conditions. Further exploration of these genes may provide insight into the etiology and improvements of these morbid outcomes.

  18. Are laparoscopic gastric bypass after gastroplasty and primary laparoscopic gastric bypass similar in terms of results?

    Science.gov (United States)

    Cadière, Guy-Bernard; Himpens, Jacques; Bazi, Michel; Cadière, Benjamin; Vouche, Michael; Capelluto, Elie; Dapri, Giovanni

    2011-06-01

    This retrospective study compares the results of primary gastric bypass (PGB) versus secondary gastric bypass (SGB) performed after gastroplasty. Between January 2004 and August 2008, 576 consecutive patients benefited from laparoscopic gastric bypass (LGB) in our hospital. Four hundred seventy patients (81.6%) were available for full evaluation. Primary outcome measures were operative time, conversion to open surgery and mortality, hospital stay, early and late complications, reoperations, efficacy, and patient satisfaction. Three hundred sixty-two patients benefited from a PGB and 108 from SGB. Median preoperative BMI was 42 kg/m2 (34.8-63.5; PGB) and 39 kg/m2 (20.9-64.5; SGB; p = 0.002). Median operative time was 109 min (40-436; PGB) and 194 min (80-430; SGB; p < 0.001). There was no conversion to open surgery or mortality in either group. Median hospital stay was 4 days (3-95; PGB) and 5 days (2-114; SGB; p < 0.001). Early complications were recorded in 37 patients (10.2%) after PGB and in 24 patients (22.2%) after SGB (p < 0.001). Reoperation was necessary in 12 patients (3.3%) after PGB and in 9 patients (8.3%) after SGB (p = 0.03). Median follow-up was 35 months (12-66; PGB), and 34 months (12-66; SGB; NS). Late complications were achieved in 46 patients (12.7%) after PGB and in 33 patients (30.6%) after SGB (p < 0.001). Reoperation was necessary in 17 patients (4.7%) after PGB and in 11 patients (10.2%) after SGB (p = 0.03). Mean % EWL was 74.2% after PGB and 69.9% after SGB (NS). After PGB, 89% of the patients was satisfied, 4% neutral, and 6% unsatisfied; after SGB, 79% was satisfied, 10% neutral, and 11% unsatisfied (p = 001). Weight loss after PGB and SGB is not statistically significantly different. Otherwise, operative time, hospital stay, complications, and revision rate are statistically significantly higher after SGB (p < 0.001).

  19. Keefektifan Experiential Learning Berbantuan Origami Terhadap Kemampuan Keruangan Siswa Kelas VIII

    Directory of Open Access Journals (Sweden)

    Isnaeni Umi Machromah

    2014-11-01

    Full Text Available AbstrakPenelitian eksperimen ini bertujuan untuk mengetahui keefektifan pembelajaran Experiential Learning berbantuan origami terhadap kemampuan keruangan siswa dengan kualifikasi keefektifan yang telah ditentukan. Populasi yaitu siswa kelas VIII SMP Negeri 3 Colomadu tahun pelajaran 2012/2013. Sampel diambil secara simple random sampling. Hasil penelitian ini yaitu: (1 Uji proporsi ketuntasan belajar menunjukkan siswa kelompok eksperimen telah mencapai ketuntasan belajar; (2 Uji perbedaan dua rata-rata menghasilkan simpulan bahwa rata-rata hasil post-test kemam-puan keruangan siswa kelompok eksperimen lebih dari kelompok kontrol; (3 Analisis re-gresi menunjukkan bahwa motivasi belajar siswa memberikan pengaruh positif sebesar 49,3% terhadap kemampuan keruangan siswa; (4 Uji gain ternormalisasi menunjukkan terdapat peningkatan kemampuan keruangan siswa secara signifikan pada kategaori sedang untuk kelompok eksperimen dan kategori rendah untuk kelompok kontrol. Simpulan yang diperoleh yaitu Experiential Learning berbantuan origami efektif terhadap kemampuan keruangan siswa kelas VIII. AbstractThis experiment research aims to determine the effectiveness of Experiential Learning with Origami to the students’s spatial abilities by the criteria of effectiveness. The population of this research is students of grade VIII of SMP Negeri 3 Colomadu 2012/2013 academic year. Independent variables used in this research are learning by Experiential Learning with origami and student’s motivation. While the dependent variable is the student’s spatial abilities. This research is using documentation, spatial abilities’s test, dan motivation’s scale for collecting data method. Result of this research are: (1 proportion test show that the experiment group has reached mastering of learning clasically and personally; (2 result of spatial ablities’s post test in experiment group better than control group; (3 result of regretion shows that student

  20. Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: studies of spatial dynamics of fibrin clot formation in hemophilia A.

    Science.gov (United States)

    Parunov, Leonid A; Soshitova, Natalia P; Fadeeva, Olga A; Balandina, Anna N; Kopylov, Konstantin G; Kumskova, Maria A; Gilbert, James C; Schaub, Robert G; McGinness, Kathleen E; Ataullakhanov, Fazoil I; Panteleev, Mikhail A

    2014-01-01

    In recent years, a number of tissue factor pathway inhibitor (TFPI) antagonists have been developed to serve as bypassing agents to improve hemostasis in hemophilia A. Since TFPI antagonists and FVIII concentrates are procoagulants, their combined effect on spatial clot formation could be potentially pro-thrombotic. To investigate the cooperative effect of TFPI inhibition and supplementation of FVIII in hemophilia A in a spatial, reaction-diffusion experiment in vitro. Plasma was collected at different time points from hemophilia A patients undergoing prophylaxis and was supplemented in vitro with TFPI inhibitor BAX499 (formerly ARC19499) at concentrations from 0 up to 600nM. Clotting propagation in recalcified plasma activated by a surface with immobilized tissue factor (TF) was monitored by videomicroscopy. Increasing concentration of BAX499 improved coagulation for all hemophilia A plasma samples activated with TF at 1.6pmole/m(2) by shortening lag time and increasing initial clot growth velocity and clot size. In contrast, plasma concentration of FVIII had little effect on lag time, but increased spatial clot growth velocity. There was a decrease in the BAX499 efficiency as FVIII concentration increased (lag time shortened by 50% if FVIII:C30%). The results indicate that BAX499 has an effect on clotting in hemophilia A plasma at low FVIII concentrations, however has little effect at high FVIII concentrations. © 2013.

  1. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Voorberg, Jan; Mertens, Koen

    2011-01-01

    Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both

  2. Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bierings, R.; Storm, G.; Voorberg, J.; Mertens, K.

    2007-01-01

    von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this

  3. Effectiveness of Peer Tutoring in Learning English among Tutors and Tutees of Class VIII Students in Kancheepuram DT

    Science.gov (United States)

    Marieswari, M.; Prema, N.

    2016-01-01

    The peer who teaches to their mates is peer tutoring. It is a common instructional strategy used in classrooms. The aim of this study is to know whether there is any improvement in achievement marks of tutors and tutees after the process of peer tutoring. Class VIII students were selected as the sample for the present experimental study. The…

  4. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  5. Mediastinal, subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient.

    Science.gov (United States)

    Omura, Yuka; Kusama, Yoshiki; Takeuchi, Noriko; Ishiwada, Naruhiko

    2018-01-17

    We report a case of mediastinal subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient. The patient arrived at the hospital with the chief complaint of immobility, and blood examination results suggested an acute infection and poorly controlled diabetes mellitus. Group B streptococcal bacteria were cultured from the patient's blood, and identified as serotype VIII upon further analysis. The patient recovered without any sequelae after percutaneous drainage, antibiotic therapy, and intensive glycemic control. Although the incidence of group B streptococcal infection in non-pregnant adults has recently increased in many developed countries, information on serotype VIII infection is quite limited. The reason is that serotype VIII group B streptococci are a Japan-specific serotype, and rarely cause invasive infections, even in Japan. Therefore, further surveillance and case reports should be documented in the future. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. 77 FR 42696 - Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2012-07-20

    ... Forest Service Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... Laws, Recreation Fee Coordinator, 406-283-7648 SUPPLEMENTARY INFORMATION: The Federal Recreation Lands... advance notice in the Federal Register whenever new recreation fee areas are established. This new fee...

  7. 78 FR 19445 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2013-04-01

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and maintenance of these recreation sites. Lake Canyon Recreation Area is a fee campground with 54... is to keep the site fees consistent with other campsites in the Lake Canyon Recreation Area. The fee...

  8. 75 FR 2850 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-01-19

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and recreation experiences. A financial analysis is being completed to determine fee rates. The.... Recreation Passes such as the Northwest Forest Pass would cover day use fees for this trailhead. Northwest...

  9. 76 FR 36518 - Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2011-06-22

    .... 2. An increase of fees for the Shelf Road Recreation Area in the Royal Gorge Field Office of the BLM..., Bureau of Land Management staff and Committee members. Persons who wish to bring recreation fee matters... Forest Service Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447...

  10. 75 FR 21583 - Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L...

    Science.gov (United States)

    2010-04-26

    ... Forest Service Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub... improve the recreation experience. An analysis of the campground shows that the proposed fees are..., Moab/Monticello Recreation Fee Coordinator, 435-636-3367. Information about proposed fee changes can...

  11. 78 FR 52499 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2013-08-23

    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: Monongahela National Forest, Forest Service, USDA. ACTION: Notice of new fee site... new recreation fee areas are established. This new fee will be reviewed by the Eastern Region...

  12. 78 FR 41783 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2013-07-11

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... comments can be compiled, analyzed and shared with a Recreation Resource Advisory Committee. New fees would... advance notice in the Federal Register whenever new recreation fee areas are established. Once public...

  13. 75 FR 80789 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2010-12-23

    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108... Agriculture to publish a six month advance notice in the Federal Register whenever new recreation fee areas are established. This new fee will be reviewed by the Colorado Recreation Resource Advisory Committee...

  14. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G

    2015-06-01

    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  15. 75 FR 5759 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-02-04

    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII... Recreation Fee Sites. SUMMARY: The Soda Springs Ranger District of the Caribou-Targhee National Forest is... appreciate and enjoy the availability of developed recreation campground and picnicking facilities. This...

  16. 75 FR 4340 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-01-27

    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII.... SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108-447) directed... new recreation fee areas are established. The Caribou-Targhee National Forest currently has nine other...

  17. 75 FR 26711 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-05-12

    ... No: 2010-11040] DEPARTMENT OF AGRICULTURE Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of New Recreation Fee Site. SUMMARY: Bethel Motorcycle and Bethel...

  18. 75 FR 26714 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII...

    Science.gov (United States)

    2010-05-12

    ... No: 2010-11042] DEPARTMENT OF AGRICULTURE Forest Service Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of Proposed New Recreation Fee Site. SUMMARY: Rattlesnake Bay...

  19. The potential of multi-compound nanoparticles to bypass drug resistance in cancer.

    Science.gov (United States)

    Da Silva, C G; Peters, Godefridus J; Ossendorp, Ferry; Cruz, Luis J

    2017-11-01

    The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. The PubMed literature was consulted and reviewed. Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

  20. Rankine cycle load limiting through use of a recuperator bypass

    Science.gov (United States)

    Ernst, Timothy C.

    2011-08-16

    A system for converting heat from an engine into work includes a boiler coupled to a heat source for transferring heat to a working fluid, a turbine that transforms the heat into work, a condenser that transforms the working fluid into liquid, a recuperator with one flow path that routes working fluid from the turbine to the condenser, and another flow path that routes liquid working fluid from the condenser to the boiler, the recuperator being configured to transfer heat to the liquid working fluid, and a bypass valve in parallel with the second flow path. The bypass valve is movable between a closed position, permitting flow through the second flow path and an opened position, under high engine load conditions, bypassing the second flow path.

  1. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy

    DEFF Research Database (Denmark)

    Patti, M E; McMahon, G; Mun, E C

    2005-01-01

    AIMS/HYPOTHESIS: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive...... was assessed in all three patients. RESULTS: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control...... of neuroglycopenia; pancreas pathology of all patients revealed diffuse islet hyperplasia and expansion of beta cell mass. CONCLUSIONS/INTERPRETATION: These findings suggest that gastric bypass-induced weight loss may unmask an underlying beta cell defect or contribute to pathological islet hyperplasia, perhaps via...

  2. Miller-Fisher syndrome after coronary artery bypass surgery.

    Science.gov (United States)

    Aldag, Mustafa; Albeyoglu, Sebnem; Ciloglu, Ufuk; Kutlu, Hakan; Ceylan, Levent

    2017-11-23

    Miller-Fisher syndrome (MFS) is an uncommon neurological disorder that is considered a variant of the Guillain-Barre syndrome (GBS). It is clinically defined by a triad of symptoms, namely ataxia, areflexia and ophthalmoplegia. These acute inflammatory polyradiculopathic syndromes can be triggered by viral infections, major surgery, pregnancy or vaccination. While the overall incidence of GBS is 1.2-2.3 per 100 000 per year, MFS is a relatively rare disorder. Only six cases of GBS after cardiac surgery have been reported, and to our knowledge, we describe the first case of MFS after coronary artery bypass surgery. Although cardiac surgery with cardiopulmonary bypass may increase the incidence of MFS and GBS, the pathological mechanism is unclear. Cardiac surgery may be a trigger for the immune-mediated response and may cause devastating complications. It is also important to be alert to de novo autoimmune and unexpected neurological disorders such as MFS after coronary bypass surgery.

  3. Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass

    Science.gov (United States)

    Salameh, Aida; Dhein, Stefan; Dähnert, Ingo; Klein, Norbert

    2016-01-01

    Aortocoronary bypass or valve surgery usually require cardiac arrest using cardioplegic solutions. Although, in principle, in a number of cases beating heart surgery (so-called off-pump technique) is possible, aortic or valve surgery or correction of congenital heart diseases mostly require cardiopulmonary arrest. During this condition, the heart-lung machine also named cardiopulmonary bypass (CPB) has to take over the circulation. It is noteworthy that the invention of a machine bypassing the heart and lungs enabled complex cardiac operations, but possible negative effects of the CPB on other organs, especially the brain, cannot be neglected. Thus, neuroprotection during CPB is still a matter of great interest. In this review, we will describe the impact of CPB on the brain and focus on pharmacological and non-pharmacological strategies to protect the brain. PMID:27879647

  4. Robotically assisted totally endoscopic coronary artery bypass surgery

    Science.gov (United States)

    Canale, Leonardo Secchin; Mick, Stephanie; Mihaljevic, Tomislav; Nair, Ravi

    2013-01-01

    Robotically assisted totally endoscopic coronary artery bypass surgery has emerged as a feasible and efficient alternative to conventional full sternotomy coronary artery bypass graft surgery in selected patients. This minimally invasive approach using the daVinci robotic system allows fine intrathoracic maneuvers and excellent view of the coronary arteries. Both on-pump and off-pump operations can be performed to treat single and multivessel disease. Hybrid approaches have the potential of offering complete revascularization with the “best of both worlds” from surgery (internal mammary artery anastomosis in less invasive fashion) and percutaneous coronary intervention (least invasive approach). In this article we review the indications, techniques, short and long term results, as well as current developments in totally endoscopic robotic coronary artery bypass operations. PMID:24251021

  5. Right ventricle contractility during early postoperative period after coronary artery bypass grafting with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    А. Е. Баутин

    2015-10-01

    Full Text Available Emphasis in this research was placed on contractility of the right ventricle with regard to its relationship with systemic hemodynamics in patients undergoing coronary artery bypass grafting (CABG under cardiopulmonary bypass (CPB. The study included 25 patients (14 males, 11 females, mean age was 587 years admitted to ICU after CABG under CPB. All patients required inotropic therapy. The criterion for prescribing inotropic support in the postoperative period was a drop of the stroke volume index of the left ventricle below 35 ml/m 2 provided that the values of this indicator were normal before the perfusion period. Patients with previous pathology of the right ventricle or right coronary artery were excluded from the study. To evaluate the right ventricular function and systemic hemodynamics indicators, use was made of the PiCCO plus system and VoLEF addon device. It was found out that reduced contractility of the right ventricle may cause the reduction in stroke volume of the left ventricle with normal contractility. It was also observed that the increase of preload in patients with right ventricular ejection fraction less than 30% does not improve its function but leads to the increase of its end-diastolic volume. In 68% of cases, the need in inotropic agents in the early postoperative period after CABG was associated with the drop in right ventricle contractility, in 40% - with isolated right ven-tricular dysfunction. Patients with isolated reduction in right ventricle contractility required a longer period of inotropic support and ICU stay as compared with those with left ventricular failure.

  6. Diabetes resolution after one anastomosis gastric bypass.

    Science.gov (United States)

    Abu-Abeid, Adam; Lessing, Yonatan; Pencovich, Niv; Dayan, Danit; Klausner, Joseph M; Abu-Abeid, Subhi

    2018-02-01

    Diabetes and other obesity-related diseases are a worldwide pandemic that transcends geographic borders as well as socioeconomic levels. Currently, it is well known that medical treatment alone is insufficient to ensure adequate and sustainable weight loss and co-morbidity resolution. It has been well proven that bariatric surgery can produce almost immediate resolution of diabetes and other co-morbidities as well as long-term weight loss. Here, we present our experience with the one anastomosis gastric bypass (OAGB) in terms of weight loss and diabetes resolution with 1 year of follow-up. Large, metropolitan, tertiary, university hospital. A retrospective analysis of all patients who underwent OAGB between March 2015 and March 2016 was performed. Patient demographic characteristics, co-morbidities, operative and postoperative data, as well as first year outcomes were collected and analyzed. There were 407 patients who underwent OAGB (254 females, average age 41.8 ± 12.05 yr, body mass index = 41.7 ± 5.77 kg/m 2 ). Of patients, 102 (25.1%) had diabetes with average glycosylated hemoglobin of 8.64 ± 1.94 g%, 93 (22.8%) had hypertension, 123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) had obstructive sleep apnea. The average length of hospital stay was 2.2 ± .84 days (range, 2-10 d). The average excess weight loss 1 year after surgery was 88.9 ± 27.3. After 1 year, follow-up data were available for more than 85% of the study's general population. Of 102 diabetic patients, only 8 (7.8%) were still considered diabetic and taking antidiabetic medication, with an average glycosylated hemoglobin of 5.4 ± 0.6. OAGB may be performed safely and with promising efficacy as both a primary and a revisional bariatric surgery, and it offers excellent resolution of diabetes. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  7. Acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Simpson, Scott A; Zaccagni, Hayden; Bichell, David P; Christian, Karla G; Mettler, Bret A; Donahue, Brian S; Roberts, L Jackson; Pretorius, Mias

    2014-07-01

    Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass. Single-center prospective randomized double-blinded study. University-affiliated pediatric hospital. Thirty children undergoing elective surgical correction of a congenital heart defect. Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass. Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury. Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free

  8. A Bypass Program of Supportive Instruction for Secondary Students with Learning Disabilities.

    Science.gov (United States)

    Mosby, Robert J.

    1979-01-01

    The developmental bypass teaching technique (which provides students an opportunity to bypass their learning deficits) was studied with regard to social studies achievement and classroom behaviors in 50 learning disabled junior high school students. (Author/PHR)

  9. Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response

    NARCIS (Netherlands)

    van den Goor, J.; Nieuwland, R.; van den Brink, A.; van Oeveren, W.; Rutten, P.; Tijssen, J.; Eijsman, L.

    2004-01-01

    Objective: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated-

  10. History and Current Status of Robotic Totally Endoscopic Coronary Artery Bypass

    National Research Council Canada - National Science Library

    Lee, Jeffrey D; Srivastava, Mukta; Bonatti, Johannes

    2012-01-01

    Robotic totally endoscopic coronary artery bypass (TECAB) is a minimally invasive endoscopic surgical approach using the daVinci robotic telemanipulation system to perform coronary artery bypass grafting on the arrested or beating heart...

  11. Symposium by NATO Defense Research Group Panel VIII on Computer-Based Instruction in Military Environments

    CERN Document Server

    Weddle, Peter

    1987-01-01

    This collection of papers is the result of a symposium sponsored by NATO's Defense Research Group Panel VIII in the Spring of 1985. The symposium came into being when it became obvious to the NATO countries that research, development and utilization of advanced technologies for training was the best means of increasing both training effectiveness and efficiency. This symposium was the second in a series of three devoted to training. The series was structured to cover all aspects of training. The first series addressed the value of training, the second one dealt with the application of training technologies and the third and last of the series focused on academic issues concerned with the effect of prior learning on subsequent learning. The fact that a major American publisher has determined that computer based instruction is the technology of greatest interest to the NATO community is not surprising. Advances in microprocessor technology have revolutionized both how and where we train. During this symposium t...

  12. PENERAPAN PENDEKATAN CINEMATHERAPY UNTUK MENINGKATKAN PERILAKU PROSOSIAL PADA SISWA KELAS VIII DI BOSOWA INTERNATIONAL SCHOOL MAKASSAR

    Directory of Open Access Journals (Sweden)

    Haeruddin Niva

    2016-06-01

    Full Text Available The objectives of the research are: (i to know the prosocial behavioral level of the students in Bosowa International School Makassar before and after giving cinematography approach, and (ii to know whether or not the approach is able to enhance the prosocial behavior of the students in Bosowa International School Makassar. The research is a quantitative research using experimental method. The research design used is quasi experimental design with non-equivalent control group design. The data collection technique applied is scale and FGD (Focus Group Discussion. The findings shows that (i the prosocial behavioral level of the students was low in pretest while after giving treatment there were significant increase to the prosocial behavior in the experimental group, and (ii the cinematography approach was able to increase the prosocial behavior of the Grade VIII students in Bosowa Internatinal School Makassar. 

  13. Naked DNA transfer of Factor VIII induced transgene-specific, species-independent immune response in hemophilia A mice.

    Science.gov (United States)

    Ye, Peiqing; Thompson, Arthur R; Sarkar, Rita; Shen, Zhenping; Lillicrap, David P; Kaufman, Randal J; Ochs, Hans D; Rawlings, David J; Miao, Carol H

    2004-07-01

    The development of antibodies to a previously unexpressed protein product may limit the success of human gene therapy approaches. We inserted B-domain-deleted factor VIII (FVIII) cDNA of human, canine, or murine origin into the multiple cloning site of a liver-specific vector, pBS-HCRHPI-A, to yield plasmids pBS-HCRHPI-FVIIIA, pBS-HCRHPI-cFVIIIA, and pBS-HCRHPI-mFVIIIA, respectively. Fifty micrograms of each plasmid in 2 ml of solution was rapidly injected into the tail vein of three groups of hemophilia A mice. Factor VIII levels ranging from 3 to 12 IU/ml were obtained from all three groups (normal is 1 IU/ml in human plasma) 3 days after treatment. These initial very high levels of functional human, canine, or murine factor VIII, however, fell gradually to undetectable levels within 2-3 weeks, and their disappearance correlated with the generation of high-titer, inhibitory anti-FVIII antibodies. Notably, this immune response occurred independent of the species of origin of the exogenous factor VIII. Antibody titers to factor VIII were detected beginning at 2 weeks, reached a plateau and remained at high levels for over 6 months. The majority of anti-hFVIII IgG was IgG1 isotype specific, suggesting a humoral response mediated by Th2-induced signals. Consistent with this idea, in a separate group of mice treated with pBS-HCRHPI-FVIIIA, transient immunosuppression by cyclophosphamide significantly delayed (5/6) or abolished (1/6) inhibitory antibody formation against the transgene.

  14. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

    Science.gov (United States)

    Al-Allaf, Faisal A.; Taher, Mohiuddin M.; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M.; Abalkhail, Halah A.; Owaidah, Tarek MA.

    2017-01-01

    Background Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. Methods For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Results Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. Conclusion The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia. PMID:28270892

  15. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies.

    Science.gov (United States)

    Al-Allaf, Faisal A; Taher, Mohiuddin M; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M; Abalkhail, Halah A; Owaidah, Tarek Ma

    2017-04-01

    Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia.

  16. [Prevalence of early and late dumping after gastric bypass].

    Science.gov (United States)

    Héraïef, R; Giusti, V

    2014-03-26

    Gastric bypass surgery is an effective treatment of obesity, bringing a significant weight loss and a major improvement of carbohydrate profile. However, in some patients, a deregulation in carbohydrate metabolism between insulin secretion and sensitivity is observed, whereupon early and late dumping happen. Their prevalence isn't well studied, although it seems that 10 to 20% of patients are affected. We've studied a cohort of 70 patients who undergone gastric bypass surgery at the CHUV. 18 (25.7%) patients have a positive anamnesis for early dumping and 10 (14.3%) for late dumping, being it superior as what is described in the literature.

  17. Construct exploit constraint in crash analysis by bypassing canary

    Science.gov (United States)

    Huang, Ning; Huang, Shuguang; Huang, Hui; Chang, Chao

    2017-08-01

    Selective symbolic execution is a common program testing technology. Developed on the basis of it, some crash analysis systems are often used to test the fragility of the program by constructing exploit constraints, such as CRAX. From the study of crash analysis based on symbolic execution, this paper find that this technology cannot bypass the canary stack protection mechanisms. This paper makes the improvement uses the API hook in Linux. Experimental results show that the use of API hook can effectively solve the problem that crash analysis cannot bypass the canary protection.

  18. Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses

    DEFF Research Database (Denmark)

    Nielsen, Tina G; Djurhuus, Christian Born; Morre-Pedersen, Erik

    1996-01-01

    Doppler spectra obtained 10 cm downstream of the fistula. All measurements were carried out with open and clamped fistula. RESULTS: At 30% diameter reducing stenosis opening of the fistula induced a 12% systolic pressure drop across the stenosis but had no adverse effect on the Doppler waveform parameters......PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced...

  19. Dextrocardia with situs inversus totalis: coronary artery bypass grafting.

    Science.gov (United States)

    Hashmi, Salila; Anis, Mariam; Darr, Umer

    2012-01-01

    Dextrocardia with situs inversus is a rare congenital abnormality involving a left-handed mal rotation of the visceral organs. The incidence of coronary artery disease is the same as that in the general population. Performing coronary artery bypass surgery on patients with dextrocardia poses a more challenging task. It is recommended that the right internal mammary artery be the first choice of graft for the anterior descending artery for a "situs inversus" situation. We report 2 cases of patients with Dextrocardia who developed coronary artery disease and underwent coronary artery bypass grafting. Also mentioned is the slight difference in our technique.

  20. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery

    Directory of Open Access Journals (Sweden)

    Harrison C Brown

    2014-01-01

    Full Text Available Clinical data support the feasibility and safety of adeno-associated viral (AAV vectors in gene therapy applications. Despite several clinical trials of AAV-based gene transfer for hemophilia B, a unique set of obstacles impede the development of a similar approach for hemophilia A. These include (i the size of the factor VIII (fVIII transgene, (ii humoral immune responses to fVIII, (iii inefficient biosynthesis of human fVIII, and (iv AAV vector immunity. Through bioengineering approaches, a novel fVIII molecule, designated ET3, was developed and shown to improve biosynthetic efficiency 10- to 100-fold. In this study, the utility of ET3 was assessed in the context of liver-directed, AAV-mediated gene transfer into hemophilia A mice. Due to the large size of the expression cassette, AAV-ET3 genomes packaged into viral particles as partial genome fragments. Despite this potential limitation, a single peripheral vein administration of AAV-ET3 into immune-competent hemophilia A mice resulted in correction of the fVIII deficiency at lower vector doses than previously reported for similarly oversized AAV-fVIII vectors. Therefore, ET3 appears to improve vector potency and mitigate at least one of the critical barriers to AAV-based clinical gene therapy for hemophilia A.

  1. Costs and utilization of hemophilia A and B patients with and without inhibitors.

    Science.gov (United States)

    Armstrong, Edward P; Malone, Daniel C; Krishnan, Sangeeta; Wessler, Maj Jacob

    2014-11-01

    To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.

  2. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy.

    Science.gov (United States)

    Peng, Baowei; Ye, Peiqing; Rawlings, David J; Ochs, Hans D; Miao, Carol H

    2009-11-12

    One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased transforming growth factor-beta levels in plasma and the frequency of both CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6 weeks after treatment protected recipient mice from anti-FVIII immune responses. Anti-CD3-treated mice mounted immune responses against both T-dependent and T-independent neo-antigens, indicating that anti-CD3 did not hamper the immune systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced long-term tolerance specific to FVIII via a mechanism involving the increase in transforming growth factor-beta levels and the generation of adaptive FVIII-specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice.

  3. On-pump versus off-pump coronary artery bypass surgery

    DEFF Research Database (Denmark)

    Houlind, Kim Christian

    2013-01-01

    Off pump coronary artery bypass surgery has been purported to be safer than conventional coronary artery bypass surgery performed using cardiopulmonary bypass. This theory was supported by a number of early series, but failed to be confirmed by a number of small, randomized controlled trials...

  4. On-Pump Versus Off-Pump Coronary Artery Bypass Surgery in Elderly Patients

    DEFF Research Database (Denmark)

    Houlind, Kim; Kjeldsen, Bo Juul; Madsen, Susanne Nørgaard

    2012-01-01

    Conventional coronary artery bypass grafting performed with the use of cardiopulmonary bypass is a well-validated treatment for patients with ischemic heart disease. Off-pump coronary artery bypass grafting (OPCAB) has been suggested to reduce the number of perioperative complications, especially...

  5. Fabrication of nanofiber non-wovens on the melt blowing die with air by-passes

    OpenAIRE

    Chen Ting; Yang Kang; Wu Li-Li

    2016-01-01

    The air flow field of the melt blowing die with air by-passes is simulated. The results show that fibers fabricated on the die with air by-passes are much finer than those without air by-passes, which indicates an energy-saving approach to fabricating nanofibers on the melt blowing equipment.

  6. Fabrication of nanofiber non-wovens on the melt blowing die with air by-passes

    Directory of Open Access Journals (Sweden)

    Chen Ting

    2016-01-01

    Full Text Available The air flow field of the melt blowing die with air by-passes is simulated. The results show that fibers fabricated on the die with air by-passes are much finer than those without air by-passes, which indicates an energy-saving approach to fabricating nanofibers on the melt blowing equipment.

  7. Natural headland sand bypassing; towards identifying and modelling the mechanisms and processes

    NARCIS (Netherlands)

    Bin Ab Razak, M.S.

    2015-01-01

    Natural headland sand bypassing: Towards identifying and modelling the mechanisms and processes contributes to the understanding of the mechanisms and processes of sand bypassing in artificial and non-artificial coastal environments through a numerical modelling study. Sand bypassing processes in

  8. 21 CFR 870.4210 - Cardiopulmonary bypass vascular catheter, cannula, or tubing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass vascular catheter, cannula... Devices § 870.4210 Cardiopulmonary bypass vascular catheter, cannula, or tubing. (a) Identification. A cardiopulmonary bypass vascular catheter, cannula, or tubing is a device used in cardiopulmonary surgery to...

  9. 21 CFR 870.4290 - Cardiopulmonary bypass adaptor, stopcock, manifold, or fitting.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass adaptor, stopcock, manifold... Devices § 870.4290 Cardiopulmonary bypass adaptor, stopcock, manifold, or fitting. (a) Identification. A cardiopulmonary bypass adaptor, stopcock, manifold, or fitting is a device used in cardiovascular diagnostic...

  10. 21 CFR 870.4340 - Cardiopulmonary bypass level sensing monitor and/or control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass level sensing monitor and... Devices § 870.4340 Cardiopulmonary bypass level sensing monitor and/or control. (a) Identification. A cardiopulmonary bypass level sensing monitor and/or control is a device used to monitor and/or control the level...

  11. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass on-line blood gas monitor. 870.4330 Section 870.4330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood gas...

  12. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass heart-lung machine console. 870.4220 Section 870.4220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine...

  13. 21 CFR 870.4270 - Cardiopulmonary bypass cardiotomy suction line blood filter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass cardiotomy suction line... Devices § 870.4270 Cardiopulmonary bypass cardiotomy suction line blood filter. (a) Identification. A cardiopulmonary bypass cardiotomy suction line blood filter is a device used as part of a gas exchange (oxygenator...

  14. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood through...

  15. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through the...

  16. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class II...

  17. Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study

    Directory of Open Access Journals (Sweden)

    Barrios Ysamar

    2007-04-01

    Full Text Available Abstract Introduction Excessive bleeding (EB after cardiopulmonary bypass (CPB may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB. Methods We performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes. Results EB incidence was 50%, associated with body mass index (BMI2, (P = 0.03, lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1 (P = 0.01, lower body temperature during CPB (P = 0.037 and at ICU admission (P = 0.029, and internal mammary artery graft (P = 0.03 in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07; P = 0.02 and temperature during CPB (F = 8.84; P = 0.007. EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (P = 0.01, P P Conclusion Excessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.

  18. Myocardial ischaemia during coronary artery bypass graft surgery: a ...

    African Journals Online (AJOL)

    Multiorgan dysfunction as a result of the effects of the neurohumoral system, triggered by surgery, anaesthesia, cardiopulmonary bypass, hypothermia and blood transfusion, can lead to prolonged intensive care unit and hospital stay. In this article, a literature review was embarked upon, to understand the pathophysiology ...

  19. Return to the workforce following coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Butt, Jawad H; Rørth, Rasmus; Kragholm, Kristian

    2018-01-01

    BACKGROUND: Returning to the workforce after coronary artery bypass grafting (CABG) holds important socioeconomic consequences not only for patients, but the society as well. Yet data on this issue are limited. We examined return to the workforce and associated factors in patients of working age...

  20. The effect of bypass protein supplementation on the reproductive ...

    African Journals Online (AJOL)

    Unknown

    Short paper and poster abstracts: 38th Congress of the South African Society of Animal Science. The South African Journal of Animal Science is available online at http://www.sasas.co.za/Sajas.html. 60. The effect of bypass protein supplementation on the reproductive performance of. Merino sheep grazing mixed karoo veld.

  1. Blood concentrations of cefuroxime in cardiopulmonary bypass surgery

    NARCIS (Netherlands)

    Bertholee, Daphne; ter Horst, Peter G. J.; Hijmering, Michel L.; Spanjersberg, Alexander J.; Hospes, Wobbe; Wilffert, Bob

    2013-01-01

    Objectives Patients with coronary artery bypass graft (CABG) surgery are at risk for severe postoperative infections. Prophylactic cefuroxime may help to reduce this risk, however sufficient concentrations, i.e. above the breakpoint (32 mg/L), are mandatory. The aim of this study is to evaluate the

  2. Angina pectoris, one to 10 years after aortocoronary bypass surgery

    NARCIS (Netherlands)

    K. Laird-Meeter; H.J. ten Katen (Harald); R.W. Brower (Ronald); M.J.B.M. van den Brand (Marcel); P.W.J.C. Serruys (Patrick); M.M.P. Haalebos (Max); E. Bos (Egbert); P.G. Hugenholtz (Paul)

    1983-01-01

    textabstractThe incidence of angina pectoris (AP) after bypass surgery was assessed in 1041 patients operated on consecutively between 1971 and 1980. Of the 977 survivors, 920 (94%) participated in the study with a followup time varying from 1 to 10 years (mean 3.5 years). Post-operative angina

  3. Positive maternal and foetal outcomes after cardiopulmonary bypass ...

    African Journals Online (AJOL)

    This case study describes the successful management of a parturient with severe mitral stenosis and moderate mitral regurgitation who underwent cardiopulmonary bypass (CPB) surgery. A healthy baby was delivered by Caesarean section 11 days later. The effects of CPB surgery and mitral valve replacement on ...

  4. Emergency bypass post percutaneous atrial ablation: a case report.

    LENUS (Irish Health Repository)

    Hargrove, M

    2010-11-01

    A 34-year-old male undergoing percutaneous atrial ablation procedure for paroxysmal fibrillation required emergency sternotomy for cardiac tamponade. The patient had been anticoagulated and had received plavix and aspirin prior to and during the ablation procedure. Seven units of red cell concentrate had been transfused in the cardiac catherisation laboratory. On arrival in theatre, the patient was hypotensive, but was awake on induction of anaesthesia. No recordable blood pressure with non-invasive monitoring was observed. A sternotomy was immediately performed and, on evacuation of the pericardium, a bleeding site was not visible. The patient was commenced on cardiopulmonary bypass. Bleeding site was identified and the defect closed. The patient was weaned from cardiopulmonary bypass with minimal inotropic support and made an uneventful recovery. Bypass time was 38 minutes. A literature review showed a 1% incidence of post-ablation bleeding(1). The incidence of reverting to bypass for such an event has not been reported previously. During these procedures, it might be wise to have the cardiothoracic team notified while atrial ablation procedures are being performed in the cardiac catheterization laboratory.

  5. Incidence and aetiology of a raised hemidiaphragm after cardiopulmonary bypass.

    Science.gov (United States)

    Large, S R; Heywood, L J; Flower, C D; Cory-Pearce, R; Wallwork, J; English, T A

    1985-01-01

    A raised hemidiaphragm has been reported as an uncommon complication of cardiopulmonary bypass, possibly resulting from cold injury to the phrenic nerve. At Papworth Hospital myocardial protection during cardiac arrest relies in part on irrigation of the pericardial cavity with large volumes of Hartmann's solution at 4 degrees C. Retrospective review of the chest radiographs of 100 consecutive patients undergoing cardiopulmonary bypass showed that 31 had a raised left hemidiaphragm soon after operation. The only significant correlation was with aortic cross clamp time (p less than 0.03). A prospective study of 36 consecutive patients undergoing cardiopulmonary bypass was then undertaken with diaphragmatic screening and chest radiography. Preoperative screening gave normal results in all patients. In the early postoperative period 16 (44%) had left diaphragmatic weakness or paralysis, two (5.5%) right sided weakness, and two (5.5%) bilateral weakness. Repeat screening of these patients showed resolution in all but four cases (80%) at six months and in all but two (90%) at one year. The greater number of left sided lesions than of right (8:1) is probably due to the fact that the cold jet of irrigating fluid is directed towards the left phrenic nerve. These findings have implications with regard to the optimum temperature of the irrigant fluid for myocardial protection during cardiopulmonary bypass. PMID:4024004

  6. Difficult Tracheal Intubation in Obese Gastric Bypass patients

    DEFF Research Database (Denmark)

    Dohrn, Niclas; Sommer, Thorbjørn; Bisgaard, J.

    2016-01-01

    undergoing gastric bypass. Tracheal intubation was done preoperatively together with scoring of Intubation Score (IS), Mallampati (MLP), and Cormack-Lehane classification (CLC) and registration of the quantities of anesthetics and total attempts on cannulation. The overall proportion of patients with DTI...

  7. Bypassing of a barrier by dissociated and superlattice dislocations

    DEFF Research Database (Denmark)

    Bhushan, Karihaloo

    1975-01-01

    Very simple procedures are used to calculate the upper and lower bounds for the applied stress required for the leading extended (superlattice) dislocation in a group of n coplanar screw dislocations of like sign with Burgers vector b to bypass a noncoplanar perfect screw dislocation with Burgers...

  8. Gastrointestinal motility during cardiopulmonary bypass : A sonomicrometric study

    NARCIS (Netherlands)

    Gu, YJ; de Kroon, TL; Elstrodt, JM; Rakhorst, G

    Cardiopulmonary bypass (CPB) is known to impair the integrity of the gastrointestinal tract. However, little is known about the movement behavior of the gastrointestinal tract during CPB. This study was aimed to assess the gastrointestinal motility with sonomicrometry, a distance measurement using

  9. Differential effects of gastric bypass and banding on the ...

    African Journals Online (AJOL)

    Hala Mourad Demerdash

    2012-09-01

    Sep 1, 2012 ... Abstract Background: Weight loss (5–10%) improves obesity-associated cardiovascular risk factors. The aim of this work was to study the effect of 2 commonly performed bariatric surgical procedures; laparoscopic Roux-en-Y gastric bypass (RYGBP) and laparoscopic gastric band. (BAND), on the ...

  10. Differential effects of gastric bypass and banding on the ...

    African Journals Online (AJOL)

    Background: Weight loss (5–10%) improves obesity-associated cardiovascular risk factors. The aim of this work was to study the effect of 2 commonly performed bariatric surgical procedures; laparoscopic Roux-en-Y gastric bypass (RYGBP) and laparoscopic gastric band (BAND), on the cardiovascular risk profile in ...

  11. Combined Open-Heart Coronary Artery Bypass Surgery and ...

    African Journals Online (AJOL)

    CASE DETAILS: A 54-year-old woman suffering from dyspnea, chest pain and decreased left ventricular function (EF=40%) was diagnosed with coronary artery disease (3 vessel disease) and became candidate for coronary artery bypass grafting (CABG). Also, she had multinodular goiter with normal thyroid function test.

  12. Predicting the need for blood during cardiopulmonary bypass ...

    African Journals Online (AJOL)

    Methods: An equation for prediction of HctCPB (Hctpred), based on weight and pre-operative haemoglobin concentration was used to forecast which patients would develop HctCPB < 20%. ... Key Words: Haematocrit, Blood transfusion, Autologous, Cardiopulmonary bypass, ROC curve, Predictive value of tests. Southern ...

  13. A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19ARF-p53 signaling

    NARCIS (Netherlands)

    Shvarts, A.; Brummelkamp, T.; Koh, E.; Daley, G.Q.; Bernards, R.A.

    2002-01-01

    Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

  14. A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling

    NARCIS (Netherlands)

    Shvarts, Avi; Brummelkamp, Thijn R.; Scheeren, Ferenc; Koh, Eugene; Daley, George Q.; Spits, Hergen; Bernards, René

    2002-01-01

    Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

  15. Bypass Surgery after Endovascular Therapy for Infrapopliteal Lesion Is Not a Poor Outcome Compared with Initial Bypass Surgery by Vascular Surgeons.

    Science.gov (United States)

    Morisaki, Koichi; Yamaoka, Terutoshi; Iwasa, Kazuomi; Ohmine, Takahiro

    2017-11-01

    It is unclear whether prior endovascular therapy (EVT) adversely affects bypass surgery. The aim of this study is to investigate treatment outcomes between initial bypass (bypass-first) and bypass surgery after EVT (EVT-first). We conducted a retrospective analysis of critical limb ischemia patients undergoing infrapopliteal bypass between November 2006 and December 2015. Graft patency, limb salvage (LS), amputation-free survival (AFS), and overall survival (OS) were examined between bypass-first and EVT-first groups. The subjects in this study were 75 patients and 82 limbs in the bypass-first group and 24 patients and 24 limbs in the EVT-first group. The average age was higher in EVT-first group (P = 0.03). The percentage of inframalleolar bypass was higher in the EVT-first group (P = 0.002). Primary patency at 1 and 2 years was 72.0% and 67.5% for the bypass-first group and 53.1% and 47.2% for the EVT-first group, respectively (P = 0.04). Inframalleolar bypass was a risk factor for lower primary patency (hazard ratio 3.07, 95% confidence interval 1.18-8.51, P = 0.02) in multivariate analysis, while there were no differences in secondary patency, LS, AFS, and OS. Bypass surgery after EVT has lower primary patency rates in comparison with primary bypass in patients submitted to infrapopliteal revascularization. Although very heterogeneous study population with a lot of bias in the indication of the revascularization, LS, OS and AFS are not affected by previous EVT. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure

    Directory of Open Access Journals (Sweden)

    Nelson Américo Hossne Junior

    2015-08-01

    Full Text Available Abstract Objective: Coronary artery bypass grafting is currently the best treatment for dialysis patients with multivessel coronary artery involvement. Vasoplegic syndrome of inflammatory etiology constitutes an important postoperative complication, with highly negative impact on prognosis. Considering that these patients have an intrinsic inflammatory response exacerbation, our goal was to evaluate the incidence and mortality of vasoplegic syndrome after myocardial revascularization in this group. Methods: A retrospective, single-center study of 50 consecutive and non-selected dialysis patients who underwent myocardial revascularization in a tertiary university hospital, from 2007 to 2012. The patients were divided into 2 groups, according to the use of cardiopulmonary bypass or not (off-pump coronary artery bypass. The incidence and mortality of vasoplegic syndrome were analyzed. The subgroup of vasoplegic patients was studied separately. Results: There were no preoperative demographic differences between the cardiopulmonary bypass (n=20 and off-pump coronary artery bypass (n=30 group. Intraoperative data showed a greater number of distal coronary arteries anastomosis (2.8 vs. 1.8, P<0.0001 and higher transfusion rates (65% vs. 23%, P=0.008 in the cardiopulmonary bypass group. Vasoplegia incidence was statistically higher (P=0.0124 in the cardiopulmonary bypass group (30% compared to the off-pump coronary artery bypass group (3%. Vasoplegia mortality was 50% in the cardiopulmonary bypass group and 0% in the off-pump coronary artery bypass group. The vasoplegic subgroup analysis showed no statistically significant clinical differences. Conclusion: Cardiopulmonary bypass increased the risk for developing postoperative vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure.

  17. Comparison of 4% Succinylated Gelatin with 6% Hydroxyethyl Starch 130/0.4 for Preloading Prior to Cardiopulmonary Bypass in Coronary Artery Bypass Grafting Patients

    OpenAIRE

    Deshmukh, Amit; Dave, Sona; Gujjar, Pinakin

    2016-01-01

    Aims and Objective: The present study was carried out with an objective to compare 4% succinylated gelatin with 6% hydroxyethyl starch 130/0.4 for preloading prior to cardiopulmonary bypass in coronary artery bypass grafting patients with respect to haemodynamics status, blood loss, transfusion requirement, ICU stay and complication. Methods: The study enrolling 60 patients of either sex, aged between 30-70 years undergoing elective coronary artery bypass grafting. These patients were randoml...

  18. PENGEMBANGAN MODEL PEMBELAJARAN BERBASIS MASALAH YANG BERMUATAN NILAI-NILAI PENDIDIKAN KARAKTER DALAM PEMBELAJARAN MENULIS CERPEN PADA KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Aditya Dwi Haryawan

    2014-08-01

    Full Text Available Menulis merupakan suatu keterampilan yang harus dimiliki peserta didik sekolah menengah pertama. Melaluitulisan, peserta didik dapat menyampaikan pengalaman, pikiran, perasaan, atau keinginan. Masalah penelitianini adalah (1 bagaimanakah kebutuhan pengembangan model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen berdasarkan persepsi guru dan pesertadidik kelas VIII SMP?; (2 bagaimanakah prinsip-prinsip pengembangan model pembelajaran berbasis masalahyang bermuatan nilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada peserta didik kelasVIII SMP? (3 bagaimanakah pengembangan prototipe model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP?; (4 bagaimanakahkeberterimaan penerapan pengembangan model pembelajaran berbasis masalah yang bermuatan nilai-nilaipendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP. Dalam penelitian ini digunakandesain Research and Development. Tahapan yang dilakukan dalam penelitian ini adalah studi pustaka, analisiskebutuhan, pengembangan model yang dikembangkan, uji validasi, revisi, implementasi, revisi akhir,pengembangan model/produk akhir. Pengumpulan data dilakukan dengan observasi, angket, wawancara, tes,dan dokumentasi foto. Writing is a skill that must be owned by middle school students. Through writing, students canconvey experiences, thoughts, feelings, or desires. The research problem is (1 How can the needsof the development of PBL model that charged the values of character education in learning towrite short stories on the perceptions of teachers and students of class VIII?; (2 How do thecharacteristics of the development of PBL model value-laden -the value of character education inlearning to write short stories at the high school of learner assessment system class?; (3 How isthe development of a prototype model of PBL  charged

  19. Prevention of inhibitor development in hemophilia A in 2016. A glimpse into the future?

    Science.gov (United States)

    Franchini, Massimo; Lippi, Giuseppe

    2016-12-01

    Thanks to considerable progresses made over the last 30years, hemophilia benefits from the most efficacious and safe treatment among the many monogenic inherited disorders. The most challenging complication of replacement therapy in hemophilia A is the occurrence of alloantibodies against infused factor VIII (FVIII), thus predisposing the patients to increased morbidity and disability. Extensive research in this field has definitively unraveled that development of inhibitors in hemophilia A is a complex and multifactorial process, in which inherited and environmental factors dynamically interact. This narrative review, after providing a concise overview about the main genetic and non-genetic risk factors, is aimed to focus on prediction risk models and preventive strategies for minimizing the risk of developing inhibitors in hemophilia A patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Shoulder arthroplasty following gastric bypass, do complications follow?

    Science.gov (United States)

    Schoch, Bradley S; Aibinder, William R; Werthel, Jean-David; Sperling, John W; Sanchez-Sotelo, Joaquin; Cofield, Robert H

    2018-02-01

    Previous reports have shown an increased risk of complications after arthroplasty in the obese population. It remains unclear if gastric bypass surgery prior to shoulder arthroplasty modifies the complication and failure rate. The purpose of this study is to assess the complication and re-operation rates following shoulder arthroplasty in this population. Between 2002 and 2012, 39 shoulders with prior gastric bypass underwent shoulder arthroplasty (3 HA, 16 TSA, 20 RSA). The mean time from the gastric bypass to arthroplasty was 13 years (range, 0.7-32). Shoulders were followed for a minimum of two years (mean, 3.8 years) or until re-operation. Outcome measures included pain, range of motion, satisfaction, modified Neer ratings, and ASES scores. Complications occurred in seven shoulders (18%), with five requiring re-operation. There was no common failure mechanism. Re-operations occurred for aseptic glenoid loosening, periprosthetic fracture, and unexplained pain. Those shoulders with complications were similar to those without in regard to age, sex, and BMI. Complications were more common following anatomic arthroplasty compared to reverse arthroplasty (5 vs 1, p = 0.06); however, complications were not improved compared to historical controls with morbid obesity. Overall, pain improved significantly from 4.8 pre-operatively to 2.3 postoperatively (p bypass surgery prior to shoulder arthroplasty leads to clinical improvement in both pain and range of motion. Prior gastric bypass surgery does not result in a lower surgical complication rate compared to previously published reports in the morbidly obese population. Level 4, case series.

  1. Cancer incidence and mortality after gastric bypass surgery.

    Science.gov (United States)

    Adams, Ted D; Stroup, Antoinette M; Gress, Richard E; Adams, Kenneth F; Calle, Eugenia E; Smith, Sherman C; Halverson, R Chad; Simper, Steven C; Hopkins, Paul N; Hunt, Steven C

    2009-04-01

    Despite weight loss recommendations to prevent cancer, cancer outcome studies after intentional weight loss are limited. Recently, reduced cancer mortality following bariatric surgery has been reported. This study tested whether reduced cancer mortality following gastric bypass was due to decreased incidence. Cancer incidence and mortality data through 2007 from the Utah Cancer Registry (UCR) were compared between 6,596 Utah patients who had gastric bypass (1984-2002) and 9,442 severely obese persons who had applied for Utah Driver's Licenses (1984-2002). Study outcomes included incidence, case-fatality, and mortality for cancer by site and stage at diagnosis of all gastric bypass patients, compared to nonoperated severely obese controls. Follow-up was over a 24-year period (mean 12.5 years). Total cancer incidence was significantly lower in the surgical group compared to controls (hazard ratio (HR) = 0.76; confidence interval (CI) 95%, 0.65-0.89; P = 0.0006). Lower incidence in surgery patients vs. controls was primarily due to decreased incidence of cancer diagnosed at regional or distant stages. Cancer mortality was 46% lower in the surgery group compared to controls (HR = 0.54; CI 95%, 0.37-0.78; P = 0.001). Although the apparent protective effect of surgery on risk of developing cancer was limited to cancers likely known to be obesity related, the inverse association for mortality was seen for all cancers. Significant reduction in total cancer mortality in gastric bypass patients compared with severely obese controls was associated with decreased incidence, primarily among subjects with advanced cancers. These findings suggest gastric bypass results in lower cancer risk, presumably related to weight loss, supporting recommendations for reducing weight to lower cancer risk.

  2. Intraoperative Eptifibatide Administration During Urgent Arterial Bypass in Neurosurgery.

    Science.gov (United States)

    Stambolija, Vasilije; Mrak, Goran; Lozic, Marin; Ljevak, Josip; Miklic Bublic, Martina; Scap, Miroslav

    2017-07-01

    In some cases when risk of occlusion of a blood vessel is greater than risk of bleeding when patients undergo urgent or unplanned bypass during neurosurgery, the use of eptifibatide may be an option. We describe 2 patients who underwent arterial bypass in whom eptifibatide was used successfully intraoperatively during neurosurgery for prevention of bypass occlusion. The first patient presented with a right middle cerebral artery (MCA) aneurysm with subocclusive stenosis of the M1 branch. After right-sided osteoplastic frontotemporal craniotomy, the MCA bifurcation was exposed with a bifurcational 6-mm aneurysm with a wide neck. Prebifurcation stenosis was found, with yellow calcification of the vessel wall, and postbifurcation calcification was found on the upper M2 branch. Superficial temporal artery-MCA bypass and occlusion of the MCA aneurysm was done. Before the bypass, continuous intravenous infusion of eptifibatide 1 μg/kg/minute was administered. The patient recovered normally without hemorrhage or neurologic deficit. The second patient presented with a left-sided lateral sphenoid wing meningioma. Left-sided frontotemporal craniotomy was performed, and the tumor was completely removed from the arachnoid layer. The temporal M3 branch was invaded by the meningioma. As there was no flow through the invaded segment of the aforementioned artery, termino-terminal M3 arterial anastomosis was done. Continuous intravenous infusion of eptifibatide 1 μg/kg/minute was administered. Indocyanine green angiography showed normal flow through the anastomosis, and the patient recovered normally. Future studies are needed to test the safety and potential efficacy of eptifibatide in intraoperative settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Validation of viscoelastic coagulation tests during cardiopulmonary bypass.

    Science.gov (United States)

    Ortmann, E; Rubino, A; Altemimi, B; Collier, T; Besser, M W; Klein, A A

    2015-07-01

    Viscoelastic point-of-care tests such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are increasingly used to guide hemostatic therapy after cardiac surgery. The aim of this study was to assess their clinical utility during cardiopulmonary bypass to predict postbypass coagulation status and to guide therapy. In this prospective study, TEG and ROTEM tests were performed in 52 adult patients undergoing elective cardiac surgery at two time points: near the end of cardiopulmonary bypass and after heparin reversal with protamine. The 95% confidence intervals of the mean difference were compared with a prespecified clinically relevant limit of ± 20% of the value after protamine. Both viscoelastic fibrinogen assays were well within the prespecified clinically relevant limit (≥ 79% of patients). The laboratory Clauss fibrinogen was much lower during cardiopulmonary bypass than after protamine (mean difference 1.2 g L(-1) , 95% CI 1.03-1.4, which was outside a clinically acceptable difference. For intrinsically activated tests, clotting times (CT) were different and outside the prespecified limit on TEG (mean difference -1.2 min, 95% CI -1.8 to -0.6) but not on ROTEM (mean difference 2.3 sec, 95% CI -8.6 to 13.2), while clot strength was well within the clinical limit on both devices (≥ 94% of patients). For extrinsically activated tests, clot strength on both TEG and ROTEM was within the pre-specified limit in 98% of patients. Results from TEG and ROTEM tests performed toward the end of cardiopulmonary bypass are similar to results after reversal of heparin. Amplitudes indicating clot strength were the most stable parameters across all tests, whereas CT showed more variability. In contrast, laboratory testing of fibrinogen using the Clauss assay was essentially invalid during cardiopulmonary bypass. © 2015 International Society on Thrombosis and Haemostasis.

  4. Cold agglutinins in patients undergoing cardiac surgery requiring cardiopulmonary bypass.

    Science.gov (United States)

    Barbara, David W; Mauermann, William J; Neal, James R; Abel, Martin D; Schaff, Hartzell V; Winters, Jeffrey L

    2013-09-01

    Cold agglutinins (CA) are circulating autoantibodies present in most humans. They are active below normal body temperatures. Cold hemagglutinin disease involves the presence of CA sufficiently active at temperatures in the periphery to produce hemolysis or agglutination. Systemic hypothermia and cold cardioplegia may result in agglutination or hemolysis. We reviewed the experience of a large referral center in managing patients with CA and cold hemagglutinin disease undergoing cardiac surgery requiring cardiopulmonary bypass. The electronic medical records from 2002 to 2010 were searched to identify patients with CA or cold hemagglutinin disease who underwent cardiac surgery requiring cardiopulmonary bypass. Information related to preoperative CA testing and treatment, surgery, cardiopulmonary bypass, postoperative complications, and mortality was recorded. Sixteen patients underwent 19 procedures requiring cardiopulmonary bypass. Six patients had cold hemagglutinin disease. The identification of CA was made intraoperatively in 3 patients. One patient underwent preoperative plasma exchange. Cold blood cardioplegia was used in 2 of 16 procedures using cardioplegia, with the remaining using warmer blood cardioplegia. The lowest recorded intraoperative core temperature was less than 34 °C in 1 case. CA-related postoperative hemolysis requiring transfusion was present in 1 patient, which was resolved with active warming. No patient had evidence of permanent myocardial dysfunction, had a neurologic event, required dialysis, or died within 30 days. All patients with CA/cold hemagglutinin disease at the Mayo Clinic College of Medicine safely underwent cardiac surgery without major adverse morbidity or mortality. Patients with CA but without evidence of cold hemagglutinin disease can safely undergo normothermic cardiopulmonary bypass at 37°C and warm cardioplegia without further testing. Patients with cold hemagglutinin disease should undergo laboratory testing including

  5. The scientific evidence of arterial line filtration in cardiopulmonary bypass.

    Science.gov (United States)

    Johagen, Daniel; Svenmarker, Staffan

    2016-09-01

    The indication for arterial line filtration (ALF) is to inhibit embolisation during cardiopulmonary bypass. Filtration methods have developed from depth filters to screen filters and from a stand-alone component to an integral part of the oxygenator. For many years, ALF has been a standard adopted by a majority of cardiac centres worldwide. The following review aims to summarize the available evidence in support for ALF and report on its current practice in Europe. The principles and application of ALF in Europe was investigated using a survey conducted in 2014. The scientific evidence for ALF was examined by performing a systematic literature search in six different databases, using the following search terms: "Cardiopulmonary bypass AND filters AND arterial". The primary endpoint was protection against cerebral injury verified by the degree of cerebral embolisation or cognitive tests. The secondary endpoint was improvement of the clinical outcome verified elsewise. Only randomised clinical trials were considered. The response rate was 31% (n=112). The great majority (88.5%) of respondents were using ALF, following more than 10 years of experience. Integrated arterial filtration was used by 55%. Of respondents not using ALF, fifty-four percent considered starting using integrated arterial filtration. The systematic literature database search returned 180 unique publications where 82 were specifically addressing ALF in cardiopulmonary bypass. Only four out of the 82 identified publications fulfilled our inclusion criteria. Of these, three were more than 20 years old and based on the use of bubble oxygenation. ALF is a standard implemented in a majority of cardiopulmonary bypass procedures in Europe. The level of scientific evidence available in support of current arterial line filtration methods in cardiopulmonary bypass is, however, poor. Large, well-designed, randomised trials are warranted. © The Author(s) 2015.

  6. Intraoperative Evaluation of Reverse Bypass Using a Naturally Formed "Bonnet" Superficial Temporal Artery: Technical Note.

    Science.gov (United States)

    Nagm, Alhusain; Horiuchi, Tetsuyoshi; Hasegawa, Takatoshi; Hongo, Kazuhiro

    2016-04-01

    In reverse bypass that used a naturally formed "bonnet" superficial temporal artery, intraoperative volume flow measurement quantifies flow augmentation after revascularization, confirms flow preservation, and identifies inadvertent vessel compromise. A 75-year-old man presented with transient ischemic attacks attributed to right internal carotid artery stenosis. He underwent successful reverse bypass via a naturally formed "bonnet" superficial temporal artery middle cerebral artery bypass. As the result of proper intraoperative volume flow evaluation, a successful reverse bypass was achieved. Modification of the intraoperative stroke risk and prediction of the long-term patency after reverse bypass can be achieved by meticulous intraoperative blood flow evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Platelet hyperreactivity in response to on- and off-pump coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Bochsen, Louise; Rosengaard, Lisbeth Bredahl; Nielsen, Allan Bybeck

    2009-01-01

    Hypercoagulability has been reported after off-pump coronary artery bypass grafting (OPCAB) compared with patients undergoing standard coronary artery bypass grafting (CABG) with cardiopulmonary bypass. The aim of this study was to evaluate the changes in platelet reactivity in response to cardiac...... and this study identified 23% of patients needing coronary bypass surgery to be at high risk for recurrent ischemic events at 1 month after surgery, based on the MA. These results suggest that a more aggressive antithrombotic treatment might be warranted for patients undergoing coronary artery bypass grafting...

  8. DPP-4 inhibitors

    DEFF Research Database (Denmark)

    Deacon, Carolyn F.

    2016-01-01

    Dipeptidyl peptidase (DPP)-4 inhibitors inhibit the activity of the enzyme responsible for the initial rapid degradation of the incretin hormones, thereby enhancing their antihyperglycemic effects.......Dipeptidyl peptidase (DPP)-4 inhibitors inhibit the activity of the enzyme responsible for the initial rapid degradation of the incretin hormones, thereby enhancing their antihyperglycemic effects....

  9. Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers.

    Science.gov (United States)

    Fuse, Miho J; Okada, Koutaroh; Oh-Hara, Tomoko; Ogura, Hayato; Fujita, Naoya; Katayama, Ryohei

    2017-10-01

    Neurotrophic receptor tyrosine kinase 1 ( NTRK1 ) gene rearrangement leads to constitutive activation of NTRK1, which induces high-transforming ability. NTRK-rearranged cancers have been identified in several cancer types, such as glioblastoma, non-small cell lung cancer, and colorectal cancer. Although there are currently no clinically approved inhibitors that target NTRK1, several tyrosine kinase inhibitors (TKI), such as entrectinib and LOXO-101, are in clinical trials. The purpose of this study was to identify potential mechanisms of resistance to NTRK inhibitors and find potential therapeutic strategies to overcome the resistance. We examined the sensitivity of TPM3-NTRK1-transformed Ba/F3 cells and TPM3-NTRK1-harboring KM12 cells to multiple NTRK inhibitors. Acquired NTRK inhibitor-resistant mutations were screened by N-ethyl-N-nitrosourea mutagenesis with Ba/F3-TPM3-NTRK1 cells or by the establishment of NTRK-TKI-resistant cells from KM12 cells continuously treated with NTRK-TKIs. We identified multiple novel NTRK-TKI resistance mutations in the NTRK1 kinase domain, including G595R, and insulin growth factor receptor type 1 (IGF1R) bypass pathway-mediated resistance. After identifying the resistance mechanisms, we performed drug screening with small-molecule inhibitors to overcome the resistance. As a result, we found that ponatinib and nintedanib effectively inhibited the survival of TPM3-NTRK1-G667C but not G595R mutants, both of which showed resistance to entrectinib or larotrectinib (LOXO-101). Furthermore, cabozantinib with an IGF1R inhibitor such as OSI-906 could overcome bypass pathway-mediated resistance. We developed a comprehensive model of acquired resistance to NTRK inhibitors in cancer with NTRK1 rearrangement and identified cabozantinib as a therapeutic strategy to overcome the resistance. Mol Cancer Ther; 16(10); 2130-43. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Rural health care bypass behavior: how community and spatial characteristics affect primary health care selection.

    Science.gov (United States)

    Sanders, Scott R; Erickson, Lance D; Call, Vaughn R A; McKnight, Matthew L; Hedges, Dawson W

    2015-01-01

    (1) To assess the prevalence of rural primary care physician (PCP) bypass, a behavior in which residents travel farther than necessary to obtain health care, (2) To examine the role of community and non-health-care-related characteristics on bypass behavior, and (3) To analyze spatial bypass patterns to determine which rural communities are most affected by bypass. Data came from the Montana Health Matters survey, which gathered self-reported information from Montana residents on their health care utilization, satisfaction with health care services, and community and demographic characteristics. Logistic regression and spatial analysis were used to examine the probability and spatial patterns of bypass. Overall, 39% of respondents bypass local health care. Similar to previous studies, dissatisfaction with local health care was found to increase the likelihood of bypass. Dissatisfaction with local shopping also increases the likelihood of bypass, while the number of friends in a community, and commonality with community reduce the likelihood of bypass. Other significant factors associated with bypass include age, income, health, and living in a highly rural community or one with high commuting flows. Our results suggest that outshopping theory, in which patients bundle services and shopping for added convenience, extends to primary health care selection. This implies that rural health care selection is multifaceted, and that in addition to perceived satisfaction with local health care, the quality of local shopping and levels of community attachment also influence bypass behavior. © 2014 National Rural Health Association.

  11. Six amino acid residues in a 1200 A2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.

    Directory of Open Access Journals (Sweden)

    Jasper C Lin

    Full Text Available The development of neutralizing anti-factor VIII (FVIII antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200 plus two non-contiguous arginines (FVIII-R2215 and R2220, contributed appreciably to the affinity. B-domain-deleted (BDD FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.

  12. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight®), in patients with hemophilia A.

    Science.gov (United States)

    Jiménez-Yuste, V; Lejniece, S; Klamroth, R; Suzuki, T; Santagostino, E; Karim, F A; Saugstrup, T; Møss, J

    2015-03-01

    Turoctocog alfa (NovoEight(®)) is a human recombinant coagulation factor VIII (rFVIII) for the treatment of patients with hemophilia A. To evaluate the pharmacokinetics of turoctocog alfa in all age groups across clinical trials. Data from previously treated patients with severe hemophilia A (FVIII activity level of ≤ 1%) with no history of FVIII inhibitors, in a non-bleeding state, were included. The pharmacokinetics were assessed following a wash-out period and a subsequent single intravenous 50 IU kg(-1) dose of turoctocog alfa. Blood was sampled during a 48-h period postdose. Standard pharmacokinetic (PK) parameters were estimated on the basis of plasma FVIII activity vs. time (PK profiles) with non-compartmental methods. Furthermore, a population PK analysis was conducted. Data from 76 patients (aged 1-60 years) enrolled globally across six clinical trials were included, totaling 105 turoctocog alfa PK profiles. Single-dose PK results 3-6 months after the first dose of turoctocog alfa were comparable with the results obtained after the first dose. Similar PK characteristics were shown for different lots and strengths of the drug product. Overall, area under the plasma concentration (activity) curve from administration to infinity (AUC) and t1(/2) tended to increase with increasing age, with lower AUC and shorter t(1/2) being seen in children than in adolescents and adults. The PK profiles of turoctocog alfa and other commercially available plasma-derived FVIII and rFVIII products were similar in all age groups. The PK characteristics of turoctocog alfa have been thoroughly studied, and shown to be consistent over time, reproducible between different lots and strengths of drug product, and similar to those observed for other FVIII products. © 2014 International Society on Thrombosis and Haemostasis.

  13. Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy

    Science.gov (United States)

    Xu, Lingfei; Nichols, Timothy C.; Sarkar, Rita; McCorquodale, Stephanie; Bellinger, Dwight A.; Ponder, Katherine P.

    2005-01-01

    Hemophilia A (HA) is a bleeding disorder caused by factor VIII (FVIII) deficiency. FVIII replacement therapy can reduce bleeding but is expensive, inconvenient, and complicated by development of antibodies that inhibit FVIII activity in 30% of patients. Neonatal hepatic gene therapy could result in continuous secretion of FVIII into blood and might reduce immunological responses. Newborn HA mice and dogs that were injected i.v. with a retroviral vector (RV) expressing canine B domain-deleted FVIII (cFVIII) achieved plasma cFVIII activity that was 139 ± 22% and 116 ± 5% of values found in normal dogs, respectively, which was stable for 1.5 yr. Coagulation tests were normalized, no bleeding had occurred, and no inhibitors were detected. This is a demonstration of long-term fully therapeutic gene therapy for HA in a large animal model. Desmopressin (DDAVP; 1-deamino-[d-Arg8]vasopressin) is a drug that increases FVIII activity by inducing release of FVIII complexed with von Willebrand factor from endothelial cells. It has been unclear, however, if the FVIII is synthesized by endothelial cells or is taken up from blood. Because the plasma cFVIII in these RV-treated dogs derives primarily from transduced hepatocytes, they provided a unique opportunity to study the biology of the DDAVP response. Here we show that DDAVP did not increase plasma cFVIII levels in the RV-treated dogs, although von Willebrand factor was increased appropriately. This result suggests that the increase in FVIII in normal dogs after DDAVP is due to release of FVIII synthesized by endothelial cells. PMID:15837921

  14. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.

    Science.gov (United States)

    Saxena, K; Lalezari, S; Oldenburg, J; Tseneklidou-Stoeter, D; Beckmann, H; Yoon, M; Maas Enriquez, M

    2016-09-01

    BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies. To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments. In LEOPOLD I (ClinicalTrials.gov identifier, NCT01029340), males aged 12-65 years with severe haemophilia A and ≥150 exposure days received BAY 81-8973 20-50 IU kg(-1) two or three times per week for 12 months. Potency was based on chromogenic substrate assay per European Pharmacopoeia and label adjusted to mimic one-stage assay potency. Patients were randomized for potency sequence and crossed over potency groups after 6 months, followed by an optional 12-month extension. Primary efficacy endpoint was annualized bleeding rate (ABR). Patients also received BAY 81-8973 during major surgeries. Sixty-two patients received BAY 81-8973 prophylaxis and were included in the analysis. Median ABR was 1.0 (quartile 1, 0; quartile 3, 5.1) without clinically relevant differences between potency periods. Median ABR was similar for twice-weekly vs. three times-weekly dosing (1.0 vs. 2.0). Haemostasis was maintained during 12 major surgeries. Treatment-related adverse event (AE) incidence was ≤7% overall; no patient developed inhibitors. One patient with risk factors for cardiovascular disease developed a myocardial infarction. BAY 81-8973 was efficacious in preventing and treating bleeding episodes, irrespective of the potency assignment method, with few treatment-related AEs. Caution should be used when treating older patients with cardiovascular risk factors. © 2016 Bayer. Haemophilia Published by John Wiley & Sons Ltd.

  15. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  16. ANALISIS KEMAMPUAN BERPIKIR ALJABAR DALAM MATEMATIKA PADA SISWA SMP KELAS VIII

    Directory of Open Access Journals (Sweden)

    Ahmad Badawi

    2017-03-01

    Full Text Available Berpikir aljabar merupakan representasi dari aktivitas maupun kemampuan dalam mempelajari aljabar sekolah. Tujuan penelitian ini adalah untuk mengetahui kemampuan berpikir aljabar siswa SMP Kelas VIII. Metode penelitian yang digunakan adalah dengan pendekatan deskriptif kualitatif. Penelitian ini dilakukan dengan memberikan tes kemampuan berpikir aljabar pada siswa. Selanjutnya berdasarkan hasil tes, siswa dikelompokkan berdasarkan kemampuan berpikir aljabar mereka yang terdiri dari kelompok tingkat tinggi, kelompok tingkat sedang, dan kelompok tingkat rendah. Dari masing-masing kelompok tersebut dipilih dua subjek sebagai perwakilan untuk diwawancara lebih lanjut terkait kemampuan berpikir aljabar mereka. Hasil analisis dari penelitian ini menunjukkan bahwa kemampuan generasional, transformasional, dan level-meta global sudah terlihat pada sebagian siswa kelas VIII. Siswa yang termasuk dalam kelompok tingkat tinggi mempunyai kemampuan generasional, transformasional, dan level-meta global yang cenderung tinggi. Sedangkan siswa dalam kelompok rendah mempunyai kemampuan transformasional yang cenderung rendah, kemampuan generasional yang rendah sampai sedang, dan kemampuan level-meta global yang rendah sampai sedang.   Algebraic thinking is a representation of activities and abilities to learn school algebraic. The aim of this research was to determine the ability of eighth grade junior high school students in algebraic thinking. The method used in this research was the qualitative descriptive approach. This research was conducted with giving a test of algebraic thinking skills to the students. Furthermore, based on test results, students are grouped according to their algebraic thinking skills which consists of a high­level group, moderate­level group and low­level group. From each group, two subjects were selected to be interviewed more related their algebraic thinking skills, as a representative for their each group. Analytical results from

  17. PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

    Directory of Open Access Journals (Sweden)

    Apri Dwi Astuti

    2012-10-01

    Full Text Available Kemandirian belajar membantu siswa untuk bertanggung jawab dan menumbuhkan kesadaran belajar. Penggunaan uang saku menumbuhkan jiwa mandiri, jujur dan komitmen. Adapun hasil observasi awal menunjukkan masih ada siswa kels VII dan VIII SMP Semesta untuk kompetensi dasar ekonomi dibawah KKM. Tujuan penelitian ini untuk mengetahui pengaruh kemandirian belajar dn penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta. Populasi penelitian ini adalah semua siswa kelas VII dan VIII SMP Semesta Boarding School Semarang. Variabel penelitian ini adalah kemandirian belajar dan penggunaan uang saku sebagai variabel bebas, sedangkan untuk� variabel terikat adalah prestasi belajar kompetensi dasar ekonomi. Data diambil dengan metode wawancara, kuesioner dan dokumentasi guru. Analisis data menggunakan analisis regresi linear berganda.Berdasarkan penelitian secara simultan menunjukkan adanya pengaruh antara kemandirian belajar dan penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 51,3%. Secara parsial, pengaruh kemandirian belajar terhadap prestasi belajar kompetensi dasar ekonomi sebesar 66,2% dan pengaruh penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 62,5%.Berdasarkan hasil penelitian diatas disimpulkan bahwa kemandirian belajar dan penggunaan uang saku berpengaruh positif baik secara simultan maupun parsial terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta Boarding school semarang tahun pelajaran 2011/2012. Saran yang berkaitan dengan penelitian ini yaitu : 1 Sekolah disarankan untuk memberikan batasan siswa pulang ke rumah agar dapat membantu siswa beradaptasi dengan cepat dan mudah tinggal di asrama. 2 Orang tua disarankan untuk memberikan uang saku yang disesuaikan dengan kebutuhan siswa. 3 Siswa disarankan untuk meningkatkan kemandirian dalam aspek belajar terutama bagi mata pelajaran yang masih kurang dari

  18. [Detection of hemophilia A carriers by PCR analysis of hind III polymorphism in the factor VIII gene].

    Science.gov (United States)

    Wu, S; Li, Y; Cui, H; Xie, Y; Zheng, J; Pan, X; Zhang, H; Zhao, R; Zhang, Q

    1998-04-10

    To explore a scheme of using PCR analysis in the detection of carriers of Hind III polymorphism of factor VIII gene of hemophilia A. Implicating intron 19 of the factor VIII gene of 6 patients with the hemophilia A and 207 unrelated X-chromosomes were amplified by PCR and were analysed by means of Amp-RFLPs of Hind III. The incidence of the polymorphic Hind III sites in the given population was found to be 0.29. The frequence of the Hind III heterozygotes in women calculated according to Hardy-Weinberg equation was 0.41, which proved to be informative enough for carrier detection and prenatal diagnosis of hemophilia A. 2 out of 6 families (33%)examined in this study were informative. The new scheme proved to be effective for hemophilia A carrier detection and prenatal diagnosis.

  19. Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells.

    Science.gov (United States)

    Peyron, Ivan; Hartholt, Robin B; Pedró-Cos, Laura; van Alphen, Floris; Ten Brinke, Anja; Lardy, Neubury; Meijer, Sander; Voorberg, Jan

    2017-10-12

    The development of anti-factor VIII antibodies represents a major complication in the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4+ T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4+ T cells, we previously developed a mass-spectrometry based method to identify factor VIII derived peptides that are presented on human leucocyte antigen (HLA)-DR. In the present work, we compared the repertoire of FVIII-derived peptide presented on HLA-DR and HLA-DQ. Monocyte-derived dendritic cells from 9 HLA-typed healthy donors were pulsed with recombinant factor VIII. HLA-DR and HLA-DQ molecules were purified using monoclonal antibodies. Our data show that HLA-DQ and HLA-DR present a similar repertoire of factor VIII-derived peptides. However, the number of peptides associated with HLA-DQ was lower when compared to HLA-DR. We also identified a peptide, within the acidic a3 domains of factor VIII that is presented with higher frequency on HLA-DQ. Interestingly, this peptide was found to have a higher predicted affinity for HLA-DQ when compared to HLA-DR. Taken together, our data suggest that HLA-DQ participates in the presentation of factor VIII peptides, thereby contributing to the development of inhibitory antibodies in a proportion of patients with severe hemophilia A. Copyright © 2017, Ferrata Storti Foundation.

  20. Development of Integrated Natural Science Teaching Materials Webbed Type with Applying Discourse Analysis on Students Grade VIII in Physics Class

    Science.gov (United States)

    Sukariasih, Luh

    2017-05-01

    This study aims to produce teaching materials integrated natural science (IPA) webbed type of handout types are eligible for use in integrated science teaching. This type of research IS a kind of research and development / Research and Development (R & D) with reference to the 4D development model that is (define, design, develop, and disseminate). Data analysis techniques used to process data from the results of the assessment by the validator expert, and the results of the assessment by teachers and learners while testing is limited (12 students of class VIII SMPN 10 Kendari) using quantitative descriptive data analysis techniques disclosed in the distribution of scores on the scale of five categories grading scale that has been determined. The results of due diligence material gain votes validator material in the category of “very good” and “good”, of the data generated in the feasibility test presentation obtained the category of “good” and “excellent”, from the data generated in the feasibility of graphic test obtained the category of “very good “and” good “, as well as of the data generated in the test the feasibility of using words and language obtained the category of“very good “and” good “, so with qualifications gained the teaching materials IPA integrated type webbed by applying discourse analysis on the theme of energy and food for Junior High School (SMP) grade VIII suitable as teaching materials. In limited testing, data generated in response to a science teacher at SMPN 10 Kendari to product instructional materials as “excellent”, and from the data generated while testing is limited by the 12 students of class VIII SMPN 10 Kendari are more students who score indicates category “very good”, so that the qualification obtained by the natural science (IPA) teaching material integrated type webbed by applying discourse analysis on the theme of energy and food for SMP / class VIII fit for use as teaching material.

  1. Pengembangan Materi Luas Permukaan Dan Volum Limas Yang Sesuai Dengan Karakteristik Pmri Di Kelas VIII SMP Negeri 4 Palembang

    OpenAIRE

    Hariyati, Hariyati; Indaryanti, Indaryanti; Zulkardi, Zulkardi

    2008-01-01

    Penelitian ini bertujuan mengembangkan materi luas permukaan dan volum limas dengan pendekatan PMRI. Subjek dalam penelitian ini adalah siswa kelas VIII SMP Negeri 4 Palembang. Dalam mengembangkan materi terdapat proses evaluasi formatif dan uji coba terhadap materi, yaitu expert review, one-to-one evaluation, small group, dan field test. Dari tiga tahap pertama, materi dinyatakan valid. Kemudian materi diujicobakan di lapangan (field test). Dari hasil uji coba diperoleh simpulan yaitu mengha...

  2. PENGARUH VIRTUAL LABORATORY BERBASIS FLASH ANIMATION TERHADAP PEMAHAMAN KONSEP DAN KETERAMPILAN BERPIKIR KRITIS PESERTA DIDIK TEMA OPTIK KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Nuzul Andri Permana

    2017-02-01

    ___________________________________________________________________ Availability of practical tools in learning of science subject is needed to achieve the learning objectives. Based on observations in Junior High School 10 Semarang, practicum low intensity because of practical tools ara not available that support learning activities. The intensity of practicum is low, it make critical thinking skills of students is low. Critical thinking skills to be one of the variables that influence of understanding concept of learners. Availability of practicum tools that incomplete requires teachers to achieve the learning objectives by using media that can support learners to be able to do practicum virtually. Media that can support to do practicum virtually is a virtual laboratory. This study aims to determine the influence of virtual laboratory based flash animation againts understanding concepts and critical thinking skills of students in grade VIII SMP in optical theme. The population used in this study were all students of grade VIII Junior High School 10 Semarang academic year 2015/2016. Sampling technique used is purposive sampling and obtained VIII C as the experimental class and VIII F as the control class. The design of study is nonequivalent control group design. The results showed that the correlation value of understanding concept of students is 0.660 which shows in the strong category and correlation analysis of students' critical thinking skills of 0,729 based on observational data and 0.69 based on the posttest data that shows in the strong category. The influence of the use of virtual laboratory-based flash animation againts understanding concept of students is 43.53%, whereas the influence the use of virtual laboratory based flash animation againts the critical thinking skills of students is 53.14% based on observational data and 47.06% based on the posttest data. The conclusion is there are infuence of virtual laboratory based flash animation againts

  3. Neurotology findings in patients with diagnosis of vascular loop of cranial nerves VIII in magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Grocoske, Francisco Luiz Busato

    Full Text Available Introduction: The vascular compression by redundant vessels under the VIII cranial nerves has been studied since the 80's, and many authors proposed correlations between the compression and the otoneurological findings (vertigo, tinnitus, hypoacusis, audiometry and electrophysiological findings. Objective: Analyze and correlate the different signs and otoneurological symptoms, the audiological findings and its incidence over individuals with Vascular Loop (VL diagnosis of VIII cranial nerves by magnetic resonance imaging (MRI. Method: Retrospective study through the analysis of medical records of 47 patients attended in the otoneurology clinic of Clinical Hospital of UFPR. All the patients have MRI exams with compatible pictures of VL of the VIII cranial nerves. Results: The tinnitus was the most frequent symptom, in 83% of the patients, followed by hypoacusis (60% and vertigo (36%. The audiometry presented alterations in 89%, the brainstem evoked auditory potential in 33% and the vecto-electronystagmography in 17% of the patients. Was not found statistically significant relation between the buzz or hypoacusis, and the presence of VL in MRI. Only 36% of patients had complaints of vertigo, the main symptom described in theory of vascular compression of the VIII pair of nerve. As in the audiometry and in brainstem evoked auditory potential was not found a statistically significant relation between the exam and the presence of the VL in the RMI. Conclusion: The results show independence between the findings of the RMI, clinical picture and audiological results (p>0,05 suggesting that there are no exclusive and direct relation between the diagnosis of vascular loop in the MRI and the clinical picture matching.

  4. Pengaruh Model Pembelajaran Berbasis Masalah terhadap Prestasi Belajar Matematika dan Keterampilan Berpikir Kritis Siswa Kelas VIII SMP Negeri 2 Abang

    OpenAIRE

    KD ARYA UTAMA JAYA; PROF.DR. NASWAN SUHARSONO, M.Pd; DRA. NI NYOMAN PARWATI, M.Pd

    2015-01-01

    Tujuan penelitian ini adalah untuk mendeskripsikan perbedaan prestasi belajar matematika dan keterampilan berpikir kritis antara siswa yang belajar dengan menerapkan model pembelajaran berbasis masalah dan siswa yang belajar dengan menerapkan model pembelajaran konvensional. Penelitian ini merupakan penelitian quasi experiment dengan pretest-posttest non-equivalent control group design. Sampel penelitian adalah dua kelas VIII di SMP Negeri 2 Abang tahun pelajaran 2015/2016 yang ditentukan den...

  5. MX Siting Investigation. Geotechnical Evaluation. Volume VIII. Nevada - Utah Verification Studies, FY 79. Geotechnical Data Big Smoky CDP, Nevada.

    Science.gov (United States)

    1979-08-24

    Angular - particles have sharp edges and relatively plane sides with unpolished surfaces. wfl . AT#UNL, EWE. FN-TR-27-VIII 6-5 Subangular - particles... GEM ~GIC UNIT My ’All .’j GP T-3 C-33 St FACE ELEV TION: 492j * 1500m) SM jSIRFICIAL GE LOGIC UNIT: AMy A3 SW-SM F -6 C-34 SURFACE ELEVATION: 4938

  6. Identification of a mutant locus that bypasses the BsgA protease requirement for social development in Myxococcus xanthus.

    Science.gov (United States)

    Cusick, John K; Hager, Elizabeth; Gill, Ronald E

    2015-01-01

    The BsgA protease is required for the earliest morphological changes observed in Myxococcus xanthus development. We hypothesize that the BsgA protease is required to cleave an inhibitor of the developmental program, and isolation of genetic bypass suppressors of a bsgA mutant was used to identify signaling components controlling development downstream of the BsgA protease. Strain M955 was created by transposon mutagenesis of a bsgA mutant followed by screening for strains that could develop despite the absence of the BsgA protease. Strain M955 was able to aggregate, form fruiting bodies, and partially restored the production of viable spores in comparison to the parental bsgA mutant. The bsgA Tn5Ω955 strain partially restored developmental expression to a subset of genes normally induced during development, and expressed one developmentally induced fusion at higher amounts during vegetative growth in comparison to wild-type cells. The transposon in strain M955 was localized to a Ribonuclease D homolog that appears to exist in an operon with a downstream aminopeptidase-encoding gene. The identification of a third distinct bypass suppressor of the BsgA protease suggests that the BsgA protease may regulate a potentially complex pathway during the initiation of the M. xanthus developmental program. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. EARLY POSTOPERATIVE COMPLICATIONS IN ROUX-EN-Y GASTRIC BYPASS.

    Science.gov (United States)

    Stoll, Aluisio; Rosin, Leandro; Dias, Mariana Fernandes; Marquiotti, Bruna; Gugelmin, Giovana; Stoll, Gabriela Fanezzi

    Roux-en-Y gastric bypass is one of the most common bariatric surgery and leads to considerable weight loss in the first months. To quantify the main early postoperative complications in patients submitted to the gastric bypass. Observational retrospective cohort. Data of 1051 patients with class II obesity associated with comorbidities or class III obesity submitted to the gastric bypass with 30 days of follow-up starting from the date of the surgery. The age average was 36 years with a predominance of females (81.1%). The mean preoperative body mass index was 43 kg/m². The major complication was fistula (2.3%), followed by intestinal obstruction (0.5%) and pulmonary embolism (0.5%). Death occurred in 0.6% of the cases. In the period of 30 days after surgery the overall complication rate was 3.8%; reoperation was necessary in 2.6% and death occurred in 0.6%. Fistula was the main complication and the leading cause of hospitalization in intensive care unit, reoperation and death. Bypass gástrico em Y-de-Roux é uma das operações bariátricas mais comuns e leva a perdas consideráveis de peso já nos primeiros meses. Quantificar as principais complicações pós-operatórias precoces em pacientes submetidos ao bypass gástrico. Coorte retrospectiva observacional. Amostra de 1051 pacientes portadores de obesidade grau II associada à comorbidades ou grau III submetidos ao bypass gástrico com acompanhamento de 30 dias a partir da data da operação. A idade média dos pacientes foi de 36 anos com predominância de mulheres (81,1%). O índice de massa corporal pré-operatório médio foi de 43 kg/m². A principal complicação foi fístula (2,3%), seguida de obstrução intestinal (0,5%) e tromboembolismo pulmonar (0,5%). Óbito ocorreu em 0,6% dos casos. No período de 30 dias de pós-operatório a taxa geral de complicações foi de 3,8%; a de reoperação de 2,6% e óbito em 0,6%. A fístula foi a principal complicação e a principal causa de internamento em

  8. Total laparoscopic bypass for aortoiliac occlusive lesions: 93-case experience.

    Science.gov (United States)

    Coggia, Marc; Javerliat, Isabelle; Di Centa, Isabelle; Colacchio, Giovanni; Leschi, Jean Pascal; Kitzis, Michel; Goëau-Brissonnière, Olivier A

    2004-11-01

    We describe our experience with a new technique of total laparoscopic bypass surgery to treat aortoiliac occlusive lesions. From November 2000 to December 2003, 93 total laparoscopic bypass procedures were performed to treat TASC (TransAtlantic Inter-Society Consensus document) grade C or D aortoiliac occlusive lesions. We also reimplanted 2 inferior mesenteric arteries, and performed 3 prosthesis-superior mesenteric bypasses and 2 suprarenal aorta endarterectomies. Our technique includes a sloping right lateral decubitus installation, which enables a simple transperitoneal left retrocolic or retrorenal approach to the infrarenal abdominal aorta. In patients with a hostile abdomen a retroperitoneal videoscopic approach was used. Aorta-prosthesis laparoscopic anastomoses are performed simply, which averts any trauma to the suture material. Patients included 76 men and 17 women, with median patient age 61 years (range, 38-79 years). The approach to the aorta was always possible, in particular, in obese patients. It enabled stable aortic exposure during performance of the laparoscopic aorta-prosthesis anastomosis. Median operative time was 240 minutes (range, 150-450 minutes). Median aortic clamping time measured to unclamping of the first prosthetic limb was 67.5 minutes (range, 30-135 minutes). Median duration of aorta-prosthesis anastomosis was 30 minutes (range, 12-90 minutes). The longest durations were mainly observed during the learning curve. Thirty-day postoperative mortality was 4% (4 of 93 patients). Two patients died of myocardial infarction. One patient with American Society of Anesthesiologists grade 4 disease operated on to treat critical ischemia died of multiple organ system failure, and 1 patient died of colonic ischemia. Major nonlethal postoperative complications were observed in 4 patients, and included lung atelectasia in 2 patients, graft infection in 1 patient operated on emergently to treat aortic occlusion, and secondary spleen rupture at day

  9. MENINGKATKAN PEMBELAJARAN HOCKEY MELALUI PERMAINAN 4 GAWANG KECIL PADA SISWA KELAS VIII 3 SMP MUHAMMADIYAH 4 SEMARANG TAHUN 2015

    Directory of Open Access Journals (Sweden)

    Muhammad Taufiq

    2016-02-01

    Full Text Available The purpose of this result the study learning of hockey games through the 4 Small Wicket Game in Grade VIII 3 students of Smp Muhammadiyah 4 Semarang. In this case the right is 4 semarang. research method. In practice consists of two cycles. Based on the results of the research, it showed the percentage of passing students study result in the first cycle, students who got pass score are 58.33% (21 students and who did not pass are 41.66% (15 students. In the second cycle students who got pass score are 88.88% (34 students and students who did not pass are 11.11% (4 students. It indicates an increase completeness of student study result is 30.55%.Based on the research’s result, it can be concluded that the use of 4 Small Wicket Game in Grade VIII 3 students is right to improve the study result of grade VIII 3 students of SMP Muhammadiyah 4 Semarang in learning hockey.

  10. Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.; Antonarakis, S.E. [Univ. of Geneva (Switzerland); Inaba, Hiroshi [Tokyo Medical College (Japan)] [and others

    1997-03-01

    Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.

  11. Indoleamine 2,3-dioxygenase attenuates inhibitor development in gene-therapy-treated hemophilia A mice.

    Science.gov (United States)

    Liu, L; Liu, H; Mah, C; Fletcher, B S

    2009-06-01

    A serious impediment to gene and protein replacement therapy in hemophilia A is the development of inhibitors. Mechanisms responsible for inhibitor development include T-cell-dependent adaptive immune responses and the CD28-B7 signaling pathway that eventually leads to the formation of antibodies directed against factor VIII (FVIII). Indoleamine 2,3-dioxygenase (IDO) is a potent immunosuppressive enzyme that can inhibit T-cell responses and induce T-cell apoptosis by regulation of tryptophan metabolism. Kynurenine, one of the metabolites of tryptophan, has been implicated as an immune modulator. Here we hypothesize that co-delivery of the genes for FVIII and IDO can attenuate inhibitor formation. Using transposon-based gene delivery, we observed long-term therapeutic FVIII expression and significantly reduced inhibitor titers when the genes were co-delivered. Co-expression of FVIII and IDO in the liver was associated with increased plasma kynurenine levels, an inhibition of T-cell infiltration and increased apoptosis of T cells within the liver. These experiments suggest that modulation of tryptophan catabolism through IDO expression provides a novel strategy to reduce inhibitor development in hemophilia gene/protein therapy.

  12. Functional mapping of the A2 domain from human factor VIII.

    Science.gov (United States)

    Plantier, Jean-Luc; Saboulard, Didier; Pellequer, Jean-Luc; Négrier, Claude; Delcourt, Marc

    2012-02-01

    Coagulation factor VIII (FVIII) is a multidomain glycoprotein in which the FVIII A2 domain is a key structural element. We aimed at identifying residues within FVIII A2 domain that are crucial for the maintenance of the cofactor function. A high number (n=206) of mutants were generated by substituting original residues with alanine. The mutants were expressed in COS-1 cells and their antigen levels and procoagulant activities were measured. The residues were classified in three categories: those with a non-detrimental alteration of their activities (activity >50 % of control FVIII; n=98), those with a moderate alteration (15 %maintenance of the A2 domain structure. In contrast, residues resistant to mutations formed external loops without well- defined structures suggesting that these loops were not crucial for the process of factor X activation. This study provided a detailed map of the FVIII A2 domain between residues 371 and 649, identifying residues crucial for maintaining FVIII function and residues that can be mutated without jeopardising the coagulant activity.

  13. Characteristics of rabbit transgenic mammary gland expressing recombinant human factor VIII.

    Science.gov (United States)

    Chrenek, P; Makarevich, A V; Pivko, J; Massanyi, P; Lukac, N

    2009-02-01

    The objective of this research was to compare (i) the content of milk protein and recombinant human factor VIII (rhFVIII) in the milk of transgenic and non-transgenic rabbit females at three lactations and (ii) histological structure, ultrastructural morphology and occurrence of apoptosis in rabbit transgenic and non-transgenic mammary gland during third lactation and involution. Significant differences (t(0.05)) in milk protein content were found between transgenic and non-transgenic at all three lactations. The percentage of apoptotic cells was significantly higher (t(0.01)) in non-transgenic ones compared with transgenic mammary gland tissues (6.5% versus 2.4%) taken at the involution stage. Morphometrical analysis of histological preparations at the involution stage detected a significantly higher (t(0.05)) relative volume of lumen in transgenic animals compared with non-transgenic ones (60.00 versus 46.51%). Ultrastructural morphology of the transgenic mammary gland epithelium at the involution stage revealed an increased relative volume of protein globules (t(0.05)); at the lactation stage, a significantly higher volume of mitochondria (13.8%) compared with the non-transgenic (9.8%) ones was observed. These results, although revealing differences in some parameters of ultrastructure and histology, indicate no harmful effect of the mouse whey acid protein-hFVIII transgene expression on the state of mammary gland of transgenic rabbit females.

  14. [Organoleptic and physicochemical characteristics of propolis in the Province Of Nuble, VIII Region-Chile].

    Science.gov (United States)

    Hernández, M S; Lazo, C S; Junod, J M; Arancibia, J M; Flores, R S; Valencia, A E; Valenzuela, E V

    2005-12-01

    Propolis ("bee-glue") is a gummy resinous substance elaborated by honey bees (Apis mellifera) from different types of plant resins. The chemical composition of propolis is very complex and variable as it depends on the botanical source and the environmental conditions prevailing at the location where the resin is collected by bees. The objective [corrected] of this study was to determine the propolis organoleptic and physicochemical properties of different types in the Province of Nuble (VIII Región, Chile). Samples were collected at different sites located in the Central Valley, ranging from the coast to the mountain skirts. Analyses included humidity, ashes, wax content, total phenolics content, total flavonoids, mechanical impurities, oxidation time, and solubility in ethanol. Results showed that propolis extracts from coastal sites are better quality than those collected at mountain skirts, and these in turn are better than propolis obtained from the Central Valley. All propolis analyzed in this study can be classified according to the Brazilian norm as high flavonoid content. The same homogeneity is observed in the amounts of total phenolics found in the samples. In general terms, properties of the propolis samples analyzed fulfill the quality requirements of the current international standards.

  15. IMPROVING WRITING DESCRIPTIVE TEXT BY USING NLP STRATEGY AT VIII GRADE OF SMPN 11 DURI

    Directory of Open Access Journals (Sweden)

    Dahler Dahler

    2017-07-01

    Full Text Available This research is based on the problem faced by the students such as: difficulty inunderstanding the generic structures of descriptive text and the difficulties in developingparagraph. The purpose of this research was to improve the students’ writing skill by usingNeuro Linguistics Programming (NLP strategy at VIII grade of SMPN 11 Mandau Duri. Theresearch design was Classroom Action Research (CAR consisted of two cycles. The datawere collected by using test, field note, observation sheet, and interview. Then, the datacollected were analyzed by using scoring rubric of writing descriptive text. The result showedthat students’ ability in writing descriptive text could be improved. It could be seen frombased score of students writing skill was 38 (failed improve to 51 (failed in cycle 1 to 70(Pass in cycle II. It was caused by some factors, those were the teacher gave motivation,created enjoyfull experience, comfortable class and used various media. In conclusion, theuse of NLP strategy has many beneficial.Keywords:Writing skill, Descriptive Text and NLP strategy.

  16. [Determinants of the elevated factor VIII activity in patients following venous thromboembolism].

    Science.gov (United States)

    Lech, Monika; Kościelniak, Barbara; Bryk, Agata; Undas, Anetta

    2016-01-01

    Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p 200% (p = 0.016). The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.

  17. PENGGUNAAN MIND MAP DIIRINGI MUSIK KLASIK DALAM PEMBELAJARAN MATEMATIKA UNTUK SISWA KELAS VIII SMPN 1 SAWAHLUNTO

    Directory of Open Access Journals (Sweden)

    Rezky Ramadhona

    2016-06-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui apakah motivasi dan hasil belajar belajar matematika siswa kelas VIII SMPN 1 Sawahlunto setelah menggunakan mind map dan musik klasik lebih baik dari sebelum menggunakan mind map dan musik klasik. Jenis penelitian ini adalah penelitian eksperimen dengan menggunakan dua model rancangan yaitu One Group Pretest Posttest Design untuk melihat dampak perlakuan terhadap motivasi belajar dan Randomized Control Group Only Design untuk melihat dampak perlakuan terhadap hasil belajar. Pengumpulan data dalam penelitian ini menggunakan angket dan tes akhir berupa soal essai. Data yang diperoleh dianalisis dengan menggunakan Uji-t. Hasil penelitian menunjukkan bahwa motivasi belajar matematika siswa cenderung meningkat. Jadi disimpulkan bahwa motivasi belajar matematika siswa setelah menggunakan mind map dan musik klasik lebih baik dari pada sebelum menggunakan mind map dan musik klasik. Dari hasil uji hipotesis untuk data hasil belajar pada selang kepercayaan α = 0,05 diperoleh P-value = 0,022. Jadi dapat disimpulkan bahwa hasil belajar matematika siswa yang menggunakan mind map dan musik klasik lebih baik dari hasil belajar matematika siswa yang tidak menggunakan mind map dan musik klasik. Kata Kunci: Mind Map, Musik Klasik DOI: http://dx.doi.org/10.22342/jpm.10.2.3636.87-92

  18. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner

    2011-01-01

    of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V......In vivo, clotting Factor VIII (FVIII) circulates in plasma bound to von Willebrand factor (vWF), and the vWF:FVIII complex prevents binding of FVIII to phosphatidylserine (PS). Activation of FVIII by thrombin releases FVIII from vWF, and subsequently FVIII binds to PS exposed on activated platelets...... of the production cells. Recently, we showed that as much as 90% of secreted rFVIII is bound to transiently transfected production cells during serum free conditions. In this study, we investigated the effect of including vWF in the serum free medium, and demonstrate that addition of vWF results in release...

  19. Lithium ionophore VIII as an extraordinarily effective receptor for the strontium cation: Experimental and theoretical study

    Science.gov (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr; Bouř, Petr

    2014-03-01

    From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Sr2+(aq) + 2A-(aq) + 1(nb) ⇔ 1ṡSr2+(nb) + 2A-(nb) taking place in the two-phase water-nitrobenzene system (A- = picrate, 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log Kex (1ṡSr2+, 2A-) = 7.8 ± 0.1. Further, the extremely high stability constant of the 1ṡSr2+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log βnb (1ṡSr2+) = 16.9 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1ṡSr2+ was derived. In the resulting complex, the "central" cation Sr2+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1; the interaction energy of this complex was found to be -959.9 kJ/mol.

  20. Lithium ionophore VIII as an extraordinarily strong receptor for the trivalent europium cation

    Science.gov (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr

    2015-01-01

    On the basis of extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Eu3+(aq) + 3A-(aq) + 1(nb) ⇆ 1.Eu3+(nb) + 3A-(nb) occurring in the two-phase water-nitrobenzene system (A- = CF3SO-3; 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was determined as log Kex (1.Eu3+, 3A-) = 2.5 ± 0.1. Furthermore, the extremely high stability constant of the 1.Eu3+ complex in nitrobenzene saturated with water was calculated: log βnb (1.Eu3+) = 15.6 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1.Eu3+ was derived. In the resulting complex, the 'central' cation Eu3+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1. It is evident that this exceptionally effective receptor 1 for the Eu3+ cation could be considered as a potential extraction agent for nuclear waste treatment.