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

The new albumin-free recombinant factor VIII concentrates for treatment of hemophilia: do they represent an actual incremental improvement?

Science.gov (United States)

Josephson, Cassandra D; Abshire, Thomas

2004-07-01

The goal of eliminating the low levels of infectious disease risk from hemophilia treatment has resulted in the development of multiple generations of recombinant factor VIII (rFVIII) products. The ideal product should be devoid of human and animal proteins, which may transmit infectious agents. These products should also maintain molecular integrity, hemostatic efficacy, similar immunogenicity, and acceptable side effect profiles as compared to plasma-derived factor VIII. Currently available first-, second-, and third-generation rFVIII products include Recombinate; Kogenate FS/Helixate FS and ReFacto; and Advate, respectively. During the evolution of rFVIII products, either full-length or B-domain-deleted factor VIII were transfected into immortalized cell lines. The B-domain-deleted product, ReFacto, has resulted in an additional method to monitor factor VIII levels. The third-generation products offer the theoretical advantage of being produced without human and/or animal proteins. Upon initial introduction into the marketplace, the newer products have a higher cost. However, when analyzing historical trends, the prices of these products are almost equivalent to first-generation products within 3 years of licensure. Thus, the initial cost of the product may be a minimal issue in the medical decision process when selecting rFVIII replacement therapy.

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

Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor VIII.

Science.gov (United States)

El Adib, Ahmed Ghassan; Majdi, Farah; Dilai, Mohamed Othmane; Asmouki, Hamid; Bassir, Ahlam; Harou, Karam; Soumani, Abderraouf; Younous, Said; Mahmal, Lahoucine

2014-01-01

Inherited combined factor V and factor VIII deficiency (F5F8D) is autosomal recessive transmission disorder. Epistaxis, postsurgical bleeding, and menorrhagia are the most common symptoms. The risk of miscarriage and placental abruption is consequent. We report a case of successful pregnancy in a patient with F5F8D. 20-year-old woman, born of consanguineous parents, third gestate, first parity, two miscarriages, admitted for child birth of a spontaneous pregnancy estimated at 38 weeks and was diagnosed with F5F8D. At admission, patient was hemodynamically stable, with good obstetric conditions. The biologic results showed low levels of PT (52%), factor V (7%), and factor VIII (5%), and the activated partial thromboplastin time was prolonged (68,6%). Parturient was admitted in intensive care unit, maternal and fetal monitoring was performed. Fresh frozen plasma (FFP) and factor VIII concentrates were perfused at the induction of labor. Analgesia used fentanyl titration. The delivery gave birth to a newborn male, with Apgar 10/10 and 3000 g. The puerperium was simple without any important bleeding. Laboratory tests for the newborn were acceptable. Little literature is available on this subject and there are no guidelines available concerning pregnancy; we chose to prescribe a combination of factor VIII concentrate and FFP in pre-, per- and postpartum. The same protocol was successfully used in a patient before dental extraction and prostatectomy. Vaginal delivery is possible, as our case. Management by multidisciplinary team is recommended.

Acquired high titre factor VIII inhibitor with underlying polyarteritis nodosa.

Science.gov (United States)

Snowden, J A; Hutchings, M; Spearing, R; Patton, W N

1997-05-01

We here present the case of a 70-year-old woman referred to our unit for investigation of bleeding. Investigations confirmed a high titre acquired Factor VIII inhibitor. In association there was relapse of systemic illness associated with anti-neutrophil cytoplasmic antibodies (atypical pattern) for which she had been treated five years previously. Immunosuppression was attempted, but it failed to have an impact both on the inhibitor titre and on the underlying disorder. The patient died from multi-organ failure and massive chest hemorrhage. Post-mortem showed necrotizing vasculitis of medium sized vessels at several sites, including the kidney, consistent with a diagnosis of polyarteritis nodosa. Although it is well recognised that Factor VIII inhibitors are found in conjunction with autoimmune disorders, this case is significant in that it is the first associated with histologically proven polyarteritis nodosa type vasculitis. The case illustrates the difficulties in the investigation and management of patients with acquired high titre Factor VIII inhibitors.

Chromogenic Factor VIII Assays for Improved Diagnosis of Hemophilia A.

Science.gov (United States)

Rodgers, Susan; Duncan, Elizabeth

2017-01-01

Hemophilia A is an inherited bleeding disorder caused by a reduced level of factor VIII coagulant activity (FVIII:C) in blood. Bleeding episodes may occur spontaneously in the severe form of hemophilia or after trauma in the milder forms. It is important that patients are diagnosed correctly, which includes placing them into the correct severity category of the disorder so that appropriate treatment can be given. Diagnosis is made by determination of the amount of FVIII:C in the blood, usually using a one-stage factor VIII:C assay. However, approximately one third of patients with mild or moderate hemophilia will have much lower results by the chromogenic assay, with some of them having normal results by the one-stage assay. The chromogenic factor VIII assay is used in some specialized hemophilia reference centers and is recommended for the diagnosis of mild hemophilia A, as this assay is considered to better reflect the severity status of hemophilia patients than the one-stage assay.

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

OpenAIRE

Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Nichols, Timothy C.; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by fu...

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.

Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine.

Science.gov (United States)

Gilbert, G E; Drinkwater, D

1993-09-21

Phosphatidylserine, a negatively charged lipid, is exposed on the platelet membrane following cell stimulation, correlating with the expression of factor VIII receptors. We have explored the importance of the negative electrostatic potential of phosphatidylserine vs chemical moieties of phosphatidylserine for specific membrane binding of factor VIII. Fluorescein-labeled factor VIII bound to membranes containing 15% phosphatidic acid, a negatively charged phospholipid, with low affinity compared to phosphatidylserine-containing membranes. Binding was not specific as it was inhibited by other proteins in plasma. Factor VIII bound to membranes containing 10% phosphatidylserine in spite of a varying net charge provided by 0-15% stearylamine, a positively charged lipid. The soluble phosphatidylserine moiety, O-phospho-L-serine, inhibited factor VIII binding to phosphatidylserine-containing membranes with a Ki of 20 mM, but the stereoisomer, O-phospho-D-serine, was 5-fold less effective. Furthermore, binding of factor VIII to membranes containing synthetic phosphatidyl-D-serine was 5-fold less than binding to membranes containing phosphatidyl-L-serine. Membranes containing synthetic phosphatidyl-L-homoserine, differing from phosphatidylserine by a single methylene, supported high-affinity binding, but it was not specific as factor VIII was displaced by other plasma proteins. O-Phospho-L-serine also inhibited the binding of factor VIII to platelet-derived microparticles with a Ki of 20 mM, and the stereoisomer was 4-fold less effective. These results indicate that membrane binding of factor VIII is mediated by a stereoselective recognition O-phospho-L-serine of phosphatidylserine and that negative electrostatic potential is of lesser importance.

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.

Characterization of five partial deletions of the factor VIII gene

International Nuclear Information System (INIS)

Youssoufian, H.; Antonarakis, S.E.; Aronis, S.; Tsiftis, G.; Phillips, D.G.; Kazazian, H.H. Jr.

1987-01-01

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, the authors have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes

Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

Science.gov (United States)

Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

2017-06-01

Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia a

NARCIS (Netherlands)

C.L. Eckhardt (Corien); A.S. van Velzen (Alice); M.A.D. Peters (Marjolein); J. Astermark (Jan); P.P. Brons; G. Castaman (Giancarlo); M.H. Cnossen (Marjon); N. Dors (N.); C. Escuriola-Ettingshausen (Carmen); K. Hamulyák (K.); D.P. Hart (Daniel); C.R.M. Hay (Charles R.); S. Haya (Saturnino); W.L. van Heerde; C. Hermans (Cédric); M. Holmström (Margareta); V. Jimenez-Yuste (Victor); R.D. Keenan (Russell); R. Klamroth (Robert); B.A.P. Laros-Van Gorkom (Britta); F.W.G. Leebeek (Frank); R. Liesner (Ri); A. Mäkipernaa (Anne); C. Male (Christoph); E.P. Mauser-Bunschoten (Eveline); M.G. Mazzucconi (Maria); S. McRae (Simon); K. Meijer (K.); M. Mitchell (Michael); M. Morfini (Massimo); M.R. Nijziel (Marten); J. Oldenburg (Jan); K. Peerlinck; P. Petrini (Pia); H. Platokouki (Helena); S.E. Reitter-Pfoertner (Sylvia); E. Santagostino (Elena); P. Schinco (Piercarla); F.J.W. Smiers (Frans); K.D. Siegmund (Kimberly); A. Tagliaferri (Annarita); T.T. Yee (Thynn); P.W. Kamphuisen (Pieter Willem); J.G. van der Bom (Anske); K. Fijnvandraat

2013-01-01

textabstractNeutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into

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.

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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.

Factor VIII-associated antigen in human lymphatic endothelium.

Science.gov (United States)

Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

1987-03-01

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A.

Science.gov (United States)

O'Brien, D P; Tuddenham, E G

1989-06-01

We have purified the factor VIII from a CRM+ Hemophilia A plasma (90 U/dL VIII:Ag but 0 U/dL VIII:C) and analyzed the protein before and after thrombin activation by Western blotting with monoclonal antibodies (MoAbs). Normal or patient citrated plasma was ultracentrifuged, cryo-ethanol-precipitated and chromatographed on Sepharose 6B. The void volume fractions were reduced and subjected to ion exchange chromatography yielding material of specific activity approximately 1,000 U/mg protein (VIII:C or VIII:Ag). Factor VIII purified in this way from normal plasma is fully activatable by thrombin with proteolytic fragmentation as previously described by F. Rotblat et al (Biochemistry 24: 4294, 1985). Factor VIII 1,689-Cys has the normal distribution of factor VIII light and heavy chains prior to thrombin activation. After exposure to thrombin the heavy chain polypeptides were fully proteolysed but the light chain was totally resistant to cleavage. This is consistent with the demonstration in the patient's leucocyte DNA of a C to T transition in codon 1,689 converting Arg to Cys at the light chain thrombin cleavage site as previously described by J. Gitschier et al (Blood 72:1022, 1988). Uncleaved light chain of Factor VIII 1,689-Cys is not released from von Willebrand factor (vWF) by thrombin, but this is not the sole cause of the functional defect since the protein purified free of vWF has no coagulant activity. We conclude that the functional defect in factor VIII 1,689-Cys is a consequence of failure to release the acidic peptide from the light chain upon thrombin activation.

Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

International Nuclear Information System (INIS)

Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

1990-01-01

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

Science.gov (United States)

Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

2005-01-01

Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

Recurrent myocardial infarctions in a young football player secondary to thrombophilia, associated with elevated factor VIII activity

Directory of Open Access Journals (Sweden)

Vacek TP

2014-10-01

Full Text Available Thomas P Vacek, Shipeng Yu, Shahnaz Rehman, Blair P Grubb, Daniel Kosinski, Cherian Verghese, Ehab A Eltahawy, Shafiq Qaiser Department of Medicine, University of Toledo Medical Center, Toledo, OH, USAAbstract: Myocardial infarction (MI due to coronary atherosclerosis in young adults is uncommon; rare causes such as cocaine abuse, arterial dissection, and thromboembolism should be considered. A 21-year-old football player, and otherwise healthy African American man, developed chest pain during exercise while bench-pressing 400 lbs. Acute MI was diagnosed based on physical examination, electrocardiography findings, and elevated cardiac enzymes. Coronary arteriography showed a thrombus occluding the proximal left anterior descending artery (LAD. Aggressive antiplatelet therapy with aspirin, clopidogrel, and eptifibatide was pursued, in addition to standard post-MI care. This led to the successful resolution of symptoms and dissolution of the thrombus, demonstrated by repeat coronary arteriography. Five months later, he presented with similar symptoms during exercise after lifting heavy weights, and was found to have another acute MI. Coronary arteriography again showed a thrombus occluding the LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild atherosclerotic plaque burden was observed on both occasions by intravascular ultrasound. A bare metal stent was placed at the site as it was thought this site had acted as a nidus for small plaque rupture and thrombus formation. Elevated serum factor VIII activity at 205% (reference range 60%–140% was found, a rare cause of hypercoagulability. Further workup revealed a patent foramen ovale during a Valsalva maneuver by transesophageal echocardiography. Both events occurred during weight lifting, which can transiently increase right heart pressure in a similar way to the Valsalva maneuver. In light of all the findings, we concluded that an exercise-related increase in factor

The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models.

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Abimbola A Onasoga-Jarvis

Full Text Available Clinical evidence suggests that individuals with factor VIII (FVIII deficiency (hemophilia A are protected against venous thrombosis, but treatment with recombinant proteins can increase their risk for thrombosis. In this study we examined the dynamics of thrombus formation in individuals with hemophilia A and their response to replacement and bypass therapies under venous flow conditions. Fibrin and platelet accumulation were measured in microfluidic flow assays on a TF-rich surface at a shear rate of 100 s⁻¹. Thrombin generation was calculated with a computational spatial-temporal model of thrombus formation. Mild FVIII deficiencies (5-30% normal levels could support fibrin fiber formation, while severe (1 nM, but too low to support fibrin formation (<10 nM. In the absence of platelets, fibrin formation was not supported even at normal FVIII levels, suggesting platelet adhesion is necessary for fibrin formation. Individuals treated by replacement therapy, recombinant FVIII, showed normalized fibrin formation. Individuals treated with bypass therapy, recombinant FVIIa, had a reduced lag time in fibrin formation, as well as elevated fibrin accumulation compared to healthy controls. Treatment of rFVIIa, but not rFVIII, resulted in significant changes in fibrin dynamics that could lead to a prothrombotic state.

Progress toward inducing immunologic tolerance to factor VIII

OpenAIRE

Scott, David W.; Pratt, Kathleen P.; Miao, Carol H.

2013-01-01

A major problem in treating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies. These antibodies block (inhibit) the procoagulant function of FVIII and thus are termed “inhibitors.” The currently accepted clinical method to attempt to eliminate inhibitors is immune tolerance induction (ITI) via a protocol requiring intensive FVIII treatment until inhibitor titers drop. Although often successful, ITI is ext...

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

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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

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

NARCIS (Netherlands)

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

Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.

Science.gov (United States)

Arai, M; Higuchi, M; Antonarakis, S E; Kazazian, H H; Phillips, J A; Janco, R L; Hoyer, L W

1990-01-15

The molecular defect responsible for moderate and severe hemophilia A has been identified for two unrelated patients with the CRM-positive form of this disorder (factor VIII activity of 0.02 and 0.05 U/mL with factor VIII antigen of 0.87 and 2.20 U/mL). In both cases, the immunopurified dysfunctional factor VIII protein is abnormal, in that the 80 Kd light chain is not cleaved by thrombin at arginine-1689. The basis for this failure was identified by polymerase chain reaction amplification of exon 14 of the variant factor VIII genes and direct sequencing of the amplified products. In both cases, a single base substitution (C to T) was identified that produces an arginine to cysteine substitution at amino acid residue 1689. These data identify the molecular defects of the two identical factor VIII variant proteins. The dysfunctional factor VIII has been designated "Factor VIII-East Hartford," the residence of the patient in whom the defect was first identified.

Estudo citofotométrico da expressão do marcador tumoral Fator VIII e fatores prognósticos no adenocarcinoma gástrico Cytophotometric study of the expression of the tumoral marker Factor VIII and prognostic factors in gastrci adenocarcinoma

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Mary Tossa Nakamura

2007-12-01

ção III ou IV apresentaram índice de marcagem maiores do que aqueles com Bormann I ou II, porém sem correlação com a profundidade de invasão tumoral, grau de diferenciação, envolvimento nodal e padrão histológico. CONCLUSÕES: O presente estudo identificou e marcou 95,24% das amostras para o Fator VIII. Em relação aos fatores prognósticos não houve correlação significativa exceto entre o Fator VIII e a classificação de Bormann no qual o tipo III ou IV foi maior que o tipo I ou II.INTRODUCTION: Regarding gastric cancer, the incidence, diagnosis and therapeutic options showed improvement in the last decades, but prognosis remains gloomy, specially due the fact that most patients, already diagnosed present advanced tumors, metastatic and not liable to be surgically resected. Molecular biology is an area in science, which can give the answer to many questions and current scientific facts show that the this should be through detection of tumoral markers. The great advances in informatics refined cell image analysis by image cytophotometry makes it possible to study cell proliferation and angiogenesis in various tumor processes using immunohistochemistry and several markers. At present, studies are conducted to demonstrate the prognostic value of their expressions, however, in gastric adenocarcinoma the results have been divergent and studies are scarce. AIM: To identify and quantify the expression of cell proliferation markers using Ki-67 and of angiogenesis with Factor VIII in gastric adenocarcinoma using cytophotometry, and compare their expressions with factors such as Bormanns´ classification, tumor invasion depth, degree of differentiation, nodal involvement, histologic pattern and age. METHODS: Twenty-one patients with gastric adenocarcinoma identified between 1998 and 2006 were studied. Ki-67 and Factor VIII expressions were performed using immunohistochemistry with clone MIB-1 primary antibodies, monoclonal for Ki-67 and policlonal for Factor VIII

Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A.

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Johnson, D J; Pemberton, S; Acquila, M; Mori, P G; Tuddenham, E G; O'Brien, D P

1994-04-01

A novel CRM+ mutation, factor VIII position 373 serine to leucine substitution (FVIII 373-Leu) was identified during a survey of Factor VIII (FVIII) mutations. We have purified the variant protein from the patient's plasma in order to allow further characterisation of the molecule. The CRM+ plasma contained 120% Factor VIII antigen (FVIII:Ag) and 6% Factor VIII coagulant activity (FVIII:C). After purification the mutant FVIII was subjected to thrombin proteolysis, and was thereby activated 5.6-fold compared with 7-fold for wild type molecule. Subsequently, spontaneous inactivation of the mutant was much slower than noted for wild type FVIII. Western blot analysis using monoclonal antibodies demonstrated that thrombin cleavage of FVIII 373-Leu at positions 740 and 1689 were normal but that cleavage at position 372 was completely absent. Crystallographic coordinates of the active site of thrombin complexed to fibrinopeptide A were used to explore possible mechanistic reasons for the failure of thrombin to cleave the mutant FVIII at position 372. Steric hindrance between the mutant side chain and the side chain of the P1 residue was apparent. We conclude that the functional defect of FVIII 373-Leu results from the inability of thrombin to cleave the mutant at position 372-373, and propose that this is due to steric hindrance by the side chain of leucine 373, preventing correct formation of the enzyme substrate complex.

Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

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Marina E Fomin

Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

Factoring nonviral gene therapy into a cure for hemophilia A.

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Gabrovsky, Vanessa; Calos, Michele P

2008-10-01

Gene therapy for hemophilia A has fallen short of success despite several clinical trials conducted over the past decade. Challenges to its success include vector immunogenicity, insufficient transgene expression levels of Factor VIII, and inhibitor antibody formation. Gene therapy has been dominated by the use of viral vectors, as well as the immunogenic and oncogenic concerns that accompany these strategies. Because of the complexity of viral vectors, the development of nonviral DNA delivery methods may provide an efficient and safe alternative for the treatment of hemophilia A. New types of nonviral strategies, such as DNA integrating vectors, and the success of several nonviral animal studies, suggest that nonviral gene therapy has curative potential and justifies its clinical development.

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...

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

Science.gov (United States)

Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

Science.gov (United States)

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and

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.

Haemophilia A: Database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene

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Tuddenham, E.G.D. (Clinical Research Centre, Harrow (United Kingdom)); Cooper, D.N. (Thrombosis Research Inst., London (United Kingdom)); Gitschier, J. (Univ. of California, San Francisco (United States)); Higuchi, M.; Kazazian, H.H.; Antonarakis, S.E. (Johns Hopkins Univ., Baltimore (United States)); Hoyer, L.W. (American Red Cross, Rockville (United States)); Yoshioka, A. (Nara Medical Coll., Kashihara City (Japan)); Peake, I.R. (Royal Hallamshire Hospital, Sheffield (United Kingdom)); Schwaab, R. (Inst. fuer Klinische Biochemie der Univ. Bonn (West Germany)); Lavergne, J.M. (Hopital de Bicetre (France)); Giannelli, F. (Guy' s Hospital, London (United Kingdom))

1991-09-25

Mutations at the factor VIII gene locus causing Haemophilia A have now been identified in many patients from a many ethnic groups. Earlier studies used biased methods which detected repetitive mutations at a few CG dinucleotides. More recently rapid gene scanning methods have uncovered an extreme diversity of mutations. Over 80 different point mutations, 6 insertions, 7 small deletions, and 60 large deletions have been characterized. Repetitive mutation has been proved for at least 16 CpG sites. All nonsense mutations cause severe disease. Most missense mutations appear to cause instability of the protein, but some are associated with production of dysfunctional factor VIII molecules, thereby localizing functionally critical regions of the cofactor. Variable phenotype has been observed in association with three of the latter class of genotype. This catalogue of gene lesions in Haemophilia A will be updated annually.

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

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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.

Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

DEFF Research Database (Denmark)

Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

2018-01-01

activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...

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

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

DEFF Research Database (Denmark)

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...... = 10) receiving three needle induced knee joint bleeds 14 days apart and a control group (n = 9) receiving three sham procedures. Three hours after each injury/sham 50 IU kg−1 rhFVIII was administrated intravenously. Subsequently, both groups continued rhFVIII treatment for another 9 weeks. Binding...

Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

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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.

Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A

DEFF Research Database (Denmark)

Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth

2007-01-01

examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...

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

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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.

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

Science.gov (United States)

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

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

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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.

[Effective immunosuppresive therapies including steroid pulse treatment for intramuscular hematoma in iliopsoas in acquired hemophilia].

Science.gov (United States)

Mohri, Hiroshi; Tanabe, Juichi; Takagi, Hiroshi; Murata, Takashi

2007-12-01

Acquired hemophilia is a life-threatening bleeding disorder by the development of autoantibody against factor VIII. The therapeutic approach relies on steroid, cyclophosphamide and/or cyclosporine. A 64-year-old man was referred to our hospital with extensive hematoma in both psoas muscles, severe anemia of 6.8 g/dl, prolonged activated partial thromboplastin time over 200 seconds, and factor VIII coagulation activity (FVIII: C) of 1.9%. A factor VIII inhibitor was detected at 118 Bethesda units (BU). The diagnosis of acquired hemophilia was made in the absence of a detectable cause. The inhibitor was IgG with a subclass of IgG4 and reacted with 72 kDa fragment of factor VIII light chain. Steroid pulse therapy following steroid treatment resulted in the resolution of acquired hemophila with marked and prolonged efficacy.

Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease

International Nuclear Information System (INIS)

Girma, J.P.; Ardaillou, N.; Meyer, D.; Lavergne, J.M.; Larrieu, M.J.

1979-01-01

Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125 I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (lgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125 I-Fab fragments of goat anti-F.VIII/WF antiserum than intact goat lgG or rabbit lgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of vWd and varying concentrations of anti-F.VIII/WF Fab fragments (rabbit or goat) confirmed the decreased antigenic reactivity of variant F.VIII/WF

An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum

International Nuclear Information System (INIS)

Peake, I.R.; Bloom, A.L.; Giddings, J.C.; Ludlam, C.A.

1979-01-01

An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measured antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 0 C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia. (author)

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

Science.gov (United States)

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

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

Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

NARCIS (Netherlands)

Collins, P. W.; Blanchette, V. S.; Fischer, K.; Bjorkman, S.; Oh, M.; Fritsch, S.; Schroth, P.; Spotts, G.; Astermark, J.; Ewenstein, B.

Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1).

Structural Instability in Ice VIII under Pressure

International Nuclear Information System (INIS)

Besson, J.; Klotz, S.; Hamel, G.; Marshall, W.; Nelmes, R.; Loveday, J.

1997-01-01

Below 125K, tetragonal ice VIII remains in a metastable form at ambient pressure. This form has long been considered to be identical to ice VIII, although unexplained discrepancies exist between their vibrational spectra. Neutron diffraction studies reveal an isostructural phase transformation below 2GPa related to a weakening of the bonds between the two D 2 O sublattices of ice VIII. In this new phase, ice VIII ' , the tetragonal distortion is 20% larger than in ice VIII, which accounts for the differences between the vibrational frequencies of the two phases. copyright 1997 The American Physical Society

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...

Descripción de un inmunoensayo enzimático que reconoce anticuerpos anti-factor VIII/von Willebrand obtenidos a partir de hibridomas múridos Description of an enzime immunoassay that recognizes anti-factor VIII/von Willebrand antibodies obtained from murine hybridomas

Directory of Open Access Journals (Sweden)

Renée González Sampedro

1999-04-01

Full Text Available Se describe un inmunoensayo enzimático (ELISA que detecta anticuerpos anti-Factor-VIII/von Willebrand (FVIII/vW, con una relación de enlace > 5, que permite reconocer dichos anticuerpos tempranamente en los cultivos de hibridomas múridos. Para la adsorción de las placas del inmunoensayo se utilizaron preparados semipurificados de FVIII/vW obtenidos en Cuba. Se inmunizaron ratones Balb/c con la finalidad de generar los anticuerpos monoclonales detectados por este ELISA. Se obtuvo un clon con crecimiento estable y varios subclones positivos por el ELISA con actividad biológica específica de anticuerpos inhibidores de FVIIIAn enzime immunoassay (ELISA that detects anti-Factor VIII/von Willebrand (FVIII/vw antibodies with a binding relationship > 5 that allows the early recognition of such antibodies in the cultures of murine hybridomas is described. Semipurified preparations of FVIII/vw obtained in Cuba were used for the adsorption of the immunoassay plates. Balb/c mice were immunized in order to generate the monoclonal antibodies detected by this ELISA. A clone with stable growth and several positive subclones were obtained by ELISA with specific biological activity of FVIII-inhibiting antibodies

The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

Science.gov (United States)

Hu, Min; Hu, Haoyu; Cai, Wei; Mo, Zhikang; Xiang, Nan; Yang, Jian; Fang, Chihua

2018-05-01

Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

Genotype and phenotype report on patients with combined deficiency of factor V and factor VIII in Iran.

Science.gov (United States)

Karimi, Mehran; Cairo, Andrea; Safarpour, Mohammad M; Haghpanah, Sezaneh; Ekramzadeh, Maryam; Afrasiabi, Abdolreza; Shahriari, Mahdi; Menegatti, Marzia

2014-06-01

Combined factor V (FV) and factor VIII (FVIII) deficiency is a rare autosomal recessive bleeding disorder characterized by mild-to-moderate bleeding. Epistaxis, postsurgical bleeding and menorrhagia are the most common symptoms. The aim of this study is to report the phenotype-genotype characterization carried out in patients affected with combined FV and FVIII deficiency from Iran. A cross-sectional study was conducted in Shiraz Hemophilia Center, southern Iran. Twelve cases, seven men and five women coming from eight families were included in our study after taking consent form. Coagulation activity for all patients was measured. All exons and intron-exon junctions of lectin mannose binding protein 1 (LMAN1) gene and multiple coagulation factor deficiency 2 genes were amplified by PCR, and subsequently sequenced by the Sanger method. Patients[Combining Acute Accent] age ranged from 6 to 59 years mean ± SD: 23.8 ± 15.4 years and median: 22 years. No patient presented with severe bleeding symptom. Only one patient had severe FV and FVIII deficiency (both factor levels stop codon. Larger studies are needed to calculate the correlation between factor levels, genetic and bleeding symptoms.

Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

Science.gov (United States)

Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

2012-01-01

Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

Recent pharmacological management of oral bleeding in hemophilic patient

Directory of Open Access Journals (Sweden)

Monica Widyawati Setiawan

2011-09-01

Full Text Available Background: Hemophilia is a hereditary bleeding disorder that can increase the risk of disease in oral cavity. Sometimes hemophilia is not always established already in a patient. The lack of awareness of hemophilia presence can cause serious problem. Purpose: The purpose of this review is to explain about dental bleeding manifestation and management in hemophilic patient. Reviews: Hemophilia can be manifested as dental bleeding that cannot stop spontaneously. It should be treated with factor VIIII either by giving whole blood, fresh plasma, fresh frozen plasma, cryoprecipitate, and factor VIII concentrate. Factor VIII dose for hemophilia treatment can be calculated based on factor VIII present in hemophilia patient’s body. Factor VIII can also be given as prophylaxis to prevent bleeding. Complications that can be caused by factor VIII replacement therapy are the presence of factor VIII inhibitor and transfusion related diseases. Treatment of dental bleeding due to hemophilia consists of factor replacement therapy and supportive therapy. Conclusion: Treatment of dental bleeding due to hemophilia consists of factor replacement therapy and supportive therapy. There are complications that can happen due to factor VIII replacement therapy that should be considered and anticipated.Latar belakang: Hemofilia adalah kelainan pembekuan darah yang diturunkan. Hemophilia dapat meningkatkan resiko penyakit rongga mulut. Hemofilia tidak selalu sudah terdiagnosa saat penderita melakukan kunjungan ke dokter gigi. Kurangnya kewaspadaan akan adanya hemofilia dapat menyebabkan masalah serius. Tujuan: Tujuan dari kajian pustaka ini adalah memaparkan tentang manifestasi dan penanganan perdarahan gigi pada penderita hemofilia. Tinjauan pustaka: hemofilia dapat bermanifestasi sebagai perdarahan gigi yang tidak dapat berhenti secara spontan. Pada keadaan perdarahan tersebut, pemberian faktor VIII yang diberikan sebagai whole blood, fresh plasma, fresh frozen plasma

Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

Science.gov (United States)

Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G

2015-06-01

Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates.

Science.gov (United States)

Azzi, A; Ciappi, S; Zakvrzewska, K; Morfini, M; Mariani, G; Mannucci, P M

1992-03-01

Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high-purity concentrates reduces the risk of B19 transmission, we have prospectively evaluated the rate of anti-B19 seroconversion in two groups of susceptible (anti-B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20).

Assessing patients' and caregivers' perspectives on stability of factor VIII products for haemophilia A

DEFF Research Database (Denmark)

DiBenedetti, D B; Coles, T M; Sharma, T

2014-01-01

Haemophilia A is a rare inherited bleeding disorder characterized by an inability of the blood to clot normally. Patients can experience spontaneous or trauma-induced joint and soft tissue bleeding and must keep coagulation factor VIII (FVIII) accessible at all times; thus, FVIII product storage...... challenges with storing FVIII products, especially storage away from home. More than half preferred storing FVIII products at room temperature vs. in the refrigerator for long periods of time. FVIII product accessibility, usage and storage affect disease management. Results support the need for more...... convenient and accessible FVIII products for patients in daily life and while travelling. In addition, the use of social media has potential value in recruiting this population....

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

Science.gov (United States)

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

Staining for factor VIII related antigen and Ulex europaeus agglutinin I (UEA-I) in 230 tumours. An assessment of their specificity for angiosarcoma and Kaposi's sarcoma.

Science.gov (United States)

Leader, M; Collins, M; Patel, J; Henry, K

1986-11-01

In this study we examined the staining reactivity of commercially available antisera to factor VIII related antigen (F VIII RAg) and Ulex europaeus agglutinin I (UEA-I) on sections from 230 formalin fixed paraffin embedded tumours. These included 196 sarcomas, 20 carcinomas and 14 angiomas. All angiomas showed positive staining for F VIII RAg; all carcinomas showed negative staining; the vasoformative areas of all angiosarcomas stained positively but only four of six angiosarcomas showed positive staining of their solid areas; of seven Kaposi's sarcomas, all showed positive staining of vessels and six showed positive staining of the spindle cell component. In the remaining 181 non-vascular sarcomas there was a false positive result in four tumours (2.2%), three of which had a history of irradiation. Pre-radiotherapy biopsies of these three tumours stained negatively with anti-F VIII RAg. UEA-I was demonstrated in all the angiomas studied, in all angiosarcomas (including the solid components) and in well-formed vessels of all Kaposi's sarcomas, but only in the spindle cell component of 3/6. However, there was an unacceptably high rate of false positive staining amongst the carcinomas and non-vascular sarcomas. In conclusion, F VIII RAg is a specific but not a sensitive marker of angiosarcomas; UEA-I is a sensitive but not a specific marker of angiosarcomas.

Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

Science.gov (United States)

Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

1986-06-01

Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

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

Science.gov (United States)

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

2014-01-01

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. PMID:25339360

Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea Attainment and characterization of murine monoclonal anti-factor VIII antibodies

Directory of Open Access Journals (Sweden)

Rosana Rossi-Ferreira

2006-06-01

Full Text Available Entre os avanços da engenharia celular e biotecnologia nas últimas décadas, destaca-se a produção de anticorpos monoclonais murinos (AcMm utilizados no aprimoramento diagnóstico nas rotinas laboratoriais. A produção de fator VIII de alta pureza sempre foi o desejo e a preocupação das indústrias de hemoderivados para tratamento de pacientes portadores de hemofilia A, porém este produto inexiste no Brasil, sendo necessária sua obtenção no mercado internacional a custos elevados. O trabalho tem por objetivo a produção de AcMm anti-fator VIII humano (FVIII H através da expansão dos clones e caracterização imunoquímica do anticorpo. Camundongos Balb/c foram imunizados com FVIII H purificado como também proveniente de crioprecipitado e as células esplênicas dos animais foram fusionadas com células mielomatosas murinas segundo o método descrito por Kohler e Milstein para produção de híbridos em cultura. Foram testados 1.983 híbridos dos quais 105 foram submetidos à clonagem. Destes, 39 obtiveram monoclonalidade e 7 destes clones foram caracterizados através de técnicas de immunoblotting. Foram submetidas à purificação por cromatografia três imunoglobulinas de diferentes classes pertencentes aos clones LAMB1-10A1A4, LAMB1-17A1A1 e LAMB1-24A2A1. A imunoglobulina purificada pertencente ao clone LAMB1-10A1A4 foi adsorvida em coluna de imunoafinidade para purificação de concentrado de FVIII proveniente de crioprecipitado plasmático.Among the advances in cellular engineering and biotechnology over the last decades, the production of murine monoclonal antibodies (AcMm, used to improve laboratory diagnoses, stands out. The production of very pure factor VIII has always been a concern of suppliers of blood products to treat patients with hemophilia A and this product is still not produced in Brazil. Hence, it can only be attained on the international market at a high cost. The aim of this work was to produce AcMm anti-factor

[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.

Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis

NARCIS (Netherlands)

Valentino, L. A.; Pipe, S. W.; Collins, P. W.; Blanchette, V. S.; Berntorp, E.; Fischer, K.; Ewenstein, B. M.; Oh, M.; Spotts, G.

2016-01-01

Introduction: We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been

Diagnostic accuracy study of a factor VIII ELISA for detection of factor VIII antibodies in congenital and acquired haemophilia A.

Science.gov (United States)

Batty, Paul; Moore, Gary W; Platton, Sean; Maloney, James C; Palmer, Ben; Bowles, Louise; Pasi, K John; Rangarajan, Savita; Hart, Daniel P

2015-10-01

Antibody formation to factor VIII (FVIII) remains the greatest clinical and diagnostic challenge to the haemophilia-treating physician. Current guidance for testing for inhibitory FVIII antibodies (inhibitors) recommends the functional Nijmegen-Bethesda assay (NBA). A FVIII ELISA offers a complementary, immunological approach for FVIII antibody testing. It was the aim of this study to retrospectively evaluate the performance of a FVIII ELISA (index) for detection of FVIII antibodies, compared with the NBA (reference). All samples sent for routine FVIII antibody testing at two haemophilia Comprehensive Care Centres, were tested in parallel using the NBA and a solid-phase, indirect FVIII ELISA kit (Immucor). A total of 497 samples from 239 patients (severe haemophilia A=140, non-severe haemophilia A=85, acquired haemophilia A=14) were available for analysis. Sixty-three samples tested positive by the NBA (prevalence 12.7%, 95% confidence interval [CI], 9.9-15.9 %), with a median inhibitor titre of 1.2 BU/ml (range 0.7-978.0). The FVIII ELISA demonstrated a specificity of 94.0% (95%CI, 91.3-96.0), sensitivity of 77.8% (95%CI, 65.5-87.3), negative predictive value of 96.7% (95%CI, 94.5-98.2), positive predictive value 65.3% (95%CI, 53.5-76.0), negative likelihood ratio 0.2 (95%CI, 0.1-0.4), positive likelihood ratio 13.0 (95%CI, 8.7-19.3) and a diagnostic odds ratio of 54.9 (95%CI, 27.0-112.0). Strong positive correlation (r=0.77, pNBA (log adjusted) and FVIII ELISA optical density. In conclusion, FVIII ELISA offers a simple, specific, surveillance method enabling batch testing of non-urgent samples for the presence of FVIII antibodies.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Science.gov (United States)

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

[Ehler-Danlos syndrome type VIII].

Science.gov (United States)

Ciarloni, L; Perrigouard, C; Lipsker, D; Cribier, B

2010-03-01

Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of diseases involving genetic collagen fibre impairment. We describe a case of a patient presenting the rare type VIII, in which dermatitis ocre was associated with parodontal disease, and which was diagnosed late. A 29-year-old man consulted for a pretibial ulcer present for seven years, resulting from a post-traumatic haematoma that had failed to heal. In view of the longiliner morphology, it had previously been diagnosed as Marfan syndrome. Subsequently, edentation was observed as well as "alveolar bone fragility". Examination revealed a marfanoid morphotype, a pretibial ulcer set within long-standing bilateral dermatitis ocre and papyraceous scars, but no joint hyperlaxity or cutaneous hyperelasticity. The diagnosis was consequently corrected to EDS type VIII. Type VIII is a rare form of EDS, and the molecular mechanism is poorly understood. The involvement of parodontal connective tissue suggests impairment of collagen I and III proteins. It is important to identify this type of the disease since it involves parodontal disease for which early treatment is required in order to try to prevent edentation. The present case demonstrates the importance of diagnosis, which may be based upon appearance of bilateral dermatitis ocre from the age of 15 years associated with skin fragility. This sign is not part of the classical picture of Marfan syndrome, with which EDS type VIII is often confounded. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Transgenic rabbits as a model organism for production of human clotting factor VIII

International Nuclear Information System (INIS)

Vasicek, D.; Chrenek, P.; Makarevich, A.; Bauer, M.; Jurcik, R.; Suvegova, K.; Rafay, J.; Bulla, J.; Hetenyi, L.; Erickson, J.; Paleyanda, R.K.

2005-01-01

Human clotting factor VIII (hFVIII) is a very complex and large protein whose expression is difficult, as hFVIII requires extensive post-translational modification to be biologically active. This paper reports the generation of transgenic rabbits as a model species for testing the expression of hFVIII in the mammary gland. For micro-injection, a fusion gene construct was used, consisting of 2.5 kb murine whey acidic protein (mWAP) promoter, 7.2 kb cDNA of hFVIII, and 4.6 kb of 3' flanking sequences of the mWAP gene. from 130 micro-injected zygotes transferred into recipients, 30 offspring were delivered. The pups were screened for the transgene by PCR, using DNA isolated from the ear, and results were confirmed by Southern blot analysis. The transgene was identified in one female founder animal, and it was transmitted to the offspring in a Mendelian fashion, thus demonstrating stable integration of the gene construct into the germline of the transgenic rabbits. (author)

77 FR 64401 - Order of Succession for HUD Region VIII

Science.gov (United States)

2012-10-19

... Region VIII AGENCY: Office of Field Policy and Management, HUD. ACTION: Notice of Order of Succession... Field Offices (Region VIII). This Order of Succession supersedes all previous Orders of Succession for HUD Region VIII. DATES: Effective Date: October 9, 2012. FOR FURTHER INFORMATION CONTACT: Lawrence D...

Radiation therapy in pseudotumour haemarthrosis

International Nuclear Information System (INIS)

Lal, P.; Biswal, B.M.; Thulkar, S.; Patel, A.K.; Venkatesh, R.; Julka, P.K.

1998-01-01

Total or partial deficiency of factor VIII and IX in the coagulation cascade leads to haemophilia. Haemophilia affecting weight-bearing joints gives a 'pseudotumour' or haemarthrosis-like condition. Surgery and cryoprecipitate infusions have been the treatment for this condition. Radiocolloids and radiation therapy have been used with some benefit. One case of ankle pseudotumour which was treated by low-dose external beam radiation is presented here. Copyright (1998) Blackwell Science Pty Ltd

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

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Cimino E

2014-12-01

Full Text Available Ernesto Cimino,1 Silvia Linari,2 Mara Malerba,3 Susan Halimeh,4 Francesca Biondo,5 Martina Westfeld5 1Dipartimento Medicina Clinica e Sperimentale, Universita’ degli Studi di Napoli Federico II, Naples, Italy; 2Agenzia per l’ Emofilia, AOU Careggi di Firenze, Florence, Italy; 3Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi “A Bianchi Bonomi”, Milan, Italy; 4CRC Coagulation Research Centre GmbH, Duisburg, Germany; 5Pfizer Italia, Rome, Italy Introduction: Hemophilia A treatment involves replacing the deficient coagulation factor VIII. This process may involve multiple steps that might create a barrier to adherence. A new dual-chamber syringe (DCS; FuseNGo® was recently introduced with the aim of simplifying reconstitution. Aim: This study aimed to identify factors associated with adult patients’ preferences for different coagulation factor VIII reconstitution systems and to test ease of use and patient preference for the DCS. Methods: A cross-sectional survey of adults with hemophilia A in five European countries was conducted; a subset of subjects also participated in a practical testing session of the DCS. Results: Among the 299 survey participants, the device scenario requiring the least equipment and reconstitution steps (the DCS received a median preference rating of 71 out of 100 (0 being “the least desirable” and 100 “the most desirable” rating. This was significantly higher than the other scenarios (the next highest achieved a median of 50 points; P<0.001. Participants would be more likely to use this device prophylactically (P<0.001. Among the 98 participants who tested the DCS, 57% preferred this device over their current device, 26% preferred their current device, and 17% had no preference. The DCS was rated as easier to use than current treatment devices (median score 9/10 versus 7/10 for current treatment, P=0.001. Conclusion: The survey indicates that the prefilled DCS, Fuse

Murine leukemia virus-derived retroviral vector has differential integration patterns in human cell lines used to produce recombinant factor VIII

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Marcela Cristina Correa de Freitas

2014-06-01

Full Text Available OBJECTIVE: Nowadays recombinant factor VIII is produced in murine cells including in Chinese hamster ovary (CHO and baby hamster kidney cells (BHK. Previous studies, using the murine leukemia virus-derived retroviral vector pMFG-FVIII-P140K, modified two recombinant human cell lines, HepG2 and Hek293 to produce recombinant factor VIII. In order to characterize these cells, the present study aimed to analyze the integration pattern of retroviral vector pMFG-FVIII-P140K.METHODS: This study used ligation-mediated polymerase chain reaction to locate the site of viral vector integration by sequencing polymerase chain reaction products. The sequences were compared to genomic databases to characterize respective clones.RESULTS: The retroviral vector presented different and non-random profiles of integration between cells lines. A preference of integration for chromosomes 19, 17 and 11 was observed for HepG2FVIIIdB/P140K and chromosome 9 for Hek293FVIIIdB/P140K. In genomic regions such as CpG islands and transcription factor binding sites, there was no difference in the integration profiles for both cell lines. Integration in intronic regions of encoding protein genes (RefSeq genes was also observed in both cell lines. Twenty percent of integrations occurred at fragile sites in the genome of the HepG2 cell line and 17% in Hek293.CONCLUSION: The results suggest that the cell type can affect the profile of chromosomal integration of the retroviral vector used; these differences may interfere in the level of expression of recombinant proteins.

Elevated Factor VIII and von Willebrand Factor Levels Predict Unfavorable Outcome in Stroke Patients Treated with Intravenous Thrombolysis

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Noémi Klára Tóth

2018-01-01

Full Text Available IntroductionPlasma factor VIII (FVIII and von Willebrand factor (VWF levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS patients and to find out whether they predict long-term outcomes.Materials and methodsStudy population included 131 consecutive AIS patients (median age: 69 years, 60.3% men who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA. Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS. ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS.ResultsVWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS <6:189.6% (151.9–233.2%; NIHSS 6–16: 199.6% (176.4–250.8%; NIHSS >16: 247.8% (199.9–353.8%, p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001 but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299, most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender

Radiation therapy in pseudotumour haemarthrosis

Energy Technology Data Exchange (ETDEWEB)

Lal, P.; Biswal, B.M.; Thulkar, S.; Patel, A.K.; Venkatesh, R.; Julka, P.K. [Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi (India). Departments of Radiation Oncology, Radiodiagnosis and Haematology

1998-11-01

Total or partial deficiency of factor VIII and IX in the coagulation cascade leads to haemophilia. Haemophilia affecting weight-bearing joints gives a `pseudotumour` or haemarthrosis-like condition. Surgery and cryoprecipitate infusions have been the treatment for this condition. Radiocolloids and radiation therapy have been used with some benefit. One case of ankle pseudotumour which was treated by low-dose external beam radiation is presented here. Copyright (1998) Blackwell Science Pty Ltd 14 refs., 2 figs.

Extended analyses of Se VII and Se VIII

International Nuclear Information System (INIS)

Vankleef, Th.A.M.; Joshi, Y.N.

1984-01-01

Joshi et al. (1984) have conducted an analysis of the 3d8 4s-3d8 4p transitions in As VII. The present investigation is concerned with an analysis of similar transitions in Se VIII. The selenium spectrum was photographed in the 400-1200-A wavelength region on a variety of normal-incidence spectrographs. Attention is given to least-squares-fit (LSF) and Hartree-Fock (HF) parameter values for the 3d9 4d configuration of Se VII, LSF and HF parameter values for the 3d8 4s and 3d8 4p configurations of Se VIII, the energy and composition of the levels of the 3d9 4d configuration of Se VII, classified lines in Se VII, energy levels and composition of the 3d8 4s configuration and the revised and newly determined levels of the 3d8 4p configuration of Se VIII, and newly classified lines of Se VIII. 15 references

4p-5s transitions in YVII, VIII, ZrVIII, IX, NbIX, X and MoX, XI

International Nuclear Information System (INIS)

Rahimullah, K.; Chaghtai, M.S.Z.; Khatoon, S.

1976-01-01

The spectra of Y VII, VIII, Zr VIII, IX, Nb X and Mo X, XI are studied for the first time and the 1971 analysis of Nb IX is improved. By analyses of the transitions 4s 2 4psup(k)-4s 2 4psup(k-1)5s all the levels of the configurations 4p 3 , 4p 2 5s, 4p 2 and 4p5s are established in the spectra concerned. (Auth.)

Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

Science.gov (United States)

McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

2015-07-01

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.

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...

Ehlers-Danlos Syndrome Type VIII: A Rare Cause of Leg Ulcers in Young Patients

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Sophie Ronceray

2013-01-01

Full Text Available Ehlers-Danlos syndrome type VIII (EDS-VIII is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII.

Complexation of the cesium cation with lithium ionophore VIII: extraction and DFT study

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Novák, Vít; Vaňura, P.; Bouř, Petr

2013-01-01

Roč. 298, č. 3 (2013), s. 2065-2068 ISSN 0236-5731 Institutional support: RVO:61388963 Keywords : cesium cation * lithium ionophore VIII * complexation * extraction and stability constants * water-nitrobenzene system * DFT calculations * structures Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 1.415, year: 2013

Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

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Rios, Danyelle R A; Fernandes, Ana Paula; Figueiredo, Roberta C; Guimarães, Daniela A M; Ferreira, Cláudia N; Simões E Silva, Ana C; Carvalho, Maria G; Gomes, Karina B; Dusse, Luci Maria Sant' Ana

2012-05-01

Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

Science.gov (United States)

van Velzen, A S; Eckhardt, C L; Peters, M; Leebeek, F W G; Escuriola-Ettingshausen, C; Hermans, C; Keenan, R; Astermark, J; Male, C; Peerlinck, K; le Cessie, S; van der Bom, J G; Fijnvandraat, K

2017-07-01

Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Background Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg -1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians

Milk fat globule-epidermal growth factor-factor VIII attenuates sepsis-induced acute kidney injury.

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Cen, Cindy; Aziz, Monowar; Yang, Weng-Lang; Zhou, Mian; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

2017-06-01

Acute kidney injury (AKI) is most commonly caused by sepsis in critically ill patients, and it is associated with high morbidity and mortality. The pathophysiology of sepsis-induced AKI is generally accepted to include direct inflammatory injury, endothelial cell dysfunction, and apoptosis. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in the enhancement of apoptotic cell clearance and regulation of inflammation. We hypothesize that administration of recombinant mouse MFG-E8 (rmMFG-E8) can protect mice from kidney injuries caused by sepsis. Sepsis was induced in 8-wk-old male C57BL/6 mice by cecal ligation and puncture (CLP). rmMFG-E8 or phosphate-buffered saline (vehicle) was injected intravenously at a dosage of 20 μg/kg body weight at time of CLP (n = 5-8 mice per group). After 20 h, serum and renal tissue were harvested for various analyses. The renal injury markers blood urea nitrogen (BUN) and creatinine were determined by enzymatic and chemical reactions, respectively. The gene expression analysis was carried out by real-time quantitative polymerase chain reaction. At 20 h after CLP, serum levels of BUN and creatinine were both significantly increased in the vehicle group compared with the sham group, whereas the mice treated with rmMFG-E8 had a significant reduction in BUN and creatinine levels by 28% and 24.1%, respectively (BUN: 197.7 ± 23.6 versus 142.3 ± 20.7 mg/dL; creatinine: 0.83 ± 0.12 versus 0.63 ± 0.06 mg/dL; P sepsis through inhibiting the production of proinflammatory cytokines and chemokine, as well as through the activation of endothelial cells. Thus, MFG-E8 may have a therapeutic potential for treating AKI induced by sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Agnostic stacking of intergalactic doublet absorption: measuring the Ne VIII population

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

2018-05-01

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 path-length 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 normalization 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 value significantly lower that than predicted by recent simulations. We translate this density into an estimate of the baryon density Ωb ≈ 1.8 × 10-3, constituting 4 per cent of the total baryonic mass.

Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

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Maartje van den Biggelaar

Full Text Available BACKGROUND: 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 proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

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.

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

Science.gov (United States)

Liu, Xia; Chen, Xiaogang; Yang, Jiezuan; Guo, Renyong

2017-09-01

Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

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

African Journals Online (AJOL)

The labour ward analgesic service at King Edward VIII. Hospital, Durban. D. A. ROCKE, C. C. ROUT, H. D. RUSSELL, S. SINGH. Abstract The provision of analgesic services to the labour ward at King Edward VIII Hospital was studied during a I-week period. Of249 patients, 113 (45%) received no analgesia whatsoever.

Thermoelectrical properties of the compounds ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt)

Energy Technology Data Exchange (ETDEWEB)

Oestreich, J; Probst, U; Richardt, F; Bucher, E [University of Konstanz, PO Box X916, D-78457 Konstanz (Germany)

2003-02-05

The research into new materials with good thermoelectric properties has revealed new compounds consisting of metallic elements (Bando Y, Suemitsu T, Takagi K, Tokushima H, Echizen Y, Katoh K, Umeo K, Maeda Y and Takabatake T 2000 J. Alloys Compounds 313 1-6, Ghelani N, Loo S, Chung D, Sportouch S, Nardi S, Kanatzidis M, Hogan T and Nolas G 2000 Mater. Res. Soc. 626 Z8.6.1). The half-Heusler compound ZrNiSn, in particular, shows promising thermoelectric properties and has been studied by many scientists during recent years (Uher C, Hu S, Yang J, Meisner G P and Morelli D T 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 485-8, Romaka L P, Stadnyk Yu V, Goryn A M, Gorelenko Yu K and Skolozdra R V 1997 Proc. ICT'97: 16th Int. Conf. on Thermoelectrics pp 516-19, Hohl H, Ramirez A P, Goldmann C, Ernst G, Woelfing B and Bucher E 1998 J. Phys.: Condens. Matter 11 1697-709, Oestreich J, Kaefer W, Richardt F, Probst U and Bucher E 1999 Proc. 5th European Workshop on Thermoelectrics pp 192-5). In an effort to find new thermoelectric materials, the half-Heusler compounds of the groups ScM{sup VIII}Sb and YM{sup VIII}Sb (M{sup VIII} = Ni, Pd, Pt) were synthesized by arc melting and the thermoelectric properties were examined by standard characterization methods. Doping experiments showed that it is possible to change the electrical properties of the compounds while retaining the half-Heusler structure. Within the two groups, YPtSb showed the best thermoelectrical properties. At a temperature of 400 K the electrical conductivity of YPtSb is 748{omega}{sup -1} cm{sup -1} and the Seebeck coefficient is 116.3{mu}V K{sup -1}. The thermal conductivity at 400 K extrapolated using the Wiedemann-Franz law is 2.87 W K{sup -1} m{sup -1}. This leads to a dimensionless figure of merit of 0.14.

Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

Science.gov (United States)

Yonezawa, S; Maruyama, I; Sakae, K; Igata, A; Majerus, P W; Sato, E

1987-10-01

Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

Antihemophilic factor (recombinant plasma/albumin-free method for the management and prevention of bleeding episodes in patients with hemophilia A

Directory of Open Access Journals (Sweden)

Steven Pipe

2009-02-01

Full Text Available Steven PipeDepartment of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USAAbstract: Hemophilia is a rare genetic bleeding disorder that, if not adequately controlled, is associated with life-threatening bleeding events and serious and costly complications, primarily from joint damage. The advent of effective clotting factor replacement therapy for patients with hemophilia is considered one of the foremost medical advances of the 20th century. The last 3 decades of experience in hemophilia care have witnessed the effectiveness of the care of patients with hemophilia within specialized comprehensive care centers, advances in factor replacement therapies, the benefits of prophylaxis over on-demand replacement therapy, and the role of aggressive management of joint disease to prevent dysfunction. Ongoing challenges, including the management of inhibitors to factor therapies and the consequences of thousands of patients with hemophilia becoming infected with human immunodeficiency virus and hepatitis C virus in the 1980s from contaminated plasma-derived factor concentrates, have highlighted the need for vigilance with respect to clotting factor product safety, access to care, and a full complement of choice of factor replacement therapies. Advate® (antihemophilic factor [recombinant] plasma/albumin-free method [rAHF-PFM] is the first recombinant factor VIII therapy manufactured without human or animal protein additives to eliminate the risk of pathogen transmission that could be carried by these additives. Preclinical studies established bioequivalence with recombinant antihemophilic factor (Recombinate®, a product with 16 years of clinical experience. Currently licensed in 44 countries worldwide, rAHF-PFM has over 7 years of clinical research within 5 global studies supporting its safety and efficacy in the treatment of patients with hemophilia A.Keywords: factor VIII, hemophilia A, recombinant proteins, clinical

New study on the XeVIII spectrum

International Nuclear Information System (INIS)

Gallardo, M.; Raineri, M.; Giuliani, M.; Lagorio, C.; Padilla, S.; Sarmiento, R.; Reyna Almandos, J.G.

2005-01-01

Capillary light sources were used to observe the spectrum of seven-times-ionized xenon, XeVIII, in the 300-6000 A wavelength range. Twenty-eight energy levels belonging to the 5s-9s, 5d-9d, 5g-9g, 7i-10i, 9l, 5p-9p, 4f-9f, 6h-9h and 8k-10k configurations were adjusted and 38 new spectral lines were classified. The XeVIII ionization energy was determined with improved accuracy using the polarization model. The analysis was supported by Hartree-Fock calculations. The weighted oscillator strengths for all the observed spectral lines were also calculated considering the fitted values for the energy parameters

New study on the XeVIII spectrum

Energy Technology Data Exchange (ETDEWEB)

Gallardo, M. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: gallardom@ciop.unlp.edu.ar; Raineri, M. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: monicar@ciop.unlp.edu.ar; Giuliani, M. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Lagorio, C. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Padilla, S. [Dto. de Fisica, Fac. de C. Exactas y Naturales, Universidad Nacional de Mar del Plata Funes 3350 (7600) Mar del Plata (Argentina); Sarmiento, R. [Dto. De Fisica, Universidad del Atlantico, A.A 1890 Barranquilla (Colombia); Reyna Almandos, J.G. [Centro de Investigaciones Opticas (CIOp) Casilla de Correo 124, 1900 La Plata (Argentina)]. E-mail: jreyna@ciop.unlp.edu.ar

2005-10-15

Capillary light sources were used to observe the spectrum of seven-times-ionized xenon, XeVIII, in the 300-6000 A wavelength range. Twenty-eight energy levels belonging to the 5s-9s, 5d-9d, 5g-9g, 7i-10i, 9l, 5p-9p, 4f-9f, 6h-9h and 8k-10k configurations were adjusted and 38 new spectral lines were classified. The XeVIII ionization energy was determined with improved accuracy using the polarization model. The analysis was supported by Hartree-Fock calculations. The weighted oscillator strengths for all the observed spectral lines were also calculated considering the fitted values for the energy parameters.

Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

Science.gov (United States)

Dodt, J; Hubbard, A R; Wicks, S J; Gray, E; Neugebauer, B; Charton, E; Silvester, G

2015-07-01

A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed. © 2015 John Wiley & Sons Ltd.

Lithium ionophore VIII as an extraordinarily effective receptor for the strontium cation: Experimental and theoretical study

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Novák, Vít; Vaňura, P.; Bouř, Petr

2014-01-01

Roč. 1061, Mar 5 (2014), s. 110-113 ISSN 0022-2860 Institutional support: RVO:61388963 Keywords : strontium cation * lithium ionophore VIII * complexation * extraction and stability constants * DFT calculations * structures Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.602, year: 2014

Extracorporeal adsorption of anti-factor VIII allo-antibodies on randomly functionalized polystyrene resins.

Science.gov (United States)

Huguet, Hélène-Céline; Lasne, Dominique; Rothschild, Chantal; Siali, Rosa; Jozefonvicz, Jacqueline

2004-02-01

The occurrence of anti-factor VIII (FVIII) allo-antibodies is a severe complication of the treatment of haemophilia A patients, leading to the inhibition of transfused FVIII activity. The effective elimination of these inhibitory antibodies plays a decisive role in the management of affected patients. To achieve this, immunoadsorption devices employing synthetic adsorbers, which selectively eliminate inhibitors, are of interest in the treatment strategy of haemophilia A patients with inhibitors. Adsorbers consisting of polystyrene-based beads substituted with sulphonate and L-tyrosyl methylester groups, which mimic part of epitope of FVIII molecule recognized by inhibitors, exhibit selective binding capacities towards anti-FVIII antibodies. The adsorption of FVIII inhibitors was investigated by simulating an extracorporeal circulation of haemophilic plasma over these functionalized resins. These innovative adsorbers are able to remove around 25% of anti-FVIII antibodies in 15 minutes depending on the plasma tested. Furthermore, they do not modify the amount of essential plasmatic proteins or residual immunoglobulins G. Experiments which were carried out using different plasmas with various inhibitor titres demonstrate a good reproducibility regarding the adsorption capacity of the synthetic resin. The characteristics of adsorption are similar on either native or regenerated resins. Both the purely synthetic nature of the resin and its easy processability demonstrate the real advantages over currently available protocols. This synthetic adsorber is a major technological advance in selective removal of FVIII inhibitory antibodies.

Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

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Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

2017-01-01

ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

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…

Use of routine histopathology and factor VIII-related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs.

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Giuffrida, M A; Bacon, N J; Kamstock, D A

2017-12-01

Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII-RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA. © 2016 John Wiley & Sons Ltd.

A post-marketing safety and efficacy assessment of a monoclonal antibody purified high-purity factor VIII concentrate.

Science.gov (United States)

Hay, C R; Lee, C A; Savidge, G

1996-01-01

The identification of infrequent side-effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post-marketing surveillance. We present a post-marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow-up period of 284 days (range 1-1074), and a total follow-up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate-P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate-P, were carried out, mostly for routine haemarthroses or prophylaxis. No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate-P. Post-marketing surveillance or nationally organized pharmaco-vigilance should be practiced more widely to enable identification of low-frequency side-effects of treatment.

Limit of detection and threshold for positivity of the Centers for Disease Control and Prevention assay for factor VIII inhibitors.

Science.gov (United States)

Miller, C H; Boylan, B; Shapiro, A D; Lentz, S R; Wicklund, B M

2017-10-01

Essentials Immunologic methods detect factor VIII (FVIII) antibodies in some inhibitor-negative specimens. Specimens were tested by modified Nijmegen-Bethesda assay (NBA) and fluorescence immunoassay. The NBA with preanalytical heat inactivation detects FVIII inhibitors down to 0.2 NBU. IgG 4 frequency validates the established threshold for positivity of ≥ 0.5 NBU for this NBA. Background The Bethesda assay for measurement of factor VIII inhibitors called for quantification of positive inhibitors by using dilutions producing 25-75% residual activity (RA), corresponding to 0.4-2.0 Bethesda units, with the use of 'more sensitive methods' for samples with RA closer to 100% being recommended. The Nijmegen modification (Nijmegen-Bethesda assay [NBA]) changed the reagents used but not these calculations. Some specimens negative by the NBA have been shown to have FVIII antibodies detectable with sensitive immunologic methods. Objective To examine the performance at very low inhibitor titers of the Centers for Disease Control and Prevention (CDC)-modified NBA (CDC-NBA), which includes preanalytic heat inactivation to liberate bound anti-FVIII antibodies. Methods Specimens with known inhibitors were tested with the CDC-NBA. IgG 4 anti-FVIII antibodies were measured by fluorescence immunoassay (FLI). Results Diluted inhibitors showed linearity below 0.4 Nijmegen-Bethesda units (NBU). With four statistical methods, the limit of detection of the CDC-NBA was determined to be 0.2 NBU. IgG 4 anti-FVIII antibodies, which correlate most strongly with functional inhibitors, were present at rates above the background rate of healthy controls in specimens with titers ≥ 0.2 NBU and showed an increase in frequency from 14.3% at 0.4 NBU to 67% at the established threshold for positivity of 0.5 NBU. Conclusions The CDC-NBA can detect inhibitors down to 0.2 NBU. The FLI, which is more sensitive, demonstrates anti-FVIII IgG 4 in some patients with negative (NBA, supporting the need for

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...

Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

International Nuclear Information System (INIS)

Marlar, R.A.; Griffin, J.H.

1981-01-01

To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

Myosin VIII regulates protonemal patterning and developmental timing in the moss Physcomitrella patens.

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Wu, Shu-Zon; Ritchie, Julie A; Pan, Ai-Hong; Quatrano, Ralph S; Bezanilla, Magdalena

2011-09-01

Plants have two classes of myosins. While recent work has focused on class XI myosins showing that myosin XI is responsible for organelle motility and cytoplasmic streaming, much less is known about the role of myosin VIII in plant growth and development. We have used a combination of RNAi and insertional knockouts to probe myosin VIII function in the moss Physcomitrella patens. We isolated Δmyo8ABCDE plants demonstrating that myosin VIII is not required for plant viability. However, myosin VIII mutants are smaller than wild-type plants in part due to a defect in cell size. Additionally, Δmyo8ABCDE plants produce more side branches and form gametophores much earlier than wild-type plants. In the absence of nutrient media, Δmyo8ABCDE plants exhibit significant protonemal patterning defects, including highly curved protonemal filaments, morphologically defective side branches, as well as an increase in the number of branches. Exogenous auxin partially rescues protonemal defects in Δmyo8ABCDE plants grown in the absence of nutrients. This result, together with defects in protonemal branching, smaller caulonemal cells, and accelerated development in the Δmyo8ABCDE plants, suggests that myosin VIII is involved in hormone homeostasis in P. patens.

VIII Olimpíada Brasileira de Astronomia e Astronáutica

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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.

Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

Energy Technology Data Exchange (ETDEWEB)

Fong, I.; Lai, P.S.; Ouah, T.C. [National Univ. of Singapore (Malaysia)] [and others

1994-09-01

The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

The vestibulocochlear nerve (VIII).

Science.gov (United States)

Benoudiba, F; Toulgoat, F; Sarrazin, J-L

2013-10-01

The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. Copyright © 2013. Published by Elsevier Masson SAS.

The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

Science.gov (United States)

Stephenson, Kenna; Neuenschwander, Pierre F; Kurdowska, Anna K

2013-01-01

/or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women. The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic, ischemic, or neuronal injury. Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of androgens of DHEA and Testosterone if indicated. Experimental subjects were monitored for 36 months. Baseline, 2-month, and annual values were obtained for: blood pressure, body mass index, fasting glucose, Homeostasis Metabolic Assessment of Insulin Resistance (HOMA-IR), fasting triglycerides, total Factor VII, Factor VIII, fibrinogen, Antithrombin III, Plasminogen Activator Inhibitor1(PAL-1), C-reactive protein (CRP), Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Tumor Necrosis Factor-alpha (TNF), Insulin-like Growth Factor (IGF-1), and sex steroid levels. Psychosocial measures included: Greene Climacteric Scale, Visual Analog Pain Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Holmes Rahe Stress Scale, Job Strain, and Home Strain. Health outcome measures included the number of prescribed medications used, number of co-morbidities, and endometrial thickness in postmenopausal women with intact uteri. Subjects receiving compounded transdermal bioidentical hormone therapy showed significant favorable changes in: Greene Climacteric Scale scores, Hamilton Anxiety Scale, Hamilton Depression Scale, Visual Analog Pain Scale, fasting glucose, fasting triglycerides, MMP-9, C-reactive Protein, fibrinogen, Factor VII, Factor VIII, Insulin-Like Growth Factor 1, and health outcomes of co-morbidities and a number of prescribed medications. Antithrombin III levels were significantly decreased at 36 months. All other measures did not exhibit significant effects. Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic

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

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...... stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass...

Practical experience and lessons learned through implementation of Appendix VIII performance demonstration requirements

International Nuclear Information System (INIS)

Ashwin, P.J.; Becker, F.L.; Latiolais, C.L.; Spanner, J.C.

1996-01-01

To provide the US nuclear industry with a uniform implementation of the Performance Demonstration requirements within the 1989 edition of ASME Section XI, Appendix VIII, representatives from all US nuclear utilities formed the Performance Demonstration Initiative (PDI). The PDI recognized the potential benefits that Appendix VIII offered the nuclear industry and initiated a proactive approach to implement the requirements. In doing so it was expected that performance demonstration of ultrasonic examination procedures would allow for improvement in the efficiency and credibility of inservice inspection to be realized. Explicit within the performance demonstration requirements of Appendix VIII is the need for a Performance Demonstration Administrator, a difficult requirement to fulfill. Not only must the administrator exhibit the attributes of understanding the demonstration requirements, but also have solid technical knowledge, integrity and be able to interface with the industry at all levels, from operations to regulatory. For the nuclear industry, the EPRI NDE Center is an obvious choice to fulfill this position. This paper provides a brief background of the PDI, a nuclear industry-wide initiative to implement the performance demonstration requirements of Appendix VIII. Even though the consensus approach adopted by the PDI is discussed, the paper's primary objective is to provide examples of the lessons learned by the Center through the specific requirements of Appendix VIII

Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

Directory of Open Access Journals (Sweden)

Jason Echavez Abello

2016-10-01

Full Text Available In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time. We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value < 0.05. The study included 16,357 admitted Dengue cases. The reported cases included a majority of children (70.09%, mild cases of the disease (64.00%, patients from the public sector (69.82%, and non-tertiary hospitals (62.76%. Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (p<0.05. The severe type of the disease was more likely to be admitted late than the mild type (p<0.05. Late admission was also more likely in public hospitals than in private hospitals (p<0.05; and within tertiary level hospitals than non-tertiary hospitals (p<0.05. Late admission was more likely during the non-epidemic period than the 2010 epidemic period (p<0.05. A case fatality rate of 1 or greater was significantly associated with children, severe diseases, tertiary hospitals and public hospitals when admitted late (p<0.05. Data suggests that early admission among child cases was common in Region VIII. This behavior is encouraging, and should be continued. However, further study is needed

Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

Science.gov (United States)

Abello, Jason Echavez; Gil Cuesta, Julita; Cerro, Boyd Roderick; Guha-Sapir, Debarati

2016-10-01

In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time). We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value Dengue cases. The reported cases included a majority of children (70.09%), mild cases of the disease (64.00%), patients from the public sector (69.82%), and non-tertiary hospitals (62.76%). Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (pDengue guidelines in order to standardize the admission criteria and time across hospitals.

Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II).

Science.gov (United States)

Kavakli, K; Yang, R; Rusen, L; Beckmann, H; Tseneklidou-Stoeter, D; Maas Enriquez, M

2015-03-01

BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. To demonstrate superiority of prophylaxis vs. on demand therapy with BAY 81-8973 in patients with severe hemophilia A. In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30 IU kg(-1)), 3-times-weekly prophylaxis (30-40 IU kg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs)and immunogenicity were also assessed. Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported. Twice weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.

Intrinsic clotting factors in dependency of age, sex, body mass index, and oral contraceptives: definition and risk of elevated clotting factor levels.

Science.gov (United States)

Luxembourg, Beate; Schmitt, Joern; Humpich, Marek; Glowatzki, Matthias; Seifried, Erhard; Lindhoff-Last, Edelgard

2009-10-01

Elevated clotting factors have been demonstrated to be a risk factor for venous thromboembolism (VTE). The aim of our study was to investigate the impact of age, sex, body mass index, and oral contraceptives on the clotting factor activities of factors VIII, IX, XI, and XII and their impact on the cutoff definition and risk of VTE associated with elevated clotting factors. Factor VIII, IX, XI, and XII activities were measured in 499 blood donors and 286 patients with VTE. Age and body mass index predicted significantly and independently the clotting factor activities of factors VIII, IX, and XI, whereas use of oral contraceptives predicted factor IX, XI, and XII levels. Percentiles of clotting factor activities, which are often used for the cutoff definition of elevated clotting factors, varied due to the effect of age, body mass index, and oral contraceptives. The adjusted odds ratios for VTE were 10.3 [95% confidence interval (CI) 5.1-20.7], 6.1 (95% CI 3.1-12.0), and 3.3 (95% CI 1.9-5.8) for elevated factors VIII, IX, and XI, respectively. Furthermore, our study demonstrates for the first time that elevated factor XII is associated with an increased risk of VTE (adjusted odds ratio 2.9, 95% CI 1.6-5.3).

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"

Valor preditivo da expressão dos anticorpos Antifator VIII no carcinoma epidermóide do esôfago Predictive value of antifactor VIII antibody expression in squamous cell carcinoma of the esophagus

Directory of Open Access Journals (Sweden)

Sebastião Gonzaga Barbosa-Neto

2007-12-01

to progress knowledge on protein expression alterations for such neoplasia. AIM: To quantify protein expression implicated in the angiogenesis process and correlate to clinical-pathological features. METHODS: Using immunohistochemistry procedure, cytophotometric imaging by SAMBA, 29 sampled-tissue embedded in paraffin blocks of squamous cell carcinoma of the esophagus were analyzed. Clinical criteria, such as age and gender, as well as histophatological criteria, such as differentiated grade features, size and tumor location, were considered. Parameters evaluated were labeling index and optical density. The marker used in the present study was antifactor VIII. RESULTS: Verification on the expression of the marker in labeling index parameter was greater than optical density. Factor VIII presented homogeneous reading out. Labeling index was 80,17 + 10,40 (P=0,073 and optical density 51,25 + 11,02 (P=0,245. CONCLUSION: Protein expression reading analysis involved in angiogenesis process allows to define subgroups according to differentiated grade carcinoma, tumoral staging, size and tumor localization, although it does not allow association with gender and patient age. Optical density for factor VIII does not have statistical significant expression in any subgroup evaluated.

Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

Science.gov (United States)

Gaboulaud, Valérie; Parquet, Armelle; Tahiri, Cedric; Claeyssens, Ségolène; Potard, Valérie; Faradji, Albert; Peynet, Jocelyne; Costagliola, Dominique

2002-02-01

Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 risk transmission between albumin-stabilized recombinant factor and plasma-derived factor, we studied the prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children between 1 and 6-years of age who had previously been treated with albumin-stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti-B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti-B19 was found in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates than in children treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8), independently of the other factors studied.

Henry VIII, McLeod syndrome and Jacquetta's curse.

Science.gov (United States)

Stride, P; Lopes Floro, K

2013-01-01

The mental decline of King Henry VIII from being a jovial, charismatic and athletic young man into an increasingly paranoid, brutal tyrant in later life, ever more concerned at his lack of one or more male heirs, has attracted many medical diagnostic theories. Previous hypotheses have included diabetes, syphilis and hypothyroidism, among others. However, these inadequately explain Henry's failure to produce a male heir, despite multiple pairings. The latest postulated diagnoses for Henry are the coexistence of both Kell blood group antigenicity (possibly inherited from Jacquetta Woodville, Henry's maternal great grandmother) causing related impaired fertility, and McLeod syndrome, causing psychotic changes. As the mutated McLeod protein of the syndrome significantly reduces the expression, effectively inactivating the Kell antigen, we critically review this theory, examining in detail the pathophysiology of these conditions and assessing the genealogy of Henry VIII and its effect in subsequent generations.

Evidence for the formation of sodium hassate(VIII)

International Nuclear Information System (INIS)

Zweidorf, A. von; 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.

2004-01-01

Hassium, element 108, was produced in the fusion reaction between 26 Mg and 248 Cm. The hassium recoils were oxidized in-situ to a highly volatile oxide, presumably HsO 4 , and were transported in a mixture of He and O 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 α-decay chains of Hs were detected in the first 5 detectors centred around detection position 3. In analogy to OsO 4 , which forms Na 2 [OsO 4 (OH) 2 ], an osmate(VIII), with aqueous NaOH, HsO 4 presumably was deposited as Na 2 [HsO 4 (OH) 2 ], a hassate(VIII). (orig.)

The spectrum and term system of S VIII

International Nuclear Information System (INIS)

Bengtsson, P.; Jupen, C.; Engstroem, L.; Redfors, A.; Westerlind, M.

1993-01-01

The spectrum of seven times ionized sulfur, S VIII, has been observed in the wavelength range 50-1200 A. Both beam-foil and laser-produced plasma light sources have been used. 71 new lines representing the transitions 2p 5 -2p 4 3d, 2p 4 3s-3p, 3p-3d, 3d-4f, 4f-5g and 5g-6h have been identified and 100 energy levels, of which 46 are new, are now accurately established. The spectral analysis is supported by isoelectronic comparisons along the F I-sequence and by parametric least-squares fits of Slater integrals to the observed levels. The ionization potential in S VIII is determined to 2 651 899 ± 60 cm -1 and estimated ionization energies are derived for the isoelectronic elements between F I and Ar X. (orig.)

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

Desmopressin acetate as a haemostatic elevator in individuals with combined deficiency of factors V and VIII: a clinical trial.

Science.gov (United States)

Mansouritorghabeh, H; Shirdel, A

2016-02-01

ESSENTIALS: Combined factor V (FV) and factor VIII (FVIII) deficiency (CF5F8D) is an autosomal recessive coagulation disorder. Desmopressin acetate (DDAVP) was intravenously infused in 20 adult patients with CF5F8D. DDAVP can enhance FVIII levels but has no effect on FV levels in patients with CF5F8D. DDAVP can be substituted for FVIII concentrates in patients with CF5F8D. Combined factor V (FV) and FVIII deficiency (CF5F8D) is a rare inherited autosomal recessive double-gene disorder most frequently seen in the Middle East. Although affected individuals have deficiency of two coagulation factors (range 5-30%), their bleeding tendencies are similar to patients who have deficiency of a single coagulation factor at the same level. The mainstay of their treatment is infusion of FVIII concentrate and fresh frozen plasma. Here, the effect of intravenous infusion of desmopressin acetate (DDAVP) on elevation of coagulation FV and FVIII was investigated through a clinical trial in May 2015. In a registered controlled trial, DDAVP (dosage 0.3 μg kg(-1) ) was intravenously infused into 20 adult patients with CF5F8D over 20 min. After an hour, blood samples were collected and plasma levels of FV and FVIII were measured. This study revealed that DDAVP can enhance FVIII levels but has no effect on FV plasma concentration in patients with CF5F8D. Based on these findings, FVIII concentrates may be substituted for DDAVP in patients with CF5F8D. © 2015 International Society on Thrombosis and Haemostasis.

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... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Organic Compounds for Which Residues...

40 CFR Appendix Viii to Part 268 - LDR Effective Dates of Injected Prohibited Hazardous Wastes

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false LDR Effective Dates of Injected Prohibited Hazardous Wastes VIII Appendix VIII to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION... to Part 268—LDR Effective Dates of Injected Prohibited Hazardous Wastes National Capacity LDR...

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".

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.

Spectrophotometric determination of hydrogen peroxide with osmium(VIII) and m-carboxyphenylfluorone.

Science.gov (United States)

Hoshino, Mitsuru; Kamino, Shinichiro; Doi, Mitsunobu; Takada, Shingo; Mitani, Shota; Yanagihara, Rika; Asano, Mamiko; Yamaguchi, Takako; Fujita, Yoshikazu

2014-01-03

Spectrophotometric determination of hydrogen peroxide was accomplished with osmium(VIII) and m-carboxyphenylfluorone (MCPF) in the presence of cetyltrimethylammonium chloride (CTAC). In the determination of hydrogen peroxide based on the fading of the color of osmium(VIII)-MCPF complex, Beer's law was obeyed in the range 20-406 ng mL(-1), with an effective molar absorption coefficient (at 580 nm) of 5.21×10(4) L mol(-1) cm(-1) and a relative standard deviation of 0.33% (n=6). Further, we performed the characterization of MCPF and obtained the crystal structure. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

DEFF Research Database (Denmark)

Johansson, Pär I; Ostrowski, Sisse R

2010-01-01

Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.......Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX....

D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

Science.gov (United States)

Agorasti, Athanasia; Trivellas, Theodoros; Mourvati, Efthimia; Papadopoulos, Vasilios; Tsatalas, Konstantinos; Vargemezis, Vasilios; Passadakis, Ploumis

2013-06-01

The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P 168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

Advanced therapies for the treatment of hemophilia: future perspectives.

Science.gov (United States)

Liras, Antonio; Segovia, Cristina; Gabán, Aline S

2012-12-13

Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression.

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

Science.gov (United States)

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.

Time Transfer Experiment by TCE on the ETS-VIII Satellite

National Research Council Canada - National Science Library

Nakagawa, Fumimaru; Takahashi, Yasuhiro; Amagai, Jun; Tabuchi, Ryo; Hama, Shin'ichi; Hosokawa, Mizuhiko

2007-01-01

.... At NICT, we developed Time Comparison Equipment (TCE) both onboard ETS-VIII and in the Earth station for precise time transfer between the atomic clocks on the satellite and a ground reference clock...

INSIGHT in risk factors and treatment of inhibitors in nonsevere hemophilia A

NARCIS (Netherlands)

van Velzen, A.S.

2016-01-01

Hemophilia A is an inherited X-linked bleeding disorder that occurs in male offspring of carrier females. In these individuals a mutation in the F8 gene, located on the X-chromosome, causes a deficiency of the factor VIII protein, clotting factor VIII. The worldwide prevalence of hemophilia is 1 in

Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.

Science.gov (United States)

Collins, P W; Blanchette, V S; Fischer, K; Björkman, S; Oh, M; Fritsch, S; Schroth, P; Spotts, G; Astermark, J; Ewenstein, B

2009-03-01

The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level break-through bleeding in patients with severe hemophilia A on prophylaxis. This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. These data have important implications for the management of patients with severe hemophilia.

Mechanistic aspects of Os(VIII) catalysed oxidation of loop diuretic ...

Indian Academy of Sciences (India)

furosemide by Ag(III) periodate complex in aqueous alkaline medium. SHWETA J .... Os(VIII) catalysed DPA oxidation, the order in [OH. −. ] ... Victoria-3170, Australia) connected to a rapid ..... follows. The furosemide, periodate and hydroxide ion.

An Acquired Factor VIII Inhibitor in a Patient with HIV and HCV: A Case Presentation and Literature Review

Directory of Open Access Journals (Sweden)

S. B. Zeichner

2013-01-01

Full Text Available Introduction. Despite its low incidence, acquired factor VIII inhibitor is the most common autoantibody affecting the clotting cascade. The exact mechanism of acquisition remains unclear, but postpartum patients, those with autoimmune conditions or malignancies, and those with exposure to particular drugs appear most susceptible. There have been several case reports describing acquired FVIII inhibitors in patients receiving interferon alpha for HCV treatment and in patients being treated for HIV. To our knowledge, this is the first case of a patient with HCV and HIV who was not actively receiving treatment for either condition. Case Presentation. A 57-year-old Caucasian male with a history of HIV and HCV was admitted to our hospital for a several day history of progressively worsening right thigh bruising and generalized weakness. CTA of the abdominal arteries revealed large bilateral retroperitoneal hematomas. Laboratory studies revealed the presence of a high titer FVIII inhibitor. Conclusion. Our case of a very rare condition highlights the importance of recognizing and understanding the diagnosis of acquired FVIII inhibitor. Laboratory research and clinical data on the role of newer agents are needed in order to better characterize disease pathogenesis, disease associations, genetic markers, and optimal disease management.

Status and trend analysis of prophylactic usage of recombinant factor VIII in Chinese pediatric patients with hemophilia A: ReCare - a retrospective, phase IV, non-interventional study.

Science.gov (United States)

Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Vicky; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

2017-09-01

No study has reported the status and chronological trend of prophylactic recombinant factor VIII (rFVIII) use in Chinese pediatric patients with hemophilia A (HA). We aimed to analyze the status and trend of rFVIII-containing prophylaxis in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained REgular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers across China. The trend of prophylaxis was evaluated by determining the mean duration of prophylaxis, mean injection frequency (per week), mean dose of each injection (IU/kg), mean total dose injected/week (IU) and proportion of rFVIII consumption relative to factor VIII (FVIII) consumption over the study period. We analyzed 183 male pediatric patients with HA (mean age, 7.1 ± 4.23 years), who received intermittent prophylaxis between 1 November 2007 and 31 May 2013. The mean duration of prophylaxis with rFVIII increased from 16.72 weeks in 2008 to 32.77 in 2012. Per injection dose of rFVIII increased significantly from 2008 to 2013 (25.89 to 28.31 IU/kg, p < .001). An increase was also reported in the mean total FVIII consumed (699.97 ± 173.25 IU in 2008 and 891.30 ± 730.341 in 2013) and mean proportion of rFVIII used (33.33 ± 57.73% in 2008 to 85.50 ± 29.077% in 2013). Our data revealed an overall improvement in treatment dosage and duration with an increase in the number of patients receiving prophylaxis. The total proportion of rFVIII also increased gradually indicating the development of economy and safety awareness. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02263066).

PERSEPSI SISWA KELAS VIII TENTANG KESEHATAN REPRODUKSI REMAJA DAN PENYAKIT MENULAR SEKSUAL

Directory of Open Access Journals (Sweden)

Omega Rianda Rustian

2015-06-01

This study is based on interviews conducted in one of the BK school teacher. This study aimed to determine the perception class VIII student perceptions on adolescent reproductive health and sexually transmitted diseases in SMP Islam Sultan Agung 1 Semarang. The method used in this research is descriptive quantitative survey methods. Population in this research is class VIII SMP Islam Sultan Agung 1 Semarang totaling 151 students with a sampling technique used is accidental to obtain a sample of 60. Data collection tools in the form of a psychological scale with data analysis techniques using descriptive analysis percentage. The average result of students' perceptions on adolescent reproductive health in the high category (74% and perceptions of students about sexually transmitted diseases in the very high category (76%. That class VIII SMP Islam Sultan Agung 1 Semarang already have an idea of the meaning of adolescent reproductive health is a state of good health both physically healthy, functioning, as well as reproductive performance in adolescent and the  meaning of sexually transmitted diseases are caused by viruses, parasites, or function as a result of sexual intercourse.

Influencing factors of radioiodine therapy in hyperthyroidism in adults

International Nuclear Information System (INIS)

Xu Jiehua; Zhang Zikang; Cheng Muhua; Wu Chunxing; Wang Ping; Shan Hong

2007-01-01

The study was to evaluate factors affecting outcome of 131 I therapy in hyperthyroidism for optimizing the method. Data from 213 patients who received 131 I treatment from July 2003 to July 2005 in our department were retrospectively analyzed. Factors possibly contributing to the outcome of the 1311 therapy were analyzed, including gender, age, history of antithyroid drag, thyroid volume, duration of disease and radioactive iodine uptake rate. Multivariate analysis was done. The rates of euthyroidism and hypothyroidism were 69% and 8.5%, respectively, after one time 131 I therapy. Multivariate analysis of the patients showed no statistically significant factors affecting the outcome of 131 I therapy. The study showed that 131 I dose can be directly calculated, and this simplifies the dose-determined method and individualizes the therapy. (authors)

Polymorphisms in the F8 gene and MHC-II variants as risk factors for the development of inhibitory anti-factor VIII antibodies during the treatment of hemophilia a: a computational assessment.

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Gouri Shankar Pandey

Full Text Available The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6 of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants. Using a computational binding predictor, we were able to expand our analysis to (a include all wild type peptides spanning each polymorphic position; and (b consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population. Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes

Mysterious bruises

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H Chen

2012-01-01

Full Text Available A 69-year-old man presented with multiple spontaneous bruises in the past 2 weeks. Several large-sized hematomas were found on examination. The initial investigation revealed a prolonged activated partial thromboplastin time (aPTT with normal platelet count and international normalized ratio. Further investigation revealed a low factor VIII activity secondary to presence of factor VIII inhibitor, making the diagnosis of acquired hemophilia A. Further work-up revealed that pernicious anemia was present and acted as an associated disease. After steroids therapy, his aPTT was normalized and the factor VIII inhibitor titer became undetectable. 2 months later, a relapse occurred and new hematomas appeared at his retropharyngeal space and left arm. His bleeding was controlled by administration of recombinant factor VIIa, and a combined therapy of intravenous steroids and rituximab was given to eradicate the inhibitor. The approach to workup of bleeding disorders as well as treatment of acquired hemophilia A are herein discussed.

Class VIII Medical Materiel Controls in the U.S. European Command

National Research Council Canada - National Science Library

1991-01-01

.... Class VIII medical materiel inventories are maintained as part of the U.S. war reserve stocks to ensure military readiness and to provide needed health care during wartime or contingencies. The U.S...

Genetic engineering for haemophilia A.

Science.gov (United States)

Gan, Shu Uin; Kon, Oi Lian; Calne, Roy Y

2006-10-01

At first sight, haemophilia A would appear to be an ideal candidate for treatment by gene therapy. There is a single gene defect; cells in different parts of the body, but especially the liver, produce Factor VIII, and only 5% of normal levels of Factor VIII are necessary to prevent the serious symptoms of bleeding. This review attempts to outline the status of gene therapy at present and efforts that have been made to overcome the difficulties and remaining problems that require solving. Undoubtedly, success will be achieved, but it is likely that considerably more work will be necessary before experimental models can be introduced into the clinic with any likelihood of success. The most successful results in animals that may have clinical application were from introducing the Factor VIII gene to newborn animals before antibodies are produced, presumably inducing a state of tolerance.

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

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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%,

Compact invariant sets of the Bianchi VIII and Bianchi IX Hamiltonian systems

International Nuclear Information System (INIS)

Starkov, Konstantin E.

2011-01-01

In this Letter we prove that all compact invariant sets of the Bianchi VIII Hamiltonian system are contained in the set described by several simple linear equalities and inequalities. Moreover, we describe invariant domains in which the phase flow of this system has no recurrence property and show that there are no periodic orbits and neither homoclinic, nor heteroclinic orbits contained in the zero level set of its Hamiltonian. Similar results are obtained for the Bianchi IX Hamiltonian system. -- Highlights: → Zero level set of Hamiltonian of Bianchi VIII/IX systems contains no periodic orbits. → Similar conditions for homoclinic/heteroclinic orbits are given. → General nonexistence conditions of compact invariant sets are got.

Compact invariant sets of the Bianchi VIII and Bianchi IX Hamiltonian systems

Energy Technology Data Exchange (ETDEWEB)

Starkov, Konstantin E., E-mail: konst@citedi.mx [CITEDI-IPN, Av. del Parque 1310, Mesa de Otay, Tijuana, BC (Mexico)

2011-08-22

In this Letter we prove that all compact invariant sets of the Bianchi VIII Hamiltonian system are contained in the set described by several simple linear equalities and inequalities. Moreover, we describe invariant domains in which the phase flow of this system has no recurrence property and show that there are no periodic orbits and neither homoclinic, nor heteroclinic orbits contained in the zero level set of its Hamiltonian. Similar results are obtained for the Bianchi IX Hamiltonian system. -- Highlights: → Zero level set of Hamiltonian of Bianchi VIII/IX systems contains no periodic orbits. → Similar conditions for homoclinic/heteroclinic orbits are given. → General nonexistence conditions of compact invariant sets are got.

Porcine model of hemophilia A.

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Yuji Kashiwakura

Full Text Available Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8. Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.

Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA.

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Sahu S

1996-07-01

Full Text Available An 82 year old man developed antibodies against coagulation factor VIII:C without any apparent cause. Bleeding from the soft tissue cavity could not be controlled by factor VIII:C concentrates, immunosuppression with steroids and intravenous immunoglobulin therapy in the standard dosages. However, a single injection of Epsilon Aminocaproic Acid (EACA instilled into the cavity under aseptic precautions achieved lasting hemostasis with resultant wound healing.

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

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Pär I Johansson

2010-06-01

Full Text Available Pär I Johansson, Sisse R OstrowskiCapital Region Blood Bank, Section for Transfusion Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Recombinant activated factor VII (rFVIIa, NovoSeven® was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.Objective: To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders.Patients and methods: English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders.Results: Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies.Conclusion: The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual’s ability to generate thrombin and form a clot, and not on the patient’s weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.Keywords: hemophilia, inhibitors, coagulation factor VIII, coagulation factor IX, rFVIIa, NovoSeven, FEIBA, hemostasis, RCT

Role of VI/II ratio on the growth of ZnO nanostructures using chemical bath deposition

Energy Technology Data Exchange (ETDEWEB)

Urgessa, Z.N., E-mail: zelalem.urgessa@nmmu.ac.za [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Oluwafemi, O.S. [Department of Chemistry and Chemical Technology, Walter Sisulu University, Mthatha Campus, Private Bag XI, 5117 (South Africa); Botha, J.R. [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

2012-05-15

In this paper the growth process and morphological evolution of ZnO nanostructures were investigated in a series of experiments using chemical bath deposition. The experimental results indicate that the morphological evolution depends on the reaction conditions, particularly on OH{sup -} to Zn{sup 2+} ratio (which directly affects the pH). For low VI/II ratios, quasi-spherical nanoparticles of an average diameter 30 nm are obtained, whereas for larger VI/II ratios, nanorods with an average diameter less than 100 nm are produced, which indicates that by systematically controlling the VI/II ratio, it is possible to produce different shapes and sizes of ZnO nanostructures. A possible mechanism for the nanostructural change of the as-synthesized ZnO from particle to rod was elucidated based on the relative densities of H{sup +} and OH{sup -} in the solution.

Role of VI/II ratio on the growth of ZnO nanostructures using chemical bath deposition

International Nuclear Information System (INIS)

Urgessa, Z.N.; Oluwafemi, O.S.; Botha, J.R.

2012-01-01

In this paper the growth process and morphological evolution of ZnO nanostructures were investigated in a series of experiments using chemical bath deposition. The experimental results indicate that the morphological evolution depends on the reaction conditions, particularly on OH − to Zn 2+ ratio (which directly affects the pH). For low VI/II ratios, quasi-spherical nanoparticles of an average diameter 30 nm are obtained, whereas for larger VI/II ratios, nanorods with an average diameter less than 100 nm are produced, which indicates that by systematically controlling the VI/II ratio, it is possible to produce different shapes and sizes of ZnO nanostructures. A possible mechanism for the nanostructural change of the as-synthesized ZnO from particle to rod was elucidated based on the relative densities of H + and OH − in the solution.

PENGEMBANGAN KARAKTER KEDISIPLINAN DAN KEMAMPUAN PEMECAHAN MASALAH MELALUI MODEL LAPS-HEURISTIK MATERI LINGKARAN KELAS-VIII

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Sri Wahyuni

2015-08-01

Full Text Available Tujuan penelitian ini adalah untuk mengetahui (1 apakah pembelajaran dengan model pembelajaran LAPS-Heuristik pada materi lingkaran kelas-VIII dapat mengembangkan karakter kedisiplinan peserta didik, (2 apakah pembelajaran dengan model pembelajaran LAPS-Heuristik pada materi lingkaran kelas-VIII dapat meningkatkan kemampuan pemecahan masalah peserta didik, (3 apakah kemampuan pemecahan masalah matematika peserta didik yang diajar dengan model pembelajaran LAPS-Heuristik pada materi lingkaran kelas-VIII dapat mencapai kriteria ketuntasan minimal yang ditentukan. Desain penelitian ini adalah kualitatif deskriptif, artinya menggambarkan atau mendeskripsikan kejadian-kejadian yang menjadi pusat perhatian secara kualitatif dan berdasar data kualitatif. Penentuan sumber data dalam penelitian ini menggunakan teknik purposive sampling, yaitu dipilih dengan pertimbangan dan tujuan tertentu. Data diperoleh dengan observasi, wawancara, dan tes yang kemudian dianalisis menggunakan analisis kualitatif dan analisis gain untuk mengukur peningkatan. Analisis kualitatif menunjukkan karakter kedisiplinan dan kemampuan pemecahan masalah peserta didik meningkat, serta kemampuan pemecahan masalah peserta didik mencapai KKM melalui model pembelajaran LAPS-Heuristik.

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

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Mary Beth Callan

Full Text Available Severe hemophilia A (HA is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

Science.gov (United States)

Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

2017-02-01

Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

Glioneuronal Heterotopia Presenting As a Cerebellopontine angle Tumor of the cranial Nerve VIII, Case Report.

Science.gov (United States)

Peris-Celda, M; Giannini, C; Diehn, F E; Eckel, L J; Neff, B A; Van Gompel, J J

2018-04-03

Vestibular schwannomas and meningiomas account for the great majority of lesions arising in the cerebellopontine angle (CPA). In this report, we present a case of glioneuronal heterotopia, also known as glioneuronal hamartoma, arising from the VIII cranial nerve, which is an extremely uncommon lesion. Important radiologic and surgical aspects are reviewed, which may help in early recognition and intraoperative decision making when these lesions are encountered. A healthy 29-year-old female presented with intermittent right facial numbness. Magnetic resonance imaging (MRI) showed an incidental minimally enhancing cerebellopontine angle lesion on the right VII-VIII cranial nerve complex. The patient declined serial observation and opted for operative intervention for resection. Intraoperatively, the lesion resembled neural tissue and was continuous with the VIII cranial nerve. Pathological analysis demonstrated mature glioneuronal tissue consistent with hamartomatous brain tissue. The patient maintained normal hearing and facial nerve function after surgery. Radiologic, surgical and pathological characteristics are described. Ectopic glioneuronal tissue of the VIII cranial nerve is a rare non-neoplastic lesion, and should be considered in the differential diagnosis of unusual appearing intracanalicular and cerebellopontine angle lesions. The congenital and benign nature of this entity makes observation a valid option for these cases, although they are so infrequent that they are often presumptively managed as vestibular schwannomas. Attempts to radically resect these lesions may result in higher rates of hearing loss or facial palsy due to their continuity with the cranial nerves. Copyright © 2018 Elsevier Inc. All rights reserved.

Lacerations to Zones VIII and IX: It Is Not Just a Tendon Injury

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Charla R. Fischer

2011-01-01

Full Text Available Extensor tendon injuries are widely believed to be straightforward problems that are relatively simple to manage. However, these injuries can be complex and demand a thorough understanding of anatomy to achieve the best functional outcomes. When lacerations occur in the forearm as in Zones VIII and IX injury, the repair of the extensor tendon and muscle, and posterior interosseous nerve (PIN is often challenging. A review of the literature shows little guidance and attention for these injuries. We present four patients with injuries to Zones VIII and IX as well as a review of surgical technique, postoperative rehabilitation, and pearls that may be of benefit to those managing these injuries.

Role of Microvessel Density and Vascular Endothelial Growth Factor in Angiogenesis of Hematological Malignancies

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Rashika Chand

2016-01-01

Full Text Available Angiogenesis plays an important role in progression of tumor with vascular endothelial growth factor (VEGF being key proangiogenic factor. It was intended to study angiogenesis in different hematological malignancies by quantifying expression of VEGF and MVD in bone marrow biopsy along with serum VEGF levels and observing its change following therapy. The study included 50 cases of hematological malignancies which were followed for one month after initial therapy along with 30 controls. All of them were subjected to immunostaining by anti-VEGF and factor VIII antibodies on bone marrow biopsy along with the measurement of serum VEGF levels. Significantly higher pretreatment VEGF scores, serum VEGF levels, and MVD were observed in cases as compared to controls (p<0.05. The highest VEGF score and serum VEGF were observed in chronic myeloid leukemia and maximum MVD in Non-Hodgkin’s Lymphoma. Significant decrease in serum VEGF levels after treatment was observed in all hematological malignancies except for AML. To conclude angiogenesis plays an important role in pathogenesis of all the hematological malignancies as reflected by increased VEGF expression and MVD in bone marrow biopsy along with increased serum VEGF level. The decrease in serum VEGF level after therapy further supports this view and also lays the importance of anti angiogenic therapy.

PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

OpenAIRE

Apri Dwi Astuti

2012-01-01

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 ...

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)

Effects of Mg/Ga and V/III source ratios on hole concentration of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy

Science.gov (United States)

Nonoda, Ryohei; Shojiki, Kanako; Tanikawa, Tomoyuki; Kuboya, Shigeyuki; Katayama, Ryuji; Matsuoka, Takashi

2016-05-01

The effects of growth conditions such as Mg/Ga and V/III ratios on the properties of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy were studied. Photoluminescence spectra from Mg-doped GaN depended on Mg/Ga and V/III ratios. For the lightly doped samples, the band-to-acceptor emission was observed at 3.3 eV and its relative intensity decreased with increasing V/III ratio. For the heavily doped samples, the donor-acceptor pair emission was observed at 2.8 eV and its peak intensity monotonically decreased with V/III ratio. The hole concentration was maximum for the Mg/Ga ratio. This is the same tendency as in group-III polar (0001) growth. The V/III ratio also reduced the hole concentration. The higher V/III ratio reduced the concentration of residual donors such as oxygen by substituting nitrogen atoms. The surface became rougher with increasing V/III ratio and the hillock density increased.

EVALUATING THE EFFECTIVENESS OF PROPHYLACTIC REPLACEMENT THERAPY IN CHILDREN WITH HEMOPHILIC ARTHROPATHY IN DYNAMICS ON MAGNETIC RESONANCE IMAGING

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I. S. Remzantseva

2015-01-01

Full Text Available Modifications in treatment guidelines of hemophilic arthropathy changed the role of diagnostic X-ray imaging methods. Diagnostic methods are used both for determination of the degree of joint destruction and long-term evaluation of the joint conditions and therapy adequacy and effectiveness. Aim. Magnetic resonance imaging (MRI dynamics for joint condition assessment in children with hemophilic arthropathy receiving prophylactic factor replacement therapy concentrated rolling VIII. Materials and methods. We studied 13 boys aged 5 to 14 years (mean age 8.9 years with hemophilia type A severe form of the disease (factor VIII deficiency <1% at the baseline. The average age of appearance of hemarthrosis is 2.1 years (from 1.8 to 2.9 years. The frequency of bleeding into the joints of patients older than 1 year was 2-3 times per year. Magnetic resonance imaging (ToshibaExcelArtVantage, 1,5 T was performed in 13 patients, 35 joints were examined, 57 studies were executed. Control study of joints was conducted in 1, 2 or 3 years depending on the frequency of hemarthrosis during the year and the severity of joint damage primarily identified. Results. The results included both the improvement along with the stabilization of intra-state structures and the negative dynamic shifts. MRI showed that the reduction of bleeding in the joints on the background of hemostatic replacement therapy led to subsiding inflammation in the joints and significant decrease in the amount of intra-articular effusion (n = 11; p = 0.03, decrease in the number of joints with symptoms of bone marrow edema (n = 8, the absence of observations with negative changes in the form of increasing the thickness of the synovial membrane. Negative dynamics of joint condition presented as increasing of the depth and length of erosive process (n = 5; 22.7%, degenerative changes in ligaments and menisci (n = 2; 9% under the condition of regular administration of clotting factors was associated

One-electron spectrum of Xe VIII

International Nuclear Information System (INIS)

Roberts, J.R.; Knystautas, E.J.; Sugar, J.

1979-01-01

The spectrum of Xe VIII has been observed in a theta-pinch discharge. New line identifications were made that determine the energies of the 6s, 7s, 6p, and 5f terms relative to the 5s 2 S ground state and confirm the previously known 5p and 5d terms. An independent system of levels derived from the observed 4f-ng (n = 5,6) transitions was found. Its position relative to the ground state is obtained from a predicted value for the 5g effective quantum number n*. From the ns series (n=5--7) a value for the ionization enegy of 105.91 +- 0.05 eV was derived

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

... Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... 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...

Influence of Problem Based Learning on Critical Thinking Skills and Competence Class VIII SMPN 1 Gunuang Omeh, 2016/2017

Science.gov (United States)

Aswan, D. M.; Lufri, L.; Sumarmin, R.

2018-04-01

This research intends to determine the effect of Problem Based Learning models on students' critical thinking skills and competences. This study was a quasi-experimental research. The population of the study was the students of class VIII SMPN 1 Subdistrict Gunuang Omeh. Random sample selection is done by randomizing the class. Sample class that was chosen VIII3 as an experimental class given that treatment study based on problems and class VIII1 as control class that treatment usually given study. Instrument that used to consist of critical thinking test, cognitive tests, observation sheet of affective and psychomotor. Independent t-test and Mann Whitney U test was used for the analysis. Results showed that there was significant difference (sig competences.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

Science.gov (United States)

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Chaos in long-term behavior of some Bianchi-type VIII models

Energy Technology Data Exchange (ETDEWEB)

Halpern, P

1987-01-01

The long-term behavior of Bianchi-type VIII models with three different types of stress-energy tensors are examined and compared. The vacuum model, a matter-filled model, and a model with an electromagnetic field are considered. In each case the existence of chaotic behavior and transitions to chaotic behavior are discussed.

Factors Associated With Academic Performance Among Second-Year Undergraduate Occupational Therapy Students

OpenAIRE

Bonsaksen, Tore; Ellingham, Brian; Carstensen, Tove

2018-01-01

Background: Research into occupational therapy education and its outcomes for students is growing. More research is needed to determine the factors of importance for occupational therapy students’ academic outcomes. This study aimed to investigate factors associated with academic performance among second-year undergraduate occupational therapy students in Norway. Methods: Occupational therapy students (n = 111) from two education programs completed questionnaires asking for sociodemograph...

Enhanced glycosylation of factor VIII:C in capillary endothelial cells following β-adrenoreceptor stimulation is not due to increased sugar transport

International Nuclear Information System (INIS)

Tavarez-Pagan, J.J.; Oliveira, C.M.; Banerjee, D.K.

1990-01-01

Factor VIII:C (Antihemophilia Factor A) in capillary endothelial cells from bovine adrenal medulla found to contain M r 200,000 and M r 46,000 dalton protein species when analyzed by SDS-PAGE under reduced condition. But the secretory FVIII:C under non-reduced condition gave rise to a protein of M r 270,000 dalton indicating that the heavy and light chains are held together by S-S bridge. Upon stimulation of these cells with β-agonist, isoproterenol (10 -7 M), a 2-fold increase in the ratio of [ 3 H]-mannose to [ 35 S]-methionine incorporation in immunoprecipitated FVIII:C was observed. In order to understand the molecular mechanism of this increase, a detail study of sugar transport was carried out. The transport of 2-deoxy-D-[ 3 H]-glucose in these cells was time and temperature dependent. Furthermore, inhibition of 2-deoxy-D-[ 3 H]-glucose uptake by cytochalasin B strongly supported for a carrier mediated process. However, when the transport studies were conducted in the presence of isoproterenol at 10 -5 M or 10 -7 M or 8 Br-cAMP (2 mM) no increase was observed. The kinetic studies indicated that the K m and V max for 2 deoxy-D-[ 3 H]-glucose were 0.24 mM and 0.88 nmol/mg protein/minute, respectively under normal conditions but these values were changed to 0.37 mM and 0.69 nmol/mg protein/minute when stimulated with isoproterenol (10 -7 M)

Synthesis of dispersive iron or iron–silver nanoparticles on engineered capsid pVIII of M13 virus with electronegative terminal peptides

Energy Technology Data Exchange (ETDEWEB)

Zhang, Shuai; Nakano, Kazuhiko; Zhang, Shu-liang; Yu, Hui-min, E-mail: yuhm@tsinghua.edu.cn [Tsinghua University, Key Laboratory of Industrial Biocatalysis of the Ministry of Education, Department of Chemical Engineering (China)

2015-10-15

M13 is a filamentous Escherichia coli virus covered with five types of capsid proteins, in which pVIII with ∼2700 copies was around the cylindered surface and pIII with five copies located at one end of the phage particle. The pIII-engineered M13 phages with enhanced binding specificity toward Fe were screened after five rounds of biopanning, and the one containing ATPTVAMSLSPL peptide at pIII-terminus was selected for mediated synthesis of zero valent (ZV) Fe nanoparticles (NPs) with the wild M13 as control. Under a reducing environment, uniformly dispersed ZVFeNPs with diameter of 5–10 nm were both synthesized and the morphologies after annealing were confirmed to be face-centered cubic type. The synthesized FeNPs mediated by the two phages showed no significant difference, revealing that the pVIII capsid did dominant contribution to metal binding in comparison with the pIII. A novel pVIII-engineered M13 containing AAEEEDPAK at terminus, named as 4ED-pVIII-M13, was constructed and it carried one more negatively charged residue than the wild one (AEGDDPAK). Metal adsorption quantification showed that the binding affinity of the 4ED-pVIII-M13 toward Ag and Ni ions improved to 62 and 18 % from original 21 and 6 %, respectively. The binding affinity toward Fe remained constant (∼85 %). ZVFe–Ag bi-NPs were successfully synthesized through mediation of 4ED-pVIII-M13. Particularly, the Fe:Ag ratio in the bi-NPs was conveniently controlled through changing the molar concentration of FeCl{sub 2} and AgNO{sub 3} solution before reduction.

Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

Science.gov (United States)

Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

2015-04-09

Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. © 2015 by The American Society of Hematology.

The Effect of Growth Temperature and V/III Flux Ratio of MOCVD Antimony Based Semiconductors on Growth Rate and Surface Morphology

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Ramelan Ari Handono

2017-01-01

Full Text Available Epitaxial Alx Ga1-x Sb layers on GaSb and GaAs substrates have been grown by atmospheric pressure metalorganic chemical vapor deposition using TMAl, TMGa and TMSb. Nomarski microscope and a profiler were employed to examine the surface morphology and growth rate of the samples. We report the effect of growth temperature and V/III flux ratio on growth rate and surface morphology. Growth temperatures in the range of 520°C and 680°C and V/III ratios from 1 to 5 have been investigated. A growth rate activation energy of 0.73 eV was found. At low growth temperatures between 520 and 540°C, the surface morphology is poor due to antimonide precipitates associated with incomplete decomposition of the TMSb. For layers grown on GaAs at 580°C and 600°C with a V/III ratio of 3 a high quality surface morphology is typical, with a mirror-like surface and good composition control. It was found that a suitable growth temperature and V/III flux ratio was beneficial for producing good AlGaSb layers. Undoped AlGaSb grown at 580°C with a V/III flux ratio of 3 at the rate of 3.5 μm/hour shows p-type conductivity with smooth surface morphology

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: https://www.ias.ac.in/article/fulltext/jbsc/031/03/0309-0322 ...

Absorption signatures of warm-hot gas at low redshift : Ne VIII

NARCIS (Netherlands)

Tepper-García, T

2013-01-01

At z {lt} 1 a large fraction of the baryons is thought to reside in diffuse gas that has been shock-heated to high temperatures (10$^{5}$-10$^{6}$ K). Absorption by the 770.41, 780.32 å doublet of Ne VIII in quasar spectra represents a unique tool to study this elusive warm-hot phase. We have

Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

Indian Academy of Sciences (India)

In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the ... The self-bound state appears to be at ρ ... The observations suggest that the Hubble expansion of the Universe ... Taking motivation from.

PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

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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

Leonor Plantagenet y la consolidación castellana en el reinado de Alfonso VIII

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Cerda, José Manuel

2012-12-01

Full Text Available The kingdom of Castile experienced a process of political and territorial consolidation between the death of Sancho III in 1158 and the Curia of Carrión de los Condes in 1188, leaving behind the troublesome minority of Alfonso VIII and the subordination to the kingdom of Leon, and thus becoming a dominant power within the peninsula, and one that achieved considerable success in the Reconquest. The following article is part of a biographical approach to Eleanor Plantagenet, queen consort of Alfonso VIII, and by means of a specifi c focus offers an analysis of the role played by the English queen in this process of political consolidation of Castile. As we approach the eighth centenary of her death, the life and work of this little-studied woman emerges as a testimony to the important diplomatic and cultural tasks assumed by queens in twelfth-century Europe.

Desde la muerte de Sancho III en 1158 a la Curia de Carrión de los Condes en 1188, el reino castellano experimentó una consolidación política y territorial que dejó atrás la problemática minoría de Alfonso VIII y la subordinación al reino de León, que lo constituyó en un poder dominante dentro de la península y que logró un avance importante en la empresa reconquistadora. El presente trabajo es parte de un acercamiento biográfico a Leonor Plantagenet, consorte de Alfonso VIII, y que por medio de un enfoque particular ofrece un análisis de la incidencia que tuvo la reina inglesa en este proceso de afianzamiento político de Castilla. En las vísperas del octavo centenario de su muerte, la vida y obra de esta mujer hasta ahora poco estudiada, surge como un testimonio importante a la labor diplomática y cultural que asumían las reinas en la Europa del siglo XII.

VIII Brazilian Meeting on Simulational Physics (BMSP)

International Nuclear Information System (INIS)

Branco, N. S.; Figueiredo, W.; Plascak, J. A.; Santos, M.

2016-01-01

This special issue includes invited and selected articles of the VIII Brazilian Meeting on Simulational Physics (BMSP), held in Florianópolis, Santa Catarina, Brazil, from 3rd to 8th August, 2015. This is the eighth such meeting, and the second one to have contributed papers published in Journal of Physics: Conference Series (the other was the VII BMSP). The previous meetings in the BMSP series took place in the mountains of Minas Gerais, in the region of the Brazilian Pantanal, and in the shores of Paraíba. Now, for the first time, the Meeting was held in Florianópolis, with its pleasing shores, the capital of Santa Catarina state. The VIII BMSP brought together about 50 researchers from all over the world for a vibrant and productive conference. As in the previous meetings, the talks and posters highlighted recent advances in applications, algorithms, and implementation of computer simulation methods for the study of condensed matter, materials, and out of equilibrium, quantum and biologically motivated systems. We are sure that this meeting series will continue to be an important occasion for people working in simulational physics to exchange ideas and discuss the state of the art of this always expanding field. We are very glad to put together this special issue, and are most appreciative of the efforts of the editors of the Journal of Physics: Conference Series for making this publication possible. We are grateful for the outstanding work of the Florianopolis team, for the financial support of the Brazilian agencies CAPES and CNPq, and of the Federal Universities UFPB and UFSC. At last, but not least, we would like to acknowledge all of the authors for their written submissions. (paper)

A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

Science.gov (United States)

Coleman, Lewis S

2007-01-01

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

Structure and stability of hexa-aqua V(III) cations in vanadium redox flow battery electrolytes.

Science.gov (United States)

Vijayakumar, M; Li, Liyu; Nie, Zimin; Yang, Zhenguo; Hu, JianZhi

2012-08-07

The vanadium(III) cation structure in mixed acid based electrolyte solution from vanadium redox flow batteries is studied by (17)O and (35/37)Cl nuclear magnetic resonance (NMR) spectroscopy, electronic spectroscopy and density functional theory (DFT) based computational modelling. Both computational and experimental results reveal that the V(III) species can complex with counter anions (sulfate/chlorine) depending on the composition of its solvation sphere. By analyzing the powder precipitate it was found that the formation of sulfate complexed V(III) species is the crucial process in the precipitation reaction. The precipitation occurs through nucleation of neutral species formed through deprotonation and ion-pair formation process. However, the powder precipitate shows a multiphase nature which warrants multiple reaction pathways for precipitation reaction.

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.

VIII International Meeting on Lorentzian Geometry

CERN Document Server

Flores, José; Palomo, Francisco; GeLoMa 2016; Lorentzian geometry and related topics

2017-01-01

This volume contains a collection of research papers and useful surveys by experts in the field which provide a representative picture of the current status of this fascinating area. Based on contributions from the VIII International Meeting on Lorentzian Geometry, held at the University of Málaga, Spain, this volume covers topics such as distinguished (maximal, trapped, null, spacelike, constant mean curvature, umbilical...) submanifolds, causal completion of spacetimes, stationary regions and horizons in spacetimes, solitons in semi-Riemannian manifolds, relation between Lorentzian and Finslerian geometries and the oscillator spacetime. In the last decades Lorentzian geometry has experienced a significant impulse, which has transformed it from just a mathematical tool for general relativity to a consolidated branch of differential geometry, interesting in and of itself. Nowadays, this field provides a framework where many different mathematical techniques arise with applications to multiple parts of mathem...

Ramsay Hunt syndrome with unilateral polyneuropathy involving cranial nerves V, VII, VIII, and XII in a diabetic patient.

Science.gov (United States)

Sun, Wei-Lian; Yan, Jian-Liang; Chen, Li-Li

2011-01-01

Ramsay Hunt syndrome is a rare complication of the varicella zoster virus, defined as a peripheral facial palsy that typically results from involvement of the facial and auditory nerves. Ramsay Hunt syndrome can be associated with cranial nerves V, VI, IX, and X but rarely with XII. We describe an atypical case of Ramsay Hunt syndrome with multiple cranial nerve involvement of nerves V, VII, VIII, and XII. Antiviral drugs, antibiotics, insulin, and traditional Chinese drugs were administered immediately after admission. After 3 months of combination therapy, the patient had recovered satisfactorily. Herpes zoster can cause severe infections in diabetic patients and should be treated as soon after detection as possible. Ramsay Hunt syndrome should be recognized as a polycranial neuritis characterized by damage to sensory and motor nerves. In addition to facial and vestibular nerve paralysis, Ramsay Hunt syndrome may also involve cranial nerves V and XII.

Expressão citofotométrica dos marcadores tumorais CD-34 e fator VIII no câncer de cólon

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Cacilda Joyce Ferreira da Silva Garcia

Full Text Available OBJETIVOS: Verificar a posssibilidade de quantificar a expressão dos marcadores tumorais CD-34 e Fator VIII no câncer de cólon; verificar se existe superioridade entre um marcador e outro para estudo da angiogênese; verificar se há correlação na análise do índice de marcagem e a densidade óptica média nos marcadores utilizados. MÉTODOS: Dezessete casos de adenocarcinoma colorretal recuperados de blocos de parafina e confirmados pela hematoxilina-eosina, foram submetidos à coloração imunoistoquímica pelo método da estreptoavidina-biotina-peroxidase e utilizados os marcadores tumorais CD-34 e Fator VIII. Após este processo as lâminas foram submetidas à leitura no sistema Samba 4000® e avaliadas pelo software Immuno®. Os parâmetros estudados foram: índice de marcagem e densidade óptica, expressos por médias, medianas, valores mínimos, valores máximos e desvios-padrão, analisados estatisticamente. RESULTADOS: Para o marcador CD-34 não houve normalidade dos dados em relação ao índice de marcagem e houve para a densidade óptica. Para o Fator VIII, houve normalidade de dados em relação ao índice de marcagem e para a densidade óptica. CONCLUSÃO: Foi possível quantificar a expressão dos marcadores tumorais CD-34 e Fator VIII através do índice de marcagem e da densidade óptica média; não houve diferença entre os marcadores em relação à média do índice de marcagem e da densidade óptica, não sendo possível definir superioridade entre um e outro; não foi observada tendência à correlação quando comparados densidade óptica e índice de marcagem do Fator VIII e do CD-34 isoladamente estudados; não houve correlação entre o índice de marcagem do Fator VIII quando comparado com o CD-34, bem como a densidade óptica do Fator VIII com o CD-34.

Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

Indian Academy of Sciences (India)

In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the context of general relativity are explored. To obtain deterministic solution of the Einstein's field equations, various techniques are adopted. The features of the obtained solution are discussed.

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

2016-01-01

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. PMID:27381905

Keefektifan Experiential Learning Berbantuan Origami Terhadap Kemampuan Keruangan Siswa Kelas VIII

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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�

Risk factor management: antiatherogenic therapies.

Science.gov (United States)

Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

2009-08-01

Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

Occupational Therapy Practitioners with Occupational Musculoskeletal Injuries: Prevalence and Risk Factors.

Science.gov (United States)

Alnaser, Musaed Z

2015-12-01

The purpose of this study was to examine the prevalence and risk factors of occupational musculoskeletal injuries (OMIs) among occupational therapy practitioners over a 12-month period. A self-administered questionnaire mailed to 500 randomly selected practicing occupational therapists (OTs) and occupational therapy assistants (OTAs) living in the state of Texas. A response rate of 38 % was attained with 192 questionnaires returned. In a 12-months working period, 23 % of occupational therapy practitioners experienced musculoskeletal injuries. Muscle strain (52 %) was most reported injury and lower back (32 %) was most injured body part. Years of practicing experience (t = 2.83, p = 0.01), and age x(2)(2, N = 192) = 8.28, p = 0.02 were found as significant factors associated with injuries among OTAs. No factors were significantly associated with injuries among OTs. Patient handling was the primary factor associated with injuries. Also, minimal experience and older age were concluded as risk factors that might contribute to OMIs.

Neurotology findings in patients with diagnosis of vascular loop of cranial nerves VIII in magnetic resonance imaging

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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.

Analysis of the factors motivating HCV-infected patients to accept interferon therapy

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Nagao Yumiko

2012-08-01

Full Text Available Abstract Background The aims of this study were to analyze factors motivating the acceptance of interferon (IFN therapy and to clarify the prevalence of oral mucosal diseases in hepatitis C virus (HCV-infected Japanese patients treated with IFN. Findings A total of 94 HCV-infected patients who were admitted to our hospital for IFN therapy were asked questions regarding their motivation to accept IFN therapy and were investigated for the presence of oral lichen planus (OLP before and during IFN treatment. Recommendation and encouragement from other people were the most common factors motivating the acceptance of IFN therapy (49/94, 52.13%. The other motivators were independent decision (30.85%, economic reasons (5.32%, and others. According to multivariate analysis, three factors – sex (male, retreatment after previous IFN therapy, and independent decision to accept IFN therapy - were associated with patients after curative treatment of hepatocellular carcinoma (HCC. The adjusted odds ratios for these three factors were 26.06, 14.17, and 8.72, respectively. The most common oral mucosal lesions included OLP in 11 cases (11.70%. One patient with OLP had postoperative squamous cell carcinoma of the tongue. The rate of sustained virological response (SVR was 45.45% in cases with OLP and 54.55% in cases without OLP. There were no patients who discontinued IFN therapy because of side effects such as oral mucosal diseases. Conclusions We should give full explanation and recommend a course of treatment for a patient to accept IFN therapy. The system to support liver disease as well as oral diseases is also necessary for patient treated for IFN therapy.

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

Science.gov (United States)

Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

2012-07-05

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

Penggunaan Media Presentase Microsoft Power Point Untuk Meningkatkan Hasil Belajar IPS Terpadu Pada Siswa Kelas VIII a SMP Negeri 2 Tanantovea

OpenAIRE

Hitler, Ahmad

2014-01-01

Permasalahan yang diangkat dalam penelitian adalah apakah dengan penggunaan media Presentase Microsoft Power Point pada mata pembelajaran IPS Terpadu dapat meningkatkan hasil belajar siswa kelas VIII A di SMP Negeri 2 Tanantovea. Penelitian ini bertujuan untuk meningkatkan hasil belajar siswa pada pokok bahasan Kolonialisme dan Imperialisme Barat di kelas VIII A SMP Negeri 2 Tanantovea. Penelitian ini dilakukan dalam 2 siklus, setiap siklus terdiri dari perencanaan, pelaksanaan tindakan, obs...

Gene therapy with growth factors for periodontal tissue engineering–A review

Science.gov (United States)

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

Pengembangan Perangkat Pembelajaran Matematika Berbasis Problem Based Learning (PBL untuk Meningkatkan Kemampuan Pemecahan Masalah Peserta Didik Kelas VIII

Directory of Open Access Journals (Sweden)

Rizza Yustianingsih

2017-09-01

Full Text Available Abstrak. Berdasarkan hasil penelitian pendahuluan pada kelas VIII SMP di lapangan, masih ditemukan kemampuan pemecahan masalah matematis siswa dalam masalah nyata yang belum optimal dan aktivitas siswa tidak mendukung proses belajar mereka. Salah satu faktornya adalah tidak cocoknya perangkat pembelajaran yang dapat memudahkan pembelajar untuk memperbaiki pemecahan kemampuan matematika dan kemampuan belajar siswa. Dari situ, untuk mendasari melakukan pengembangan perangkat pembelajaran matematika, ada rencana rencana pembelajaran (RPP dan lembar kerja siswa (LKPD berbasis Problem Based Learning (PBL, yang dapat memberikan pengalaman belajar untuk belajar pemecahan masalah dan dapat memberikan efek potensial yang baik pada aktivitas siswa selama proses belajar. Data dikumpulkan melalui observasi, kuesioner, wawancara, dan uji kemampuan pemecahan masalah. Subyek penelitian ini adalah siswa kelas VIII SMP N 3 Sawahlunto. Pengembangan penelitian ini yang digunakan adalah mode Plomp yang terdiri dari tahap awal penelitian, tahap prototipe, dan tahap penilaian. Berdasarkan hasil analisis data, terlihat bahwa alat pembelajaran berdasarkan PBL telah memenuhi kriteria yang valid dalam hal isi dan konstruksi. Peralatan pelajaran telah dianggap praktis dalam hal pelaksanaan dan efisiensi penggunaan waktu oleh guru dan siswa. Alat pelajaran juga efektif dalam hal proses penguasaan presentasi siswa belajar setelah menggunakan pembelajaran berbasis perangkat berbasis pembelajaran lebih besar dari atau sama dengan 75% sedangkan dalam hal hasil rata-rata siswa telah aktif dalam belajar. Kata kunci: Perangkat Pelajaran Matematika, Pemecahan Masalah, PBL.   Abstract. Based on the results of preliminary studies at grade VIII SMP in the field, it is still  found a mathematical problem solving ability of students in real problem who have not optimally and students activities do not support their learning process. One of the  factor is unsuitable of learning tools

Significantly improved surface morphology of N-polar GaN film grown on SiC substrate by the optimization of V/III ratio

Science.gov (United States)

Deng, Gaoqiang; Zhang, Yuantao; Yu, Ye; Yan, Long; Li, Pengchong; Han, Xu; Chen, Liang; Zhao, Degang; Du, Guotong

2018-04-01

In this paper, N-polar GaN films with different V/III ratios were grown on vicinal C-face SiC substrates by metalorganic chemical vapor deposition. During the growth of N-polar GaN film, the V/III ratio was controlled by adjusting the molar flow rate of ammonia while keeping the trimethylgallium flow rate unchanged. The influence of the V/III ratio on the surface morphology of N-polar GaN film has been studied. We find that the surface root mean square roughness of N-polar GaN film over an area of 20 × 20 μm2 can be reduced from 8.13 to 2.78 nm by optimization of the V/III ratio. Then, using the same growth conditions, N-polar InGaN/GaN multiple quantum wells (MQWs) light-emitting diodes (LEDs) were grown on the rough and the smooth N-polar GaN templates, respectively. Compared with the LED grown on the rough N-polar GaN template, dramatically improved interface sharpness and luminescence uniformity of the InGaN/GaN MQWs are achieved for the LED grown on the smooth N-polar GaN template.

Life-threatening hemorrhage from acquired hemophilia A as a presenting manifestation of prostate cancer

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Chirag Sheth

2016-09-01

Full Text Available Acquired factor VIII deficiency (acquired hemophilia A is a rare condition characterized by the acquisition of autoantibodies that affect the clotting activity of factor VIII (fVIII. The most common manifestation in affected patients is a hemorrhagic diathesis. This disorder is associated with autoimmune diseases, pregnancy, postpartum period, drugs, and malignancy. Management of this condition begins with attempts to arrest an acute bleed based on the site and severity of bleeding and inhibitor titer. The next priority is eradication of the fVIII antibodies using immunosuppressive therapies. We report the case of a 66-year-old male who presented with spontaneous right thigh hematoma with prolonged activated partial prothrombin time and normal prothrombin time. Mixing studies confirmed the presence of an inhibitor. Further investigation for the underlying etiology of acquired hemophilia A leads to diagnosis of prostate cancer. Treatment consisted of bypassing agents including activated factor VII and activated prothrombin plasma concentrate to arrest the bleeding. Steroids and cyclophosphamide were added to suppress the fVIII inhibitors. Concomitant treatment of locally advanced prostate cancer with chemotherapy confirmed the eradication of the inhibitors. To our knowledge, this is the first reported case of prostate cancer diagnosed and treated simultaneously with acquired hemophilia A resulting in favorable patient outcome.

Synthesization of the Ar VIII 3s-3p beam-foil decay curve

International Nuclear Information System (INIS)

Lindgaard, A.; Veje, E.

1981-01-01

The beam-foil decay curve for the 3s-3p transition in Ar VIII has been simulated from experimentally determined relative initial level populations and transition probabilities calculated in the numerical Coulomb approximation. Good agreement is observed between simulated and measured decay curves. A discussion of the simulation is given. (Auth.)

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.

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

Science.gov (United States)

de Moerloose, P; Schved, J-F; Nugent, D

2016-07-01

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor

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Virginia J. Savin

2017-01-01

Full Text Available A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1 as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1 and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.

Dose modification factors in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Allen, B.J. (Australian Nuclear Science and Technology Organization (ANSTO), Menai (Australia))

1993-01-01

The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. (orig.).

Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

Energy Technology Data Exchange (ETDEWEB)

Barth, Rolf F. E-mail: barth.1@osu.edu; Wu Gong; Yang Weilian; Binns, Peter J.; Riley, Kent J.; Patel, Hemant; Coderre, Jeffrey A.; Tjarks, Werner; Bandyopadhyaya, A.K.; Thirumamagal, B.T.S.; Ciesielski, Michael J.; Fenstermaker, Robert A

2004-11-01

Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B{sub 1100}), the mean boron concentration in rats bearing either F98{sub EGFR} or F98{sub WT} gliomas were 92.3{+-}23.3 {mu}g/g and 36.5{+-}18.8 {mu}g/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B{sub 1000}) was 6.7{+-}3.6 {mu}g/g. Based on its favorable in vivo uptake, C225-G5-B{sub 1100} was evaluated as a delivery agent for BNCT in F98{sub EGFR} glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B{sub 1100}, administered by convection enhanced delivery (CED), was 45{+-}3 d compared to 25{+-}3 d for untreated control animals. A further enhancement in MST to >59 d was obtained by administering C225-G5-B{sub 1100} in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.

Influence Model Assisted Learning Cycle Mind Map to Achievement Physics Laboratory Judging from the performance Grade VIII SMPN 1 Rejoso Pasuruan

OpenAIRE

Ary Analisa Rahma

2014-01-01

Pengaruh Model Siklus Belajar Berbantuan Mind Map terhadap Prestasi Belajar Fisika Ditinjau dari Kinerja Laboratorium Siswa Kelas VIII SMPN 1 Rejoso Kabupaten Pasuruan Abstract: This study aimed to examine the effect of the learning cycle models aided the mind map on the learning achievement in terms of the performance of laboratory physics class VIII student on light material in SMP Negeri 1 Rejoso Pasuruan. This study is a quasi-experimental research. The research design used is a 2 x 2...

Ergonomic factors that cause the presence of pain muscle in students of dentistry

OpenAIRE

Díaz Caballero, Antonio José; Gomez Palencia, Isabel Patricia; Díaz Cárdenas, Shyrley

2010-01-01

Objective: To identify the ergonomic factors and the presence of muscular pain in dental students of VIII, IX, X semesters presently practicing at the clinics of the College of Dentistry of university of Cartagena, Colombia, South America. Materials and methods: This is a descriptive study carried out in dental students of the VIII, IX, and X semesters which were undergoing clinical practice at the College of Dentistry of University of Cartagena. A convenience sample of 83 students who m...

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.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

Science.gov (United States)

Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B

2016-01-01

Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355

Efeitos de humor no poema VIII de Catulo

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Paulo Sérgio Vasconcellos

1997-12-01

Full Text Available Neste artigo apresenta-se uma contribuição ao estudo dos efeitos de humor no poema VIII de Catulo; de fato, além do metro dessa composição e de outros elementos criadores de distanciamento irônico que os estudiosos têm apontado, um outro aspecto de sua forma, ainda pouco percebido, guia a leitura para essa interpretação: o jogo, a maneira de anagrama imperfeito (o “hipograma”, ou, mais precisamente, “criptograma”, de Saussure, com os sons do nome da amada, aparentemente calado. E mais uma das maneiras com que o poeta elabora a jocosa diferença entre o que se diz e o que, sentido e reprimido, deixa-se, porém, transparecer.

Placental growth factor expression is reversed by antivascular endothelial growth factor therapy under hypoxic conditions.

Science.gov (United States)

Zhou, Ai-Yi; Bai, Yu-Jing; Zhao, Min; Yu, Wen-Zhen; Huang, Lv-Zhen; Li, Xiao-Xin

2014-08-01

Clinical trials have revealed that the antivascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF. CoCl2-induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies. PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05). The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.

Factors related to pain during routine photodynamic therapy

DEFF Research Database (Denmark)

Miller, I M; Nielsen, J S; Lophaven, S

2011-01-01

between pain-reducing intervention and diagnosis, pre-treatment, gender or age was found. CONCLUSIONS: Pain-reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp......BACKGROUND: Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain-intervention during routine PDT therapy are poorly described. OBJECTIVES: To describe the consequences of pain during PDT by describing the use of pain......-reducing interventions in routine use. We studied the frequency as well as level of pain-reducing intervention. METHODS: Descriptive data from PDT treated patients. The level of pain-reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block. RESULTS: Data from 983 PDT...

Anterior Inferior Cerebellar Arteries Juxtaposed with the Internal Acoustic Meatus and Their Relationship to the Cranial Nerve VII/VIII Complex.

Science.gov (United States)

Alonso, Fernando; Kassem, Mohammad W; Iwanaga, Joe; Oskouian, Rod J; Loukas, Marios; Demerdash, Amin; Tubbs, R Shane

2017-08-16

Vascular loops in the cerebellopontine angle (CPA) and their relationship to cranial nerves have been used to explain neurological symptoms. The anterior inferior cerebellar artery (AICA) has variable branches producing vascular loops that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can lead to various clinical presentations, including hemifacial spasm (HFS), tinnitus, and hemiataxia. The formation of arterial loops inside or outside of the internal auditory meatus (IAM) can cause abutment or compression of CN VII and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of the cerebellopontine angle in the supine position. In regard to relationships between the AICA and the nerves of the facial/vestibulocochlear complex, 33 arteries (66%) traveled in a plane between the facial/nervus intermedius nerves and the cochlear and vestibular nerves. Five arteries (10%) traveled below the CN VII/VIII complex, six (12%) traveled posterior to the nerve complex, four (8%) formed a semi-circle around the upper half of the nerve complex, and two (4%) traveled between and partially separated the nervus intermedius and facial nerve proper. Our study found that the majority of AICA will travel in a plane between the facial/nervus intermedius nerves and the cochlear and vestibular nerves. Although the relationship between the AICA and porus acusticus and AICA and the nerves of the CN VII/VIII complex are variable, based on our findings, some themes exist. Surgeons should consider these with approaches to the cerebellopontine angle.

Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old man: a case report

Directory of Open Access Journals (Sweden)

Blanchard Elizabeth

2010-07-01

Full Text Available Abstract Introduction Acquired factor VIII deficiency is a rare entity that can lead to severe and life-threatening bleeding. We describe a case of severe bleeding from the tongue secondary to acquired hemophilia and discuss treatment options, including aminocaproic acid and recombinant factor VIII, which have not been widely reported in the literature for the management of such patients. Case presentation A 94-year-old Caucasian man presented to our institution with diffuse bruising and extensive bleeding from the tongue secondary to mechanical trauma. He had no prior history of bleeding and his medical history was unremarkable except for dementia and hypertension. Coagulation studies revealed a prolonged activated partial thromboplastin time and a mixing study was consistent with the presence of an inhibitor. Quantitative assays revealed a reduced level of factor VIII activity (1% and the presence of a factor VIII inhibitor, measured at seven Bethesda units, in the serum. Oral prednisone therapy (60mg/day was given. He also received intravenous aminocaproic acid and human concentrate of factor VIII (Humate-P and topical anti-thrombolytic agents (100 units of topical thrombin cream. His hospital course was prolonged because of persistent bleeding and the development of profuse melena. He required eight units of packed red blood cells for transfusion. Hospitalization was also complicated by bradycardia of unclear etiology, which started after infusion of aminocaproic acid. His activated partial thromboplastin time gradually normalized. He was discharged to a rehabilitation facility three weeks later with improving symptoms, stable hematocrit and resolving bruises. Conclusions Clinicians should suspect a diagnosis of acquired hemophilia in older patients with unexplained persistent and profound bleeding from uncommon soft tissues, including the tongue. Use of factor VIII (Humate-P and aminocaproic acid can be useful in this coagulopathy but

Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

Science.gov (United States)

Livnat, Tami; Zivelin, Ariella; Tamarin, Ilia; Guetta, Victor; Salomon, Ophira

2009-12-01

Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.

Factors associated with therapy noncompliance in type-2 diabetes patients

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Hernández-Ronquillo Lizbeth

2003-01-01

Full Text Available OBJECTIVE: To identify the frequency and factors associated with therapy noncompliance in type-2 diabetes mellitus patients. MATERIAL AND METHODS: A cross-sectional study was carried out in 79 patients with type-2 diabetes mellitus seen in major hospitals of Mexico City. Patients were visited at home, from March 1998 to August 1999, to measure compliance with prescribed therapy. Complying patients were defined as those taking at least 80% of their pills or 80% of their corresponding insulin dose. The degree of compliance with therapy components (diet, amount of exercise, and keeping appointments was measured. RESULTS: The average age of study subjects was 59 years (SD 11 years; 73% (n=58 were female subjects. The overall frequency of noncompliance was 39%. Noncompliance rates were: 62% for dietary recommendations, 85% for exercise, 17% for intake of oral hypoglycemic medication, 13% for insulin application, and 3% for appointment keeping. Hypertension plus obesity was the only factor significantly associated with noncompliance (OR 4.58, CI 95% 1.0, 22.4, p=0.02. CONCLUSIONS: The frequency of therapy noncompliance was very high, especially for diet and exercise.

Factor VIII (F8) inversions in severe hemophilia A: Male germ cell origin and diagnosis with RT-PCR

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Antonarakis, S.E. [Geneva Medical School (Switzerland)]|[Johns Hopkins School of Medicine, Baltimore, MD (United States); Rossiter, J.P. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Young, M. [Geneva Medical School (Switzerland)] [and others

1994-09-01

The Factor VIII (F8) gene, which is defective in hemophilia A, is located in the most telomeric megabase of Xq. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of the cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that therefore the event originates predominantly in male germ cells. In all 21 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis using markers within or very closely linked to F8, determined that it occurred in the male germline. In addition, all but one of 56 mothers of sporadic cases due to inversions were carriers. The data indicate that the F8 gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells. The mean age of maternal grandfathers at the birth of their carrier daughters was 29.9 years (13 cases), i.e. not different from the mean paternal age in the general population, supporting the hypothesis that the inversions occur in meiosis. The inversions can be diagnosed by Southern blot analysis. For more rapid diagnosis we have used RT-PCR of RNA ectopically expressed in blood. Oligonucleotides were used to PCR amplify, after the initial RT reaction of RNA samples using random hexamers, either the normal transcript (F8 exons 21 to 24;312 bp product) or the novel abnormal transcript that is generated after the inversion. Both type 1 and 2 inversions can be recognized in affecteds and carriers by the presence of the diagnostic PcR product of 248 bp. Correct diagnoses were made in samples from 6 patients and 2 carriers with type 1 inversions, 2 patients and 2 carriers with type 2 inversions and 5 normal controls.

Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

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Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))

1993-04-01

The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

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Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

Myelofibrosis and acquired hemophilia A: a case report.

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Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

PENGARUH PENGUASAAN KONSEP TEOREMA PYTHAGORAS TERHADAP KEMAMPUAN MENYELESAIKAN SOAL-SOAL BANGUN RUANG SISI DATAR PADA SISWA KELAS VIII MTS NEGERI BALANG-BALANG

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Syahrida Zaerani

2017-12-01

Abstract: This study aims to determine the impact of the mastery of Pythagoras Theorem concepts on the ability of MTs Negeri Balang-Balang grade VIII students to solve polyhedron problems. This study is a quantitative research with ex post facto design. Statistical population consists of all grade VIII students in MTs Negeri Balang-Balang which was 204 students. The number of sampling used is 102 respondents taken by simple random sampling technique. The research instrument was a test related to Pythagorean an polyhedron problems. Descriptive and inferential statistics were performed as the statistical analysis. The descriptive analysis result shows that the mastery of Pythagoras Theorem concepts is within the category of ‘high’ and the ability of solving polyhedron problems is as well. The inferential statistical analysis using simple linear regression shows that there is an impact of the mastery of Pythagoras Theorem concepts on polyhedron problem solving ability of Grade VIII students of MTs Negeri Balang-Balang.

[Survey of studies on time factor in acupoint sticking therapy for the bronchial asthma].

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Huang, Dong-e; Guo, Jian-hong; Lin, Ying

2010-02-01

Based on the retrieval of literatures in recent fifteen years, the time factors in the acupoint sticking therapy for the bronchial asthma are analyzed and compared in terms of the stage classification of patients, timing selection of acupoint sticking therapy and medication application, and times of application. The acupoint sticking therapy is mostly practiced during remittent stage of bronchial asthma; the timing selection is mostly during the hottest period of summer, the timing selection in certain cases is the coldest period of winter or any day; the duration of medication application is not consistent; therefore, the effectiveness of these cases is different. It may be that the ef fectiveness is proportional to the times and courses of acupoint sticking therapy for the bronchial asthma. In the future, the scientific designs which involve time factor are needed to elucidate the importance of time factor in acupoint sticking therapy for the bronchial asthma.

Progress and challenges in the development of a cell-based therapy for hemophilia A.

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Fomin, M E; Togarrati, P P; Muench, M O

2014-12-01

Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells. © 2014 International Society on Thrombosis and Haemostasis.

Progress and challenges in the development of a cell-based therapy for hemophilia A

Science.gov (United States)

Fomin, Marina E.; Togarrati, Padma Priya; Muench, Marcus O.

2015-01-01

Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review we discuss the possibilities, progress and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells (iPSCs) that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific iPSCs. PMID:25297648

Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

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Favaloro, Emmanuel J

2016-05-01

von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

Clinical factors affecting the outcome in postradioactive iodine (RAI) therapy patients - Philippine Heart Center experience

International Nuclear Information System (INIS)

Quinon, A.; Oabel, E.; Jimeno, C.

2007-01-01

Full text: Clinical factors such as patient's age, duration of the underlying autoimmune thyroid stimulus and anti-thyroid drug therapy may affect the outcome of patients who underwent RAI therapy. Objective: To evaluate the clinical factors affecting the outcome of RAI therapy. Methodology: Patients (n=41) with Graves' disease treated with anti-thyroid drugs were followed up after Radioactive Iodine therapy treatment. Thyroid scan, 2 and 24 hours radioactive iodine uptake were taken to compute for the therapy dose (120 uci) (computed thyroid weight in gms) (24-hour I 131 uptake). Patients were then divided into groups (Group 1= hypothyroid, Group 2= euthyroid, Group 3 hyperthyroid) based on their thyroid function results (FT3, FT4, TSH) after 2, 4, 6, 12 months post-therapy. Clinical and physiologic factors were then correlated with the outcome. Results: The population consisted of 41 patients (male=8, female=33) with an overall incidence of Group 1= 17%, Group 2= 54% and Group 3= 29% posttherapy. Factors such as age, with their means (Groups 134, 2= 39, 3=39 p= 0.42) and gland uptake (24-hour Groups 1= 53, 2= 61 358, p= 0.41) were not associated with the remission rate. Other factors that were related to the length of the disease such as duration of symptoms (Groups 121, 2=24, 3= 29 months p0.68), duration of medicine prior to RAI therapy (Group 1= 10, 2= 15, 3= 18 months p=0.306) and gland weight (Groups 1=40 2=42 3=46 grams p=0.78) tends to have a higher mean values in therapy failure patients. Conclusion: Clinical factors studied showed no significant differences among patients developing hypothyroid, euthyroid or hyperthyroid state. The data suggested that treatment failures in patients with Graves' disease could be improved by lessening the time interval between the diagnosis and radioactive iodine therapy. (author)

Non-genetic risk factors in haemophilia A inhibitor management - the danger theory and the use of animal models.

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Lövgren, K M; Søndergaard, H; Skov, S; Wiinberg, B

2016-09-01

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 genetic and therapy related risk factors. Many therapy-related risk factors have proven difficult to confirm due to several confounding factors and the small study populations available. However, clinical studies indicate that e.g. on-demand treatment and surgery affect inhibitor development, 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 stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass unnoticed. This role of danger in HA inhibitor formation has previously been suggested, but a thorough discussion of this subject is lacking. The present review will discuss the potential role of danger signals in haemophilia and inhibitor development, with focus on treatment related risk factors with a suspected danger signal aetiology; on-demand treatment, treatment during major bleeds or surgery, and treatment during infection or vaccination. Clinical studies as well as animal experiments addressing these factors will be reviewed. © 2016 John Wiley & Sons Ltd.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

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Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

2009-11-14

To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (Pfactors, factor IX and factor XI showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in

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.

Prospects and Challenges of Implementing the Hydrographic Region VIII Basin Plan

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Nathalia Silva Duarte

2011-12-01

Full Text Available The current “National Water Law” states that water resources plans must be elaborated by basins, states, and for the country. This essay discusses the water management process considering federal and state legislations and their interrelations, for the purpose of elucidating the gaps found in them , aiming at their applicability to the system of water resources management within the CBH- Macaé and Ostras scope. It also discusses the construction and evolution process of the above-mentioned committee, and developments in the implementation of the Basin Plan of Hydrographic Region VIII.

Influence of V/III growth flux ratio on trap states in m-plane GaN grown by ammonia-based molecular beam epitaxy

International Nuclear Information System (INIS)

Zhang, Z.; Arehart, A. R.; Hurni, C. A.; Speck, J. S.; Ringel, S. A.

2012-01-01

Deep level transient spectroscopy (DLTS) and deep level optical spectroscopy (DLOS) were utilized to investigate the behavior of deep states in m-plane, n-type GaN grown by ammonia-based molecular beam epitaxy (NH 3 -MBE) as a function of systematically varied V/III growth flux ratios. Levels were detected at E C - 0.14 eV, E C - 0.21 eV, E C - 0.26 eV, E C - 0.62 eV, E C - 0.67 eV, E C - 2.65 eV, and E C - 3.31 eV, with the concentrations of several traps exhibiting systematic dependencies on V/III ratio. The DLTS spectra are dominated by traps at E C - 0.14 eV and E C - 0.67 eV, whose concentrations decreased monotonically with increasing V/III ratio and decreasing oxygen impurity concentration, and by a trap at E C - 0.21 eV that revealed no dependence of its concentration on growth conditions, suggestive of different physical origins. Higher concentrations of deeper trap states detected by DLOS with activation energies of E C - 2.65 eV and E C - 3.31 eV in each sample did not display measureable sensitivity to the intentionally varied V/III ratio, necessitating further study on reducing these deep traps through growth optimization for maximizing material quality of NH 3 -MBE grown m-plane GaN.

Reduction of Risk Factors in Patients with Behavioral Dysphonia After Vocal Group Therapy.

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Silva, Wégina Jordâna Nascimento da; Lopes, Leonardo Wanderley; Macedo, Anny Elizabety Ramalho de; Costa, Denise Batista da; Almeida, Anna Alice Figueiredo de

2017-01-01

The origin and development of dysphonia, particularly behavioral dysphonia, is associated with several risk factors. Here, we verified the effectiveness of group therapy in reducing the risk factors, and established the association between risk factors and sex, age, profession, and diagnosis of laryngeal disorders in patients with behavioral dysphonia. This is a descriptive, quantitative, field intervention study. Participants (n = 26, adult patients of both sexes), with a diagnosis of behavioral dysphonia, received group therapy intervention. Data for risk factors were collected pre- and posttherapy using the Vocal Screening Protocol. The data were analyzed using descriptive and inferential statistics (Student t test, chi-squared test or Spearman correlation test). The majority (80.8%, n = 21) of patients were female, 65.4% (n = 17) were not in a vocal profession, and 42.3% (n = 11) presented with a lesion in the membranous portion of the vocal fold. The number of personal risk factors decreased after group therapy (P = 0.04). In addition, age was correlated with total (P = 0.001), environmental (P = 0.002), and personal (P = 0.003) vocal risk factors posttherapy. This study revealed an association between the reduction of personal risk factors and vocal group therapy, and a correlation between age and total, environmental, and personal vocal risk factors posttherapy. Thus, maintenance and origins of the behaviors that modify the behavioral aspects of the participants directly influence the production of individual vocal habits. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates.

Science.gov (United States)

Stidl, R; Fuchs, S; Bossard, M; Siekmann, J; Turecek, P L; Putz, M

2016-01-01

BAX 855 is a PEGylated human full-length recombinant factor VIII (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has been optimized to retain functionality of the FVIII molecule, improve its pharmacokinetic properties and allow less frequent injections while maintaining efficacy. The aim of this study was to confirm that the excellent safety profile of ADVATE remains unchanged after PEGylation. Non-clinical safety studies with BAX 855 and its respective unbound polyethylene glycol (PEG) were conducted in several species. The distribution of a single dose of radiolabelled BAX 855 was further investigated in rats. Publically available safety data on PEG alone and PEGylated biomolecules were summarized and reviewed for specific safety findings attributable to PEG or PEGylated biopharmaceuticals. Safety pharmacology studies in rabbits and macaques and repeated dose toxicity studies in rats and macaques identified no safety issues. Results of a distribution study in rats administered radiolabelled BAX 855 showed that radioactivity was completely excreted; urine was the major elimination route. A 28-day study in rats dosed with the unbound PEG constituent (PEG2ru20KCOOH) of BAX 855 showed no adverse or non-adverse effects. Safety data for PEG and PEG-protein conjugates indicate no safety concerns associated with PEG at clinically relevant dose levels. Although vacuolation of certain cell types has been reported in mammals, no such vacuolation was observed with BAX 855 or with the unbound PEG constituent. Non-clinical safety evaluation of PEG and BAX 855 identified no safety signals; the compound is now in clinical development for the treatment of patients with haemophilia A. © 2015 Baxalta Innovations GmbH. Haemophilia Published by John Wiley & Sons Ltd.

Current options and new developments in the treatment of haemophilia.

Science.gov (United States)

Wong, Trisha; Recht, Michael

2011-02-12

Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

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Allison M Lytle

2016-01-01

Full Text Available Immune responses to coagulation factors VIII (FVIII and IX (FIX represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.

Structural Mimics of the [Fe]-Hydrogenase: A Complete Set for Group VIII Metals.

Science.gov (United States)

Barik, Chandan Kr; Ganguly, Rakesh; Li, Yongxin; Leong, Weng Kee

2018-06-18

A set of structural mimics of the [Fe]-hydrogenase active site comprising all the group VIII metals, viz., [M(2-NHC(O)C 5 H 4 N)(CO) 2 (2-S-C 5 H 4 N)], has been synthesized. They exist as a mixture of isomers in solution, and the relative stability of the isomers depends on the nature of the metal and the substituent at the 6-position of the pyridine ligand.

Continuous infusion in haemophilia: current practice in Europe

NARCIS (Netherlands)

Batorova, A.; Holme, P.; Gringeri, A.; Richards, M.; Hermans, C.; Altisent, C.; Lopez-Fernández, M.; Fijnvandraat, K.

2012-01-01

. Continuous infusion (CI) of factor VIII (FVIII) is an effective method for replacement therapy in haemophilia. Recently, concerns have been raised regarding association of CI with the development of inhibitors. The aim of this study was to gain information on the current practices in Europe

Thirty years of hemophilia treatment in the Netherlands, 1972-2001

NARCIS (Netherlands)

Plug, Iris; van der Bom, Johanna G.; Peters, Marjolein; Mauser-Bunschoten, Evelien P.; de Goede-Bolder, Arja; Heijnen, Lily; Smit, Cees; Zwart-van Rijkom, Jeannette E. F.; Willemse, José; Rosendaal, Frits R.

2004-01-01

Since the introduction of replacement therapy in the early 1960s by the infusion of plasma-derived factor VIII and IX preparations, important changes have occurred for hemophilia patients. We studied the medical and social developments over 30 years of hemophilia treatment. Since 1972, 5

Predicting and influencing voice therapy adherence using social-cognitive factors and mobile video.

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van Leer, Eva; Connor, Nadine P

2015-05-01

Patient adherence to voice therapy is an established challenge. The purpose of this study was (a) to examine whether adherence to treatment could be predicted from three social-cognitive factors measured at treatment onset: self-efficacy, goal commitment, and the therapeutic alliance, and (b) to test whether the provision of clinician, self-, and peer model mobile treatment videos on MP4 players would influence the same triad of social cognitive factors and the adherence behavior of patients. Forty adults with adducted hyperfunction with and without benign lesions were prospectively randomized to either 4 sessions of voice therapy enhanced by MP4 support or without MP4 support. Adherence between sessions was assessed through self-report. Social cognitive factors and voice outcomes were assessed at the beginning and end of therapy. Utility of MP4 support was assessed via interviews. Self-efficacy and the therapeutic alliance predicted a significant amount of adherence variance. MP4 support significantly increased generalization, self-efficacy for generalization, and the therapeutic alliance. An interaction effect demonstrated that MP4 support was particularly effective for patients who started therapy with poor self-efficacy for generalization. Adherence may be predicted and influenced via social-cognitive means. Mobile technology can extend therapy to extraclinical settings.

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

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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

Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

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Karl C Desch

2018-01-01

Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

Uptake of isoniazid preventive therapy and its associated factors ...

African Journals Online (AJOL)

Background: Isoniazid Preventive Therapy (IPT) is an effective intervention for prevention of tuberculosis (TB) among HIV positive patients, and its use is recommended by the World Health Organization (WHO). Unfortunately the uptake of IPT in Kenya remains low (33%-40%) with limited knowledge on the factors that affect ...

Visualizing the Life and Legacy of Henry VIII: Guiding Students with Eight Types of Graphic Organizers

Science.gov (United States)

Gallavan, Nancy P.; Kottler, Ellen

2010-01-01

Delving into the life and legacy of Henry VIII is both complex and captivating. People seem compelled to learn more abut his critical contributions and controversial conduct that range from the significant to the scandalous. Reflecting on the history of the world would be incomplete without investigating the events and escapades associated with…

The physician's role in selecting a factor replacement therapy.

Science.gov (United States)

Pipe, S W

2006-03-01

Over the past 20 years, transmissions of human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma-derived or recombinant therapy in the USA, a record that can be largely attributed to the use of effective screening and inactivation technologies for known pathogens. The next significant threat will likely come from the emergence of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid-enveloped virus or prion, for which current inactivation methods are ineffective. Following the HIV crisis of the 1980s, government, patient advocacy groups, medical and scientific communities and the manufacturers of clotting therapies can learn from the past and approach potential threats from emerging pathogens in a proactive and productive manner. For clinicians, this includes actively engaging patients in a dialogue about all the factors that may influence their choice of clotting factor therapies, including emerging pathogens, patient convenience, consistency and reliability of supply, relative cost/benefit ratios, reimbursement issues (where applicable), patient preference and brand loyalty. It is our obligation as healthcare providers to understand potential risks and help make proactive decisions with our patients, decisions that often must be made in an environment of scientific uncertainty. Threats from infectious agents that were once deemed theoretical can, and often do, ultimately become real, with serious implications for morbidity and mortality.

Cerebral Vein Thrombosis:Screening of Acquired and Hereditary Thrombophilic Risk Factors

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Sarraf Payam

2009-10-01

Full Text Available Cerebral vein thrombosis (CVT is an infrequent condition with a large variety of causes that can lead to serious disabilities. However, in 20% to 35% of cases, no cause is found. In this study we evaluated the hereditary (P & C Proteins, antithrombin, mutation of prothrombin G20210A and factor V Leiden, other risk factors (hyperhomocycteinemia, factor VIII, ACL-ab, APL-ab, and OCP and clinical manifestations among a population of Iranian patients with CVT. 18 women and 10 men aged 16 to 50 years with CVT were screened for inherited and acquired coagulation risk factors. No one had an abnormal ACL-ab, APL-ab or antithrombin III deficiency. One had prothrombin G20210A mutation (heterozygot (3.6%. Hyperhomocycteinemia was observed in 5 patients (17.9%. APC-R was decreased in 3 (10.7%. 2 had positive factor V Leiden mutation (heterozygot (7.1%. 17 had an increased of factor VIII (60.7. PS and PC deficiencies were each detected in two cases (7.1%. Conclusion: Our study suggests that screening for inherited thrombophilia may be an integral part in the diagnostic workup and duration of treatment in patients with CVT.

VIII All-Russian symposium on molecular liquid chromatography and capillary electrophoresis. Program. Summary of reports

International Nuclear Information System (INIS)

2001-01-01

Program and summary of reports of the VIII All-Russian symposium on molecular liquid chromatography and capillary electrophoresis are performed. The meeting took place 15-19 October, 2001 in Moscow. Many problems of liquid and ion exchange chromatography, capillary electrophoresis, thin-layer chromatography have been discussed extensively. Reports covering properties of sorbents and devices for chromatography are incorporated in the collection [ru

MENINGKATKAN AKTIVITAS BELAJAR SISWA DENGAN MENGGUNAKAN METODE GROUP INVESTIGATION (GI PADA POKOK BAHASAN PASAR DI KELAS VIII SMP 5 KUDUS

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Mutthofiyah Mutthofiyah

2016-03-01

Full Text Available Penelitian ini bertujuan untukmeningkatkan aktivitas belajar siswa dengan menggunakan metode group investigation (GI pada pokok bahasan pasar pada penelitian ini menggunakan penelitian tindakan kelas (PTK. Dalam penelitian ini dirancang menggunakan siklus, masing-masing siklus dengan tahapan perencanaan, pelaksanaan tindakan, observasi dan refleksi. Teknik pengumpulan data pada penelitian ini adalah dokumentasi, observasi dan tes.Hasil penelitian menunjukkan melalui meningkatkan metode group investigation (GI aktivitas siswa SMP 5 Kudus ada peningkatan yang sigifikan, dari siklus I kelas VIII F 15,8 (41,62% meningkat di siklus II menjadi 24,8 (72,9%, sedangkan di kelas VIII G siklus I 18,5 (47,04% meningkat menjadi 26,2 (74,7%; melalui penerapan metode group investigation hasil belajar siswa SMP 5 kudus meningkat sangat signifkan, ketuntasan belajar secara klasikal dari kelas VIII F pra siklus sebesar 17,64% terjadi peningkatan 47% ke siklus I dan meningkat menjadi 82,35% di siklus II. Sedangkan di kelas VII G pra siklus sebesar 22,85% meningkat 54,28% di siklus I dan meningkat menjadi 94,28% di siklus II. Saran yang peneliti berikan adalah sebagai berikut:1Kepada para guru diharapkan dapat menerapkan pembelajaran kooperatif khususnya pembelajaran kooperatif tipe Group Investigation (GI dalam proses pembelajaran ekonomi dan mata pelajaran lainya dan mengembangkannya; 2 Kepada para peneliti selanjutnya diharapkan dapat melakukan penelitian tentang penerapan model pembelajaran yang dapat membangkitkan keaktifan siswa untuk belajar ekonomi. This study aims to improve students' learning activities using group investigation (GI on the subject of markets in class VIII SMP 5 Kudus. In this study is designed to use cycles, with each cycle stages of planning, action, observation and reflection. Data collection techniques in this study is documentation, observation and tests. Results showed through improved methods of group investigation (GI junior 5 high

Isidore of Seville and comici ueteres. Ad Isid., Orig. VIII 7.7

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Krzysztof Rzepkowski

2012-12-01

Full Text Available In chapter 7 of book VIII of Etymologies dedicated to Roman poets (De poetis, Isidore draws a dividing line between the so-called ueteres and noui comici. Among ueteres he counts Plautus, Accius, Terentius, although Accius, according to our knowledge, composed only tragedies and can hardly be considered a comic playwright. In this paper I try to prove that all the palaeographic, phonetic, historical, and literary arguments speak in favour of emending in the discussed passage the peculiar «Accius» to the expected «Caecilius» (i.e. Caecilius Statius.

Comparison of Clot-based, Chromogenic, and Fluorescence Assays for Measurement of Factor VIII Inhibitors in the U.S. Hemophilia Inhibitor Research Study

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Miller, Connie H.; Rice, Anne S.; Boylan, Brian; Shapiro, Amy D.; Lentz, Steven R.; Wicklund, Brian M.; Kelly, Fiona M.; Soucie, J. Michael

2015-01-01

Summary Background Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety, and assessment of population trends. Methods Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA), and a novel fluorescence immunoassay (FLI). Results NBA and CBA were performed on 1005 specimens and FLI on 272 specimens. CBA was negative on 880/883 specimens (99.7%) with Nijmegen-Bethesda units (NBU)NBA and negative CBA, 58.1% were FLI-negative, 12.9% had evidence of lupus anticoagulant, and 35.5% had non-time-dependent inhibition. CBA and FLI were positive on 72.4% and 100% of 1.0–1.9 NBU specimens and 43.1% and 50.0% of 0.5–0.9 NBU specimens. FLI detected antibodies in 98.0% of CBA-positive and 81.6% of NBA-positive specimens (P=0.004). Among 21 new inhibitors detected by NBA, 5 (23.8%) with 0.7–1.3 NBU did not react in CBA or FLI. Among previously positive patients with 0.5–1.9 NBU, 7/25 (28%) were not CBA or FLI positive. FLI was positive on 36/169 NBU-negative specimens (21.3%). Conclusions FVIII specificity could not be demonstrated by CBA or FLI for 26% of inhibitors of 0.5–1.9 NBU; such results must be interpreted with caution. Low titer inhibitors detected in clot-based assays should always be repeated, with consideration given to evaluating their reactivity with FVIII using more specific assays. PMID:23601690

Factors influencing radiation therapy student clinical placement satisfaction

Science.gov (United States)

Bridge, Pete; Carmichael, Mary-Ann

2014-01-01

Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning. PMID:26229635

Factors influencing radiation therapy student clinical placement satisfaction

Energy Technology Data Exchange (ETDEWEB)

Bridge, Pete; Carmichael, Mary-Ann [School of Clinical Sciences, Queensland University of Technology, Brisbane (Australia)

2014-02-15

Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning.

Factors influencing radiation therapy student clinical placement satisfaction

International Nuclear Information System (INIS)

Bridge, Pete; Carmichael, Mary-Ann

2014-01-01

Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

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Geoffrey K Isbister

Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

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

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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

Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

Energy Technology Data Exchange (ETDEWEB)

Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

2012-07-01

Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

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 et al., 1992). Here we report the cloning, purification, and 3D model of a novel family VIII esterase from Burkholderia multivorans UWC10. To our knowledge no report of esterolytic activity from B. multivorans is currently available. METHODOLOGY... stream_source_info Rashamuse1_2007_d.pdf.txt stream_content_type text/plain stream_size 9884 Content-Encoding UTF-8 stream_name Rashamuse1_2007_d.pdf.txt Content-Type text/plain; charset=UTF-8 Molecular Characterization...

Pisanello’s hat. The costume and weapons depicted in Pisanello’s medal for John VIII Palaeologus. A discussion of the saber and related weapons

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Alexander, David

2004-12-01

Full Text Available A group of six drawings by the Veronese artist Antonio Pisano depicted the Bizantine Emperor John VIII Paleologus wearing costumes and weapons according to islamic types. This paper studies these objects in relation to other contemporary islamic weapons.

Un grupo de seis dibujos del artista veronés Antonio Pisano representa al emperador bizantino Juan VIII Paleólogo vestido y armado según modelos islámicos. Este trabajo estudia dichos objetos en relación a otras armas islámicas contemporáneas.

Factors influencing visual rehabilitation after occlusion therapy in unilateral amblyopia in children.

Science.gov (United States)

Menon, Vimla; Chaudhuri, Zia; Saxena, Rohit; Gill, Kulwant; Sachdeva, M M

2005-12-01

Amblyopia is one of the most common causes of visual impairment in adults and children, and visual loss may be permanent if not treated in time. Though many studies have been done on occlusion therapy which is the mainstay in the treatment of unilateral amblyopia, discrepancies exist in literature about quantification of treatment and follow up measures. The present study was undertaken to evaluate the factors responsible for the successful outcome of treatment and the optimum time required for the same in children with unilateral amblyopia. Baseline characteristics of 63 verbal patients with unilateral amblyopia (strabismic, anisometropic, mixed) referred to the Strabismus and Amblyopia Clinic at the Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi between September 2001 to December 2002 who improved to the desired level of visual acuity after treatment for amblyopia in the mentioned time period, were analyzed to assess for factors that directly or indirectly influenced the optimum visual rehabilitation and the average duration of therapy required for the same. The evaluation included assessment of the baseline best-corrected visual acuity (BCVA) and refractive status in both eyes, the age at presentation, the type of amblyopia present, fixation pattern in the amblyopic eye, inter-eye visual acuity difference, and evaluation of compliance through a parental diary system. Baseline BCVA in the amblyopic eye was similar in all the three groups. Patients with anisometropic amblyopia showed a quicker response to therapy. Compliance to treatment was the major factor affecting the overall time required for a successful outcome in most cases. The overall time required for the treatment to be successful (including the period of maintenance) was about 1,089 h. This hospital-based study showed that the average duration of occlusion therapy to achieve stable isoacuity was 7.2 months with an average occlusion of 6-7 h/day. Compliance to therapy was the most

Penerapan Model Learning Cycle 5E untuk Meningkatkan Keterampilan Berpikir Kritis Siswa Pada Materi Fluida Statis Kelas VIII

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Irhamna Irhamna

2017-08-01

Full Text Available Penerapan model learning cycle 5E telah dilakukan pada siswa kelas VIII dengan materi fluida statis. Penelitian ini bertujuan untuk mendapatkan gambaran mengenai peningkatan keterampilan berpikir kritis siswa setelah diterapkan model learning cycle 5E pada materi fluida statis. Bentuk desain penelitian yang digunakan adalah pre-experimental dengan one group pre-test post-test design. Populasi pada penelitian ini adalah seluruh siswa kelas VIII di SMP Torsina Singkawang. Teknik pengambilan sampel menggunakan sampling purposive yang berjumlah 23 orang. Hasil penelitian menunjukkan bahwa model learning cyle 5E dapat meningkatkan keterampilan berpikir kritis siswa yaitu pada indikator pemecahan masalah dengan skor N-gain sebesar 0,43 dengan kategori sedang, indikator membuat keputusan dengan skor N-gain sebesar 0,42 dengan kategori sedang, indikator penyelidikan percobaan dengan skor N-gain sebesar 0,33 dengan kategori sedang dan indikator menyimpulkan dengan skor N-gain sebesar 0,37 dengan kategori sedang.

The influence of growth temperature and input V/III ratio on the initial nucleation and material properties of InN on GaN by MOCVD

International Nuclear Information System (INIS)

Wang, H; Jiang, D S; Zhu, J J; Zhao, D G; Liu, Z S; Wang, Y T; Zhang, S M; Yang, H

2009-01-01

The effects of growth temperature and V/III ratio on the InN initial nucleation of islands on the GaN (0 0 0 1) surface were investigated. It is found that InN nuclei density increases with decreasing growth temperature between 375 and 525 °C. At lower growth temperatures, InN thin films take the form of small and closely packed islands with diameters of less than 100 nm, whereas at elevated temperatures the InN islands can grow larger and well separated, approaching an equilibrium hexagonal shape due to enhanced surface diffusion of adatoms. At a given growth temperature of 500 °C, a controllable density and size of separated InN islands can be achieved by adjusting the V/III ratio. The larger islands lead to fewer defects when they are coalesced. Comparatively, the electrical properties of the films grown under higher V/III ratio are improved

Factors associated with developmental concern and intent to access therapy following discharge from the NICU.

Science.gov (United States)

Pineda, Roberta G; Castellano, Alison; Rogers, Cynthia; Neil, Jeffrey J; Inder, Terrie

2013-01-01

To determine factors associated with mothers' concern about infant development and intent to access therapy services following neonatal intensive care unit (NICU) discharge. Infant medical factors, magnetic resonance imaging results, neurobehavior at term, maternal factors, and maternal perceptions about developmental concern and intent to access therapy at NICU discharge were prospectively collected in 84 infants born premature (concern and intent to access therapy at NICU discharge. Decreased developmental concern was reported by mothers with more children (P = .007). Infant stress signs (P = .038), higher maternal education (P = .047), reading books (P = .030), and maternal depression (P = .018) were associated with increased developmental concern. More maternal education was associated with more intent to access services (P = .040). Maternal factors, rather than infant factors, had important associations with caregiver concern. In contrast, abnormal term neurobehavior and/or the presence of cerebral injury were not associated with caregiver concern about development.

Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation

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Wang H

2018-05-01

Full Text Available Han Wang,1–3 Yao Wang,1–3 Wentao Guo,4 Bin Du,1–3 Xiaobing Huang,1–3 Riping Wu,1–3 Baoyu Yang,1–3 Xiaoyan Lin,1–3,5 Yilan Wu6 1Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Stem Cell Research Institute, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, People’s Republic of China; 4School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Graduate School of Education, Fujian Medical University, Fuzhou, People’s Republic of China; 6School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Background: Mutated anaplastic lymphoma kinase (ALK drives the development of advanced non-small cell lung cancer (NSCLC. Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02, which demonstrated potent effects against the G1202R mutation. Methods: Molecular docking, conventional molecular dynamics (MD simulations, free energy calculations, and umbrella sampling (US simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R mutation. Results: JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib

Grotrian diagrams for highly ionized cobalt Co VIII through Co XXVII

Energy Technology Data Exchange (ETDEWEB)

Shirai, Toshizo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Sugar, J.; Wiese, W.L.

1997-07-01

Grotrian diagrams are presented to provide graphical overviews for 1,247 spectral lines of highly ionized cobalt, Co VIII through Co XXVII. In the usual diagram display such as that by Bashkin and Stoner (North-Holland, Amsterdam, 1975), the density of transitions is often too high to allow each transition to be drawn separately. Here in our modified diagrams, the transitions are also represented by lines connecting the upper and lower energy levels, but the lower energy levels are extended and repeated for successive configurations as needed. As a sequence, dense packing is avoided and all lines in a multiplet can be accommodated. (author)

A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors.

Science.gov (United States)

Streiff, Michael B; Ye, Xiaobu; Kickler, Thomas S; Desideri, Serena; Jani, Jayesh; Fisher, Joy; Grossman, Stuart A

2015-09-01

Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29-85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17-34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3-126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.

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.

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

Science.gov (United States)

Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

2017-08-15

Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

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Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

2015-06-19

Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for

Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial.

Science.gov (United States)

Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M; Rosendaal, Frits R

2015-12-16

To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Crossover trial. Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PENGARUH MODEL PEMBELAJARAN KOOPERATIF TIPE STAD BERBANTUAN PEMETAAN PIKIRAN (MIND MAPPING TERHADAP KEMAMPUAN MENULIS TEKS BERITA SISWA KELAS VIII SMP NEGERI 1 PANTI

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Ricci Gemarni Tatalia, M.Pd

2017-05-01

Full Text Available This study was generated from the problem of students’ ability in writing news texts ini class VIII, SMPN 1 Panti. Some of the problem were (1 lack of the students’ response towards news writing teaching and learning process, (2 lack of teacher’s creativity in designing interesting news sriting learning model, (3 no appropriate creative techniques applied by the teacher which could train the students to develop their skill in writing news texts and (4 lack of the students’ motivation in participating in teaching and learning process because of their lack of understanding in the elements of news. Thus, this study was aimed at escribing the effect of the students’ ability ini writing news texts in class VIII SMP N 1 Panti. This was a quantitative research with factorial 2x2 experimental design. The population was the students in class VIII SMPN 1 Panti. Sampling technique was done by using random sampling and the data was collected through test. The result of the study revealed that cooperative learning model with STAD mind mapping type affected the students’ ability in writing news texts

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

Science.gov (United States)

Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

2017-02-01

Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

Use of Folk Therapy in Taiwan: A Nationwide Cross-Sectional Survey of Prevalence and Associated Factors

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Shih, Chun-Chuan; Huang, Lu-Hsiang; Lane, Hsin-Long; Tsai, Chin-Chuan; Lin, Jaung-Geng; Chen, Ta-Liang; Yeh, Chun-Chieh; Liao, Chien-Chang

2015-01-01

Background. This study investigates the prevalence of and factors associated with users of folk therapy in Taiwan. Methods. Using data from the 2005 National Health Interview Survey and the National Health Insurance Research Database, we identified 16,750 adults aged 20 years and older. Sociodemographic factors, lifestyle, medical utilization, and health behaviors were compared between people using and not using folk therapy. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of factors associated with folk therapy were analyzed. Results. The one-month prevalence of folk therapy use was 6.8%, which was significantly associated with ages of 30–59 years (OR = 1.98, 95% CI = 1.49–2.63), women (OR = 1.63, 95% CI = 1.40–1.90), nonindigenous population (OR = 1.90, 95% CI = 1.14–3.17), having two or more unhealthy lifestyle habits (OR = 1.51, 95% CI = 1.26–1.81), high density of traditional Chinese medicine (TCM) physicians (OR = 1.40, 95% CI = 1.20–1.62), and being ill without receiving medical care in past six months (OR = 2.11, 95% CI = 1.76–2.53). Medical care utilization of TCM and Western medicine were also associated factors for folk therapy. Conclusions. The use of folk therapy is correlated with sociodemographics, lifestyle and health behaviors. PMID:26170878

Use of Folk Therapy in Taiwan: A Nationwide Cross-Sectional Survey of Prevalence and Associated Factors

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Chun-Chuan Shih

2015-01-01

Full Text Available Background. This study investigates the prevalence of and factors associated with users of folk therapy in Taiwan. Methods. Using data from the 2005 National Health Interview Survey and the National Health Insurance Research Database, we identified 16,750 adults aged 20 years and older. Sociodemographic factors, lifestyle, medical utilization, and health behaviors were compared between people using and not using folk therapy. Adjusted odds ratios (ORs and 95% confidence intervals (CIs of factors associated with folk therapy were analyzed. Results. The one-month prevalence of folk therapy use was 6.8%, which was significantly associated with ages of 30–59 years (OR = 1.98, 95% CI = 1.49–2.63, women (OR = 1.63, 95% CI = 1.40–1.90, nonindigenous population (OR = 1.90, 95% CI = 1.14–3.17, having two or more unhealthy lifestyle habits (OR = 1.51, 95% CI = 1.26–1.81, high density of traditional Chinese medicine (TCM physicians (OR = 1.40, 95% CI = 1.20–1.62, and being ill without receiving medical care in past six months (OR = 2.11, 95% CI = 1.76–2.53. Medical care utilization of TCM and Western medicine were also associated factors for folk therapy. Conclusions. The use of folk therapy is correlated with sociodemographics, lifestyle and health behaviors.

Evaluation of Consequences of Dust Positioned in Southwest of Iran on Coagulant Factors

Science.gov (United States)

Saeb, Keivan; Sarizade, Gholamreza; Khodadi, Mohammad; Biazar, Esmaeil

2013-01-01

Background: Various regions in Iran, especially the Khuzestan Province, have been covered by dust and dirt during the past two years due to environmental changes in the Middle East. We sought to evaluate the effect of these pollutants on the coagulant factors of people residing in Abadan and Khoramshahr, two major cities of Khuzestan Province. Methods: One hundred twenty-nine healthy individuals were enrolled into this study, and their prothrombin time as well as fibrinogen, platelet, and Factor VIII levels were measured before and after climate changes. Results: After climate changes, the mean prothrombin time decreased, while the fibrinogen, platelet, and Factor VIII levels rose. Conclusion: The results of this study suggest that the pollutants deployed in the Middle East can affect prothrombin time as well as fibrinogen, platelet, and Factor VII levels considerably and increase coagulant state. The pollutants can, consequently, increase the risk of cardiovascular diseases. It seems that cooperation at government levels between Iran and its neighboring countries is required to reverse desertification and avoid inaccurate usage of subterranean water resources so as to lessen air pollution. PMID:23825886

Estudo da articulação temporomandibular em camundongos deficientes de fator VIII

OpenAIRE

Patricia do Socorro Queiroz Feio

2010-01-01

Resumo: A hemofilia é uma doença hemorrágica hereditária ligada ao cromossomo X, decorrente da ausência ou da baixa quantidade no plasma dos fatores de coagulação Fator VIII (hemofilia A) ou do Fator IX (hemofilia B). Clinicamente, a hemofilia se caracteriza por episódios recorrentes de sangramentos profundos, que podem ocorrer espontaneamente ou em decorrência de traumatismos. O sistema músculo-esquelético é freqüentemente afetado pelos eventos hemorrágicos nos pacientes portadores de hemofi...

Risk factors for nutritional status determination and indications for preventive nutrition therapy in hospitalized gastroenterological patients

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Roganović Branka

2007-01-01

Full Text Available Background/Aim. Risk factors for the intrahospital nutritional status worsening (NSW have not been precisely defined in the literature. The objective was defining thoese factors among gastroenterological patients and defining the risk patients requiring a preventive nutritional therapy. Methods. In 650 gastroenterological patients, NSW was evaluated on the basis of reducing of the six parameters: body weight, body mass index (BMI, triceps skinfold thickness (TSF, midupper arm muscle circumference (MAMC, serum albumin level (ALB, and lymphocyte count (LYM. The influence on NSW was tested for 13 factors concerning characteristics of the patient, disease, and diagnostic procedures. Among the factors influencing significantly the NSW, primary and secondary risk factors were selected. After scoring of risk factors had been performed, the risk-score for NSW (RSNSW was defined. The critical value of RSNSW which required preventive nutritional therapy was also calculated. Results. The incidence of NSW was in the range 29.2%−57.9%. The presence of general complications and severe disease activity were considered as primary risk factors, whereas malignant disease, age above 71, hepato-billiary tract involvement, hospitalization longer than 14 days, and mobility worsening were considered as secondary risk factors. The best predictive value for the NSW was proved for the RSNSW ≥ 6. Because of that, preventive nutritional therapy should be indicated in patients presenting with both primary risk factors or in patients presenting with one primary factor combined with three secondary risk factors at least. Conclusion. There are 7 risk factors for NSW in gastroenterological patients, but they are not of the same importance - two primary and five secondary risk factors can be differentiated. Preventive nutritional therapy is indicated only in patients having both primary risk factors or in those presenting with one primary risk factor combined with three

EFFECT OF INFORMATION SERVICES USING THE MEDIA FILM TO SELF-CONFIDENCE STUDENT OF CLASS VIII SMP NEGERI 8 METRO

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MUDAIM MUDAIM

2015-06-01

Full Text Available Abstract: Pessimism and attitudes that consider themselves weak and does not have the ability when facing a problem will make individual impediment in the task of development. Problems confidence that underlies the research are: a Students are less confident in the ability it has, b Students feel pessimistic when faced with an issue, c Student perception subjectively, d Students still do not do the work independently, and e negative minded students with a state-owned. The problems of this study are whether there is an influence of information services using the medium of film to the confidence of eighth-grade students of SMP Negeri 8 Metro. The purpose of this study was to determine whether there is an influence of information services using the medium of film to the self-confidence of students in class VIII SMP Negeri 8 Metro. Subject participant is graders VIII-E total 30 students. Data were collected by questionnaire self-confidence and analyzed the data used is the t-test. The results of this study, shown by the difference in change scores of confidence from the pre-test and post-test of 17.1. Testing the hypothesis obtained calculation results thitung6,036> table = 1.699. The conclusion is that the information services implemented using the film medium can be a positive influence on self-esteem, especially students of class VIII. The advice given is to use the medium of film should be done intensively and more creative by BK teachers in giving information service. Keywords: Confidence, Service Information Using Media Film.

75 FR 36426 - Legislative Changes to Nursing Student Loan Program Authorized Under Title VIII of the Public...

Science.gov (United States)

2010-06-25

... Changes to Nursing Student Loan Program Authorized Under Title VIII of the Public Health Service Act....) 111-148. Section 5202 of the ACA changes the Nursing Student Loan (NSL) program by: (1) Increasing the... degree in nursing. Below are details on how the ACA changes Sections 836(a), 836(b)(1), and 836(b)(3) of...

Modifications to LLNL Plutonium Packaging Systems (PuPS) to achieve ASME VIII UW-13.2(d) Requirements for the DOE Standard 3013-00 Outer Can Weld

International Nuclear Information System (INIS)

Riley, D; Dodson, K

2001-01-01

The Lawrence Livermore National Laboratory (LLNL) Plutonium Packaging System (PuPS) prepares packages to meet the DOE Standard 3013 (Reference 1). The PuPS equipment was supplied by the British Nuclear Fuels Limited (BNFL). The DOE Standard 3013 requires that the welding of the Outer Can meets ASME Section VIII Division 1 (Reference 2). ASME Section VIII references to ASME Section IX (Reference 3) for most of the welding requirements, but UW-13.2 (d) of Section VIII requires a certain depth and width of the weld. In this document the UW-13.2(d) requirement is described as the (a+b)/2t s ratio. This ratio has to be greater than or equal to one to meet the requirements of UW-13.2(d). The Outer Can welds had not been meeting this requirement. Three methods are being followed to resolve this issue: (1) Modify the welding parameters to achieve the requirement, (2) Submit a weld case to ASME that changes the UW-13.2(d) requirement for their review and approval, and (3) Change the requirements in the DOE-STD-3013. Each of these methods are being pursued. This report addresses how the first method was addressed for the LLNL PuPS. The experimental work involved adjusting the Outer Can rotational speed and the power applied to the can. These adjustments resulted in being able to achieve the ASME VIII, UW-13.2(d) requirement

Patients' views toward knee osteoarthritis exercise therapy and factors influencing adherence - a survey in China.

Science.gov (United States)

Zhou, Zhiwei; Hou, Yunfei; Lin, Jianhao; Wang, Kai; Liu, Qiang

2018-05-01

To understand the views toward exercise therapy for knee osteoarthritis (KOA) in China and to analyze factors affecting treatment adherence. A survey-based study, which included multiple choice and open-ended questions on knee OA exercise therapy was conducted in a Chinese population. The content included the respondents' attitudes and beliefs, willingness to receive treatment, and reasons why they could or could not adhere to the treatment. We used Chi-squared tests to compare cognitive differences between the patients and non-patient groups. A total of 1,069 people responded to the questionnaire, and the response rate was 81.8%. A total of 93.6% of the patients thought that they could adhere to the exercise treatment if they received professional advice and prescriptions. The following questionnaire items achieved consensus: 'Increasing the strength of the muscles around the knee stops the knee pain from getting worse,' 'It is the person's own responsibility to continue doing their exercise program,' 'How helpful the exercise program will be determines how well a person sticks to it,' 'Health professionals should educate patients with knee pain about how to change their lifestyle for the better,' and 'Exercise for knee pain is most helpful when it is designed for each person, to suit their own particular needs.' Patient adherence was affected by multiple factors, and some negative factors included 'forgetfulness,' 'getting joint symptoms improved after therapy,' 'professional guidance, subsequent monitoring and supervision,' 'willing to enhance overall health and quality of life,' 'having no time,' 'occupational factors,' 'considering that the pain would worsen while/after exercise,' and 'family factors.' A general Chinese population accepted exercise therapy for treating KOA in our survey. Education is necessary because patients were uncertain and had misunderstandings regarding the potential benefits of exercise therapy. Some factors related to treatment

PENINGKATAN AKTIVITAS DAN HASIL BELAJAR POKOK BAHASAN PASAR DENGAN METODE RESITASI PADA SISWA KELAS VIII SMP NEGERI 24 SEMARANG TAHUN AJARAN 2013/2014

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Diinul Qoyyimah

2013-11-01

Full Text Available Aktivitas siswa kelas VIII pada mata pelajaran ekonomi SMP Negeri 24 Semarang pada pokok bahasan pasar masih rendah sehingga berdampak pada hasil belajar siswa yang masih dibawah KKM. Salah satu penyebabnya karena guru masih menerapkan metode belajar yang sama dalam waktu yang lama sehingga mengakibatkan rendahnya perolehan hasil belajar. Melalui penerapan metode ceramah bervariasi dan resitasi diharapkan siswa dapat belajar dengan santai dan senang dalam mengikuti proses pembelajaran. Penelitian ini bertujuan untuk mengetahui penerapan metode resitasi, dapat meningkatkan aktivitas dan hasil belajar siswa. Metode penelitian menggunakan penelitian tindakan kelas. Prosedur penelitian dilakukan dimulai dengan perencanaan, pelaksanaan, observasi dan refleksi. Metode pengumpulan data dengan dokumentasi dan tes. Hasil penelitian menyatakan bahwa ada peningkatan aktivitas siswa dan hasil belajar siswa materi pasar pada kelas VIII SMP Negeri 24 Semarang tahun 2013/2014. The students’ activity in VIII class of economic subject in SMP Negeri 24 Semarang in the subject matter of market topic is still low so it has the impact on the students’ learning outcome which is still under KKM requirements. One of the causes is because the teachers are still apply the same learning method in a long time so it resulted in low learning outcomes acquisition.through the application of various conventional methods and recitation are expected that students can learn easily and pleasure in participating of learning process. This study aims to determine the application of recitation method which can improve the activity and students’ learning outcomes. The research method using classroom action research. The research procedure begins with planning, implementation, observation and reflection. Methods of data collection carried out by documentation and test. The result of research states that there is an increasing activity and students’ learning outcomes in the

Design local exhaust ventilation on sieve machine at PT.Perkebunan Nusantara VIII Ciater using design for assembly (DFA) approach with Boothroyd and Dewhurst method

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Khalqihi, K. I.; Rahayu, M.; Rendra, M.

2017-12-01

PT Perkebunan Nusantara VIII Ciater is a company produced black tea orthodox more or less 4 tons every day. At the production section, PT Perkebunan Nusantara VIII will use local exhaust ventilation specially at sortation area on sieve machine. To maintain the quality of the black tea orthodox, all machine must be scheduled for maintenance every once a month and takes time 2 hours in workhours, with additional local exhaust ventilation, it will increase time for maintenance process, if maintenance takes time more than 2 hours it will caused production process delayed. To support maintenance process in PT Perkebunan Nusantara VIII Ciater, designing local exhaust ventilation using design for assembly approach with Boothroyd and Dewhurst method, design for assembly approach is choosen to simplify maintenance process which required assembly process. There are 2 LEV designs for this research. Design 1 with 94 components, assembly time 647.88 seconds and assembly efficiency level 23.62%. Design 2 with 82 components, assembly time 567.84 seconds and assembly efficiency level 24.83%. Design 2 is choosen for this research based on DFA goals, minimum total part that use, optimization assembly time, and assembly efficiency level.

Exposure to occupational therapy as a factor influencing recruitment to the profession.

Science.gov (United States)

Byrne, Nicole

2015-08-01

This article provides insight into the impact that exposure to an occupational therapist, in personal capacity or via a professional interaction, has on the decision to enter an occupational therapy undergraduate programme. A quantitative survey was completed by 139 occupational therapy students. The survey tool focussed on the students' exposure to a range of allied health professions (e.g. occupational therapy, physiotherapy, psychology) and investigated how exposure to occupational therapy had influenced their decision to enter the programme. The results indicated that over 70% of respondents had personal professional exposure to occupational therapy prior to making a career decision. Exposure most frequently involved occupational therapy intervention of a friend or family member. The majority of students who had professional exposure to occupational therapy (e.g. family, self, friend received occupational therapy) identified that it was the most influential factor in their career choice. Forty per cent of the occupational therapy students did not enter the programme straight from school and the influence of 'working with an occupational therapist' was noteworthy for mature aged students. Occupational therapists need to consider that every interaction they have with the community provides valuable information regarding the profession and gives insight into occupational therapy as a potential career path for other people. Additionally, the current research identifies there were differences in the impact, type and number of exposures for different student groups, and this potentially offers some insight into ways in which occupational therapy could target specific groups within the community to increase future diversity in the profession. © 2015 Occupational Therapy Australia.

Patient adherence to antihypertensive therapy and its individual psychological factors

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Lidia Trachuk

2016-09-01

Full Text Available Background. In the treatment of chronic, especially asymptomatic pathology one of the main problem is the adherence to therapy. Patients with arterial hypertension need long-term, often lifelong medication, and how strictly they adhere to prescriptions often determines the course of the disease and the medical measures effectiveness. According to statistics, more than half of patients with hypertension are characterized by low compliance, which leads to complications of this disease. The objective of the research is to identify and analize the individual psychological factors that determine patient adherence to antihypertensive therapy. Methods and materials. This study was conducted during 2011-2013 at the cardiology departments of the Kyiv Alexander Hospital, polyclinics number 2 Shevchenko district in Kyiv, Desnyanskiy clinic №3 district in Kyiv, medical center "Adonis plus". We examined 203 patients with arterial hypertension (average age 53,5 ± 4,5 years. Methods: socio-demographic, clinical, clinical and psychological, psychodiagnostical, mathematical and statistical methods. Psychodiagnostical method included: 8-item Morisky medical adherence scale (Morisky D. E., 2008; self-assessment anxiety scale Charles D. Spielberger – Y.L Hanin (A.V. Batarshev, 2005; the Minnesota Multiphasic Personality Inventory questionnaire (MMRI (F.B. Berezin, 1994; "The level of subjective control" (A.A. Rean, 2001; "Index of attitudes to health" (S.D. Deryabo, VA Yasvin, 2000. Results. According to the results of 8-item Morisky medical adherence scale patients were divided into 3 groups according to the level of compliance - with high (26.11%, average (24.14% and low (49.75% levels of adherence to antihypertensive therapy. The individual-psychological predictors of poor adherence to antihypertensive therapy include the following personal characteristics of patients: a low level of intensity of attitude to health, internal type of subjective control, a

Factors affecting the stability of visual function following cessation of occlusion therapy for amblyopia.

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Tacagni, Daniel J; Stewart, Catherine E; Moseley, Merrick J; Fielder, Alistair R

2007-06-01

To identify factors that predict which children with amblyopia are at greatest risk of regression of visual acuity (VA) following the cessation of occlusion therapy. A retrospective analysis was performed of 182 children (mean age at cessation of treatment; 5.9+/-1.6 years) who had undergone occlusion therapy for unilateral amblyopia, and had been followed up at least once within 15 months of cessation. Statistical analysis was used to identify whether change in VA following treatment cessation had any association with various factors, including the child's age, type of amblyopia, degree of anisometropia, initial severity of amblyopia, binocular vision status, length and dose of occlusion therapy, and VA response to treatment. At 1 year, follow-up from treatment cessation, children with "mixed" amblyopia (both anisometropia and strabismus) demonstrated significantly (p=0.03) greater deterioration in VA (0.11+/-0.11 log units) than children with only anisometropia (0.02+/-0.08 log units) or only strabismus (0.05+/-0.10 log units). However, none of the other factors investigated were found to be significant predictors. This study supports previous research that it is possible to identify those children most at risk of deterioration in VA following cessation of occlusion therapy. The presence of mixed amblyopia was the only risk factor identified in this study. Management of amblyopia should take this into account, with a more intensive follow-up recommended for those with both anisometropia and strabismus (mixed) amblyopia.

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis.

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Valentino, L A; Pipe, S W; Collins, P W; Blanchette, V S; Berntorp, E; Fischer, K; Ewenstein, B M; Oh, M; Spotts, G

2016-07-01

We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL(-1) , with higher values associated with a decreased risk for all bleeding (joint and non-joint; P 20 IU dL(-1) was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL(-1) provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Risk factors for persistent atrial fibrillation following successful hyperthyroidism treatment with radioiodine therapy.

Science.gov (United States)

Zhou, Zhen-Hu; Ma, Long-Le; Wang, Le-Xin

2011-01-01

To investigate the predicting factors for persistent atrial fibrillation (AF) following radioiodine therapy for hyperthyroidism. Standard 12-lead ECG and 24-h Holter monitoring were performed in 94 patients (38 males, mean age 46.1±8.2 years) with persistent AF following radioiodine therapy for hyperthyroidism. Left ventricular (LV) function was assessed with two-dimensional echocardiography. Euthyroidism or hypothyroidism was achieved in 81% and 19% of the patients, respectively, after radioiodine therapy. At the end of follow-up (1.6±1.3 years), LV ejection fraction in the 52 patients with LV dysfunction was increased from 39.3±3.3% to 59.0±5.5% (ptreatment paroxysmal AF, no AF was documented during the follow-up. In the 45 patients with pre-treatment persistent AF, AF was found in 27 (60%) during the follow-up. Multivariate logistic regression analysis showed that more than 55 years old in age (RR 2.76, 95% CI: 1.16-8.79, phyperthyroidism (RR 3.08, 95% CI: 1.22-11.41, ptreatment atrial fibrillation (RR 2.96, 95% CI: 1.31-7.68, phyperthyroidism and pre-treatment duration of AF are risk factors for persistent AF following radioiodine therapy.

Pitfalls in hemostasis exploration, a case report of a girl with Henoch-Schönlein type vasculitis

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Arghirescu Smaranda

2017-07-01

Full Text Available The adequate performance and correct interpretation of assays for coagulation factor inhibitors play a critical role for the hemostasis laboratory. Both, false positive and false negative inhibitor assays may be reported, leading to erroneous patient’s management. Therefore, we decided to present a case with a spurious image of an exceptionally rare acquired combined haemophilia A, B and C, with severe factor ( F VIII, IX and XI deficiency, associated with high titre anti - F VIII, IX and XI inhibitors in a 4 years old girl with Henoch-Schönlein type vasculitis. Finally, performing, beside coagulometric methods also antigenic ELISA assays, we had to invalidate the diagnosis. The performance of antiphospholipd antibodies clarified the diagnosis , finally concluding as definite diagnosis Transient Lupus Anticoagulant Syndrome, with decisive impact on therapy and follow-up.

Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

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Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

2016-01-01

IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

Innovative physical therapy practice: a qualitative verification of factors that support diffusion of innovation in outpatient physical therapy practice.

Science.gov (United States)

Sabus, Carla; Spake, Ellen

2016-01-01

New ideas, methods, and technologies spread through cultures through typical patterns described by diffusion of innovation (DOI) theory. Professional cultures, including the physical therapy profession, have distinctive features and traditions that determine the adoption of practice innovation. The Consolidated Framework for Implementation Research (CFIR) proposes a framework of innovation implementation specific to health care services. While the CFIR has been applied to medical and nursing practice, it has not been extended to rehabilitation professions. The purpose of this qualitative study was to verify the CFIR factors in outpatient physical therapy practice. Through a nomination process of area rehabilitation managers and area directors of clinical education, 2 exemplar, outpatient, privately owned physical therapy clinics were identified as innovation practices. A total of 18 physical therapists (PTs), including 3 owners and a manager, participated in the study. The 2 clinics served as case studies within a qualitative approach of directed content analysis. Data were collected through observation, spontaneous, unstructured questioning, workflow analysis, structured focus group sessions, and artifact analysis including clinical documents. Focus group data were transcribed. All the data were analyzed and coded among 4 investigators. Through data analysis and alignment with literature in DOI theory in health care practice, the factors that determine innovation adoption were verified. The phenomena of implementation in PT practice are largely consistent with models of implementation in health care service. Within the outpatient practices studied, patient-centered care and collaborative learning were foundational elements to diffusion of an innovation. Innovation in outpatient physical therapy practice can be understood as a social process situated within the culture of the physical therapy professional that follows predictable patterns that strongly align with

METHODOLOGY OF THE DRUGS MARKET VOLUME MODELING ON THE EXAMPLE OF HEMOPHILIA A

OpenAIRE

N. B. Molchanova

2015-01-01

Hemophilia A is a serious genetic disease, which may lead to disability of a patient even in early ages without a required therapy. The only one therapeutic approach is a replacement therapy with drugs of bloodcoagulation factor VIII (FVIII). The modeling of coagulation drugs market volume will allow evaluation of the level of patients’ provision with a necessary therapy. Modeling of a “perfect” market of drugs and its comparison with the real one was the purpose of the study. During the mode...

Delaying ACL reconstruction and treating with exercise therapy alone may alter prognostic factors for 5-year outcome

DEFF Research Database (Denmark)

Filbay, Stephanie R; Roos, Ewa M; Frobell, Richard B

2017-01-01

, body mass index, preinjury activity level, education and smoking. RESULTS: For all participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse baseline 36-item Short-Form Mental Component Scores were associated with worse outcomes. Treatment with exercise therapy alone......AIM: Identify injury-related, patient-reported and treatment-related prognostic factors for 5-year outcomes in acutely ACL-ruptured individuals managed with early reconstruction plus exercise therapy, exercise therapy plus delayed reconstruction or exercise therapy alone. METHODS: Exploratory...... was a prognostic factor for less knee symptoms compared with early reconstruction plus exercise therapy (regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was associated with worse sport/recreation function (-14.4, 95% CI -27.6 to -1.3) and osteochondral lesions were associated with worse...

Radiation therapy for Kasabach-Merritt syndrome. Analysis of unfavorable factors in 5 children

International Nuclear Information System (INIS)

Kawamori, Jiro; Saito, Tsutomu; Tanaka, Yoshiaki; Sato, Katsuhiko.

1996-01-01

During the past 10 years, five infants with Kasabach-Merritt syndrome (K-M) receiving radiation therapy were reported. We investigated whether radiation therapy for K-M was useful and what the unfavorable factors of K-M were. During the past 10 years, we have treated five infants with K-M. The syndrome occurred at ages ranging from birth to 4 months. The incidence of female to male ratio was 3:2. Among 5 cases, the site of hemangioma was as follows; shoulder, anterior chest wall, lower abdominal wall, face and neck and inguinal site. All 5 cases received medication to control the coagulopathy including prednisone and blood transfusion at first. Because the platelet count and the bleeding tendency did not improve in any case, these cases received radiation therapy. Total dose ranged from 5 to 10 Gy and fraction-size ranged from 0.5 to 1.75 Gy. Irradiation session was 2 or 3 times per week. In 5 cases, 4 cases showed cure of bleeding tendency and disappearance of tumor, and survived. In these 4 cases, normalization of platelet count was obtained at the early phase of dose ranging from 3 to 5 Gy by radiation therapy. In the remaining case, bleeding tendency was improved at the late phase by initial radiation therapy, however, after that immediately relapsed. In this case, the salvage radiation therapy was not effective and she died from airway obstruction. This case was of neonatal age and had bulky neck tumor. We recognized that radiation therapy was effective for K-M. A serious case was of neonatal age and had bulky neck tumor. It was estimated that the unfavorable factors of K-M were neonatal case and bulky neck tumor case. (author)

Pathogen inactivation in fresh frozen plasma using riboflavin and ultraviolet light: Effects on plasma proteins and coagulation factor VIII

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Stanojković Zoran

2011-01-01

Full Text Available Background/Aim. Riboflavin (vitamin B2 activated by ultraviolet (UV light, produces active oxygen which damages cell membrane and prevents replication of the carrier of diseases (viruses, bacteria, protozoa in all blood products. The aim of this study was to establish the influence of the process of photo inactivation in pathogens using riboflavin and UV rays on the concentration of coagulation factor VIII:C (FVIII:C and proteins in plasma that were treated before freezing. Methods. The examination included 20 units of plasma, separated from whole blood donated by voluntary blood donors around 6 hours from the moment of collection. The units were pooled and separated in to two groups: one consisted of 10 control units and the other of 10 experimental units. Experimental units of the plasma were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 minutes. Furthermore, 35 mL of saline solution was added to the control plasma. One sample for examining was taken from the control plasma (KG and two residual were taken from experimental plasma after the addition of riboflavin either before (EG1 or post illumination (EG2. Results. Comparing the mean values of FVIII:C (% we noticed statistically significantly higher level in the EG1 group than in the EG2 group (65.00 ± 4.52 vs 63.20 ± 4.73; t = 4.323, p = 0.002, while between the KG and experimental groups (EG1 and EG2 there was no statistically significant difference in the concentration of FVIII:C. There was a statistically significant decrease of albumin concentration (g/L in the EG2 group comparing to the KG (33.35 ± 0.94 vs 31.94 ± 0.84; t = 3.534, p = 0.002, but there was no mentioned difference in albumin concentration between the KG and the EG1, so as between the EG1 and the EG2. Conclusion. Plasma inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA keeps all the

Development, upscaling and validation of the purification process for human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII produced in a human cell-line.

Science.gov (United States)

Winge, Stefan; Yderland, Louise; Kannicht, Christoph; Hermans, Pim; Adema, Simon; Schmidt, Torben; Gilljam, Gustav; Linhult, Martin; Tiemeyer, Maya; Belyanskaya, Larisa; Walter, Olaf

2015-11-01

Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Innovative physical therapy practice: a qualitative verification of factors that support diffusion of innovation in outpatient physical therapy practice

Directory of Open Access Journals (Sweden)

Sabus C

2016-12-01

Full Text Available Carla Sabus,1 Ellen Spake2 1Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, 2Rockhurst University, Kansas City, MO, USA Background and purpose: New ideas, methods, and technologies spread through cultures through typical patterns described by diffusion of innovation (DOI theory. Professional cultures, including the physical therapy profession, have distinctive features and traditions that determine the adoption of practice innovation. The Consolidated Framework for Implementation Research (CFIR proposes a framework of innovation implementation specific to health care services. While the CFIR has been applied to medical and nursing practice, it has not been extended to rehabilitation professions. The purpose of this qualitative study was to verify the CFIR factors in outpatient physical therapy practice.Design: Through a nomination process of area rehabilitation managers and area directors of clinical education, 2 exemplar, outpatient, privately owned physical therapy clinics were identified as innovation practices. A total of 18 physical therapists (PTs, including 3 owners and a manager, participated in the study.Methods: The 2 clinics served as case studies within a qualitative approach of directed content analysis. Data were collected through observation, spontaneous, unstructured questioning, ­workflow analysis, structured focus group sessions, and artifact analysis including clinical documents. Focus group data were transcribed. All the data were analyzed and coded among 4 investigators.Results: Through data analysis and alignment with literature in DOI theory in health care practice, the factors that determine innovation adoption were verified. The phenomena of implementation in PT practice are largely consistent with models of implementation in health care service. Within the outpatient practices studied, patient-centered care and collaborative learning were foundational

Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

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Sara Taveras Alam

2014-01-01

Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

The Factor Structure of The Working Alliance Inventory in Cognitive-Behavioral Therapy

Science.gov (United States)

Andrusyna, Tomasz P.; Tang, Tony Z.; DeRubeis, Robert J.; Luborsky, Lester

2001-01-01

Studies of the therapeutic alliance in cognitive-behavioral therapy (CBT) have varied in their results, necessitating a deeper understanding of this construct. Through an exploratory factor analysis of the alliance in CBT, as measured by the Working Alliance Inventory (shortened, observer-rated version), the authors found a two-factor structure of alliance that challenges the commonly accepted one general factor of alliance. The results suggest that the relationship between therapist and client (Relationship) may be largely independent of the client's agreement with and confidence in the therapist and CBT (Agreement/ Confidence), necessitating independent measures of these two factors, not one measure of a general alliance factor. PMID:11402080

Multi-factor analysis on events related to hematological toxicity in 153Sm-EDTMP palliative therapy for skeletal metastases

International Nuclear Information System (INIS)

Zhan Hongwei; Yu Xiaoling; Ye Xiaojuan; Bao Chengkan; Sun Da; He Gangqiang

2006-01-01

Objective: To investigate the clinical factors related to hematological toxicity induced by intravenous samarium-153 ethylenediaminetetramethylene phosphonic acid ( 153 Sm-EDTMP) treatment. Methods A total of 206 patients with bony metastases treated with 153 Sm-EDTMP were retrospectively analyzed. Logistic regression (SPSS 10.0 for Windows) and correlation analysis were used to evaluate the factors concerned. Results: Age of the patient, number of bone metastatic lesion, chemotherapy before 153 Sm-EDTMP therapy, concurrent radiotherapy and repeat-times of 153 Sm-EDTMP treatments were found the individual factors related to hematological toxicity. Chemotherapy before 153 Sm-EDTMP, concurrent radiotherapy, medication for normal blood counting and repeat-times of 153 Sm-EDTMP treatments were the hematological toxicity factors in multi-factor analysis. Conclusion: In 153 Sm-EDTMP therapy, several factors were found related to hematological toxicity suggesting more attention be paid to the change of blood cell counting after the palliative therapy. (authors)

Energies and lifetimes of excited states in copperlike Kr VIII

International Nuclear Information System (INIS)

Livingston, A.E.; Curtis, L.J.; Schectman, R.M.; Berry, H.G.

1980-01-01

The spectrum of Kr VIII has been observed between 180 and 2000 A by using foil excitation of 2.5--3.5-MeV krypton ions. Twenty new transitions have been classified and eleven new excited-state energies have been determined within the n=4 --7 shells. The ionization potential is derived to be 1 015 800 +- 200 cm -1 . The excited-state energies and fine structures are compared with recent relativistic Hartree-Fock calculations. The 4p-state lifetime has been measured by performing a simultaneous analysis of decay data for the 4p level and for its dominant cascade-repopulating levels. The 4p lifetime is found to be 30% shorter than previously measured values and is in excellent agreement with the result of a recent multiconfiguration Hartree-Fock calculation. The source of the discrepancy between this result and earlier measurements is discussed

The Utilization of Rehabilitation in Patients with Hemophilia A in Taiwan: A Nationwide Population-Based Study.

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Chien-Min Chen

Full Text Available Rehabilitation plays an important role in the physical health of patients with hemophilia. However, comprehensive information regarding the utilization of rehabilitation for such patients remains scarce.This population-based study aimed to examine the characteristics, trends, and most important factors affecting rehabilitation usage in patients with hemophilia A using a nationwide database in Taiwan.Data from 777 patients with hemophilia A who were registered in the National Health Insurance Research Database between 1998 and 2008 were analyzed using SAS 9.0.Musculoskeletal or nervous system-related surgical procedures and clotting factor VIII concentrate costs were identified as factors affecting rehabilitation usage; musculoskeletal or nervous system-related surgical procedures (odds ratio = 3.788; P < 0.001 were the most important predictor of whether a patient with hemophilia A would use rehabilitation services. Joint disorders, arthropathies, bone and cartilage disorders, intracranial hemorrhage, and brain trauma were common diagnoses during rehabilitation use. The costs of physical therapy (physiotherapy comprised the majority (71.2% of rehabilitation therapy categories. Increasingly, rehabilitation therapy was performed at physician clinics. The total rehabilitation costs were <0.1% of the total annual medical costs.Musculoskeletal or nervous system-related surgical procedures and increased use of clotting factor VIII concentrate affect the rehabilitation utilization of patients with hemophilia A the most. The findings in this study could help clinicians comprehensively understand the rehabilitation utilization of patients with hemophilia A.

Factors predicting successful discontinuation of continuous renal replacement therapy.

Science.gov (United States)

Katayama, S; Uchino, S; Uji, M; Ohnuma, T; Namba, Y; Kawarazaki, H; Toki, N; Takeda, K; Yasuda, H; Izawa, J; Tokuhira, N; Nagata, I

2016-07-01

This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

Science.gov (United States)

Sadashiv, Mucheli Shravan; Rupali, Priscilla; Manesh, Abi; Kannangai, Rajesh; Abraham, Ooriapadickal Cherian; Pulimood, Susanne A; Karthik, Rajiv; Rajkumar, S; Thomas, Kurien

2017-12-01

Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Univariate analysis showed significant association with 1) Self-reported nonadherenceART and thus help development of targeted interventions.

Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.

Science.gov (United States)

Tuszynski, Mark H; Yang, Jennifer H; Barba, David; U, Hoi-Sang; Bakay, Roy A E; Pay, Mary M; Masliah, Eliezer; Conner, James M; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H

2015-10-01

Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment. To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined. Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay. Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic

Report on corrections and future considerations for Appendices II–VIII of the International Code of Nomenclature for Algae, Fungi, and Plants

Science.gov (United States)

For the first time, the main text and Appendices II–VIII of the International Code of Nomenclature were separately published following decisions of the Melbourne Nomenclature Section, which contributed to subsequent development of an online resource capable of producing the Appendices in real time. ...

Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

DEFF Research Database (Denmark)

Nossent, Anne Yaël; Robben, J H; Deen, P M T

2010-01-01

SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

X-ray spectral line coincidences between fluorine VIII (and IX) and transition metal lines

International Nuclear Information System (INIS)

Charatis, G.; Rockett, P.D.; Burkhalter, P.G.

1983-01-01

X-ray spectroscopy was performed in the 12 to 15 A region, recording L-shell lines from selected laser-irradiated transition metals. Line coincidences and near coincidences were identified between Fe, Cr, Mn, and Ni L-spectra, and F VIII and F IX K-shell lines. Wavelengths were determined to accuracies of 1 to 3 mA and will be utilized in selecting potential pumping candidates in future x-ray lasing schemes. High-resolution x-ray spectra were collected under controlled illumination and target conditions using 1.05 μm and 0.527 μm laser excitation with the KMS CHROMA laser

PENERAPAN MODEL PEMBELAJARAN BAKULIKAN UNTUK MENINGKATKAN KEMAMPUAN BERSIKAP ILMIAH PADA KONSEP PEMANTULAN CAHAYA KELAS VIII

Directory of Open Access Journals (Sweden)

N. A. Shofiah

2012-01-01

Full Text Available Penelitian tindakan kelas yang bertujuan untuk meningkatkan kemampuan bersikap ilmiah, telah dilakukan di kelas VIII semester IIpada sub pokok bahasan pemantulan cahaya. Untuk meningkatkan kemampuan bersikap ilmiah diterapkan model pembelajaranbakulikan. Penelitian tindakan kelas ini terdiri dari tiga sikus, dengan masing-masing siklus terdiri dari empat tahapan yaituperencanaan, pelaksanaan, observasi dan refleksi. Data sikap ilmiah siswa diambil dari lembar angket dan lembar observasi. Datahasil belajar kognitif diambil dari evaluasi yang ada di LKS tiap akhir siklus dan data hasil belajar psikomotorik diambil dari lembarobservasi tiap akhir siklus. Hasil penelitian menyatakan bahwa sikap ilmiah siswa mengalami peningkatan walaupun tidaksignifikan. Hasil belajar kognitif dan keterampilan psikomotorik siswa mengalami peningkatan tiap siklus dan mencapai ketuntasanpada siklus III. A classroom action research aimed to improve scientific attitude skill had been done in second semester of grade VIII MTs on thesubtopic light reflection. The 'bakulikan' learning model was chosen for improving the scientific attitude skills of the students. Thisaction research consisted of three cycles, and each cycle has four stages, namely, planning, conducting, observation andreflection. The data obtained through questionnaire and observation sheets. The cognitive achievement drawn from the evaluationon each worksheet at the end of each cycle, and the psychometrics recorded from observation sheet. The study concludes that thescientific attitude skill improved significantly. The achievement on cognitive and psychometrics increase gradually on each cycleand get mastery at the end of the last cycle.Keywords: bakulikan; classroom action research; scientific attitude

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

Science.gov (United States)

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

EK(b)P Keskkomitee VIII pleenumi stenogramm / tõlk. Mart Arold, tõlk. Jaan Isotamm

Index Scriptorium Estoniae

1999-01-01

EK(b)P Keskkomitee VIII pleenum, 21.-23. märts 1950. Sõnavõtud: N. Karotamm, P. Ponomarenko, I. Käbin, V. Kuusik, A. Jaanus, V. Hiznjakov, E. Ristimägi, I. Suija, H. Ajo, A. Meri, G. Abels, M. Assin, G. Latõshov, Rumjantsev, Müürisepp. Kommenteerinud Viktor Niitsoo. Algus: Akadeemia (1998) nr. 12, lk. 2655-2683 ; Järg nr.2;3;4;5;6;7;8;9;10 lk.415-446;639-670;863-894;1087-1118;1310-1342;1534-1566;1759-1790;2017-2048;2220-2256

Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway.

LENUS (Irish Health Repository)

Korpanty, Grzegorz

2010-01-01

Lung cancer (LC) is a leading cause of death worldwide. Recent advances in chemotherapeutic agents have not yielded any significant improvement in the prognosis of patients with LC. The five-year survival rate for all combined disease stages remains about 15%. For this reason, new therapies such as those that inhibit tumor angiogenesis or block activity of growth factor receptors are of special interest in this group of patients. In this review we will summarize the most recent clinical data on biologic therapies that inhibit tumor angiogenesis in LC, focusing on those that are most clinically relevant.

The use of human factors methods to identify and mitigate safety issues in radiation therapy

International Nuclear Information System (INIS)

Chan, Alvita J.; Islam, Mohammad K.; Rosewall, Tara; Jaffray, David A.; Easty, Anthony C.; Cafazzo, Joseph A.

2010-01-01

Background and purpose: New radiation therapy technologies can enhance the quality of treatment and reduce error. However, the treatment process has become more complex, and radiation dose is not always delivered as intended. Using human factors methods, a radiotherapy treatment delivery process was evaluated, and a redesign was undertaken to determine the effect on system safety. Material and methods: An ethnographic field study and workflow analysis was conducted to identify human factors issues of the treatment delivery process. To address specific issues, components of the user interface were redesigned through a user-centered approach. Sixteen radiation therapy students were then used to experimentally evaluate the redesigned system through a usability test to determine the effectiveness in mitigating use errors. Results: According to findings from the usability test, the redesigned system successfully reduced the error rates of two common errors (p < .04 and p < .01). It also improved the mean task completion time by 5.5% (p < .02) and achieved a higher level of user satisfaction. Conclusions: These findings demonstrated the importance and benefits of applying human factors methods in the design of radiation therapy systems. Many other opportunities still exist to improve patient safety in this area using human factors methods.

Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

Science.gov (United States)

Nakanishi, Asako; Hakamada, Arata; Isoda, Ken-ichi; Mizutani, Hitoshi

2005-05-01

Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

Long-term efficacy and safety of prophylaxis with recombinant factor VIII in Chinese pediatric patients with hemophilia A: a multi-center, retrospective, non-interventional, phase IV (ReCARE) study.

Science.gov (United States)

Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Weiqun; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

2017-07-01

The first recombinant factor VIII (rFVIII) product was launched in China in 2007. However, until now, no study has been conducted to describe the efficacy and safety of prophylaxis with rFVIII in Chinese pediatric patients with hemophilia A (HA). To summarize the efficacy and safety data on prophylaxis with rFVIII in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained regular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers (HTCs) across China. The primary endpoints included reduction in annualized bleeding rate (ABR); the secondary endpoints included evaluation of joint function (number and sites of target joints) using Gilbert score and Hemophilia Joint Health Score (HJHS), quality of life (QoL) and factors affecting treatment choices. Safety assessment of rFVIII was also conducted. We analyzed a total of 183 male pediatric patients (mean age, 7.1 ± 4.23 years) who received prophylaxis between 1 November 2007 and 31 May 2013. Compared with baseline, prophylaxis with rFVIII significantly reduced overall annualized joint bleed rate (AJBR) (p < .001) and ABR (p < .001). Inhibitor formation was reported in 5 (2.7%) patients and hemarthrosis was reported in 1 patient. The mean number of target joints was positively related to age (p < .001) and weight (p = .003) at baseline. Responses from survey questionnaires reported that effective bleeding control, joint protection, improvement in quality of life, favorable medical insurance policies, and economic capability were reasons for choosing prophylaxis. Prophylaxis with rFVIII reduced bleeding and number of target joints, even with a low-dose regimen, in Chinese pediatric patients with HA. Other than the efficacy and safety, factors such as poor disease control, improved economic stability and stable financial support made prophylaxis as an attractive treatment option. ClinicalTrials.gov ID

Review Blood coagulation factor VIII

Indian Academy of Sciences (India)

Unknown

the development of inhibitors in patients with hemophilia A. 2. Lifespan. 2.1 FVIII gene .... intron 22 inversion is principally an error of DNA repli- cation during ..... Pittman D D, Wang J H and Kaufman R J 1992 Identification and functional ...

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

NARCIS (Netherlands)

Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

Directory of Open Access Journals (Sweden)

Szlachcic A

2016-08-01

Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

DEFF Research Database (Denmark)

Bladbjerg, E-M; Skouby, S O.; Andersen, L F

2002-01-01

BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

Wound infections after median sternotomy treated by VAC therapy, summary of results, and risk factor analysis.

Science.gov (United States)

Hulman, M; Bezak, B; Artemiou, P; Cikrai, R

2017-01-01

The aim of this study is to summarize results and analyze risk factors for the development of wound infection in heart surgery patients after median sternotomy. In this retrospective analysis with assessment of multiple risk factors, we examined 143 patients with infection after median sternotomy treated with VAC therapy from total of 4,650 patients operated in our department from 2012 to 2015. Total of 143 patients developed significant SSI treated by VAC therapy following cardiac surgery. Of these, only 14 patients developed DSWI and one patient was diagnosed with suspected osteomyelitis. BMI, female gender, and use of BIMA proved to be statistically significant risk factors in our study (p infection (p infection proved to be a significant prognostic factor for patients' outcome (p infection (Tab. 3, Ref. 30).

Una frontera casi invisible: los territorios al norte del Sistema Central en la Alta Edad Media (siglos VIII-XI

Directory of Open Access Journals (Sweden)

Iñaki MARTÍN VISO

2009-12-01

Full Text Available RESUMEN: Los territorios al norte del Sistema Central no estuvieron sujetos a un dominio por parte de una autoridad centralizada entre los siglos VIII a XI. Los instrumentos del poder central, en especial la tributación y la organización episcopal, se descompusieron tras el siglo VIII y asumieron un papel determinante las estructuras de poder local, las cuales deben ser el principal objeto de estudio. A partir de su análisis, se descubre un espacio fronterizo abierto, con un dominio político informal, que es invisible para los poderes centrales. Palabras clave: Poderes Locales. Sitios de Altura. Necrópolis. Frontera. Tributación. Mozárabes.ABSTRACT: The territories at the North of the Iberian Central System were not ruled by any central authority between eighth and eleventh centuries. The main tools of the central power, especially the tribute and the episcopal organization, were broken down after the 8th century and the structures of local power, which must be studied particularly, got a very influential role. The analysis discover an opened frontier area, with an informal political control, that is invisible from the perspective of the central power

Risk factors and periimplantitis in implant therapy. Narrative review

Directory of Open Access Journals (Sweden)

Francis Bravo

2013-12-01

Full Text Available Diseases involving tissue around the teeth and osseointegrated implants are the result of an interaction between some type of pathological agent (bacterial, viral, etc. and host immune response. These interactions can occur both in the dental tissues as those biomaterials which are introduced to attempt to correct some type of periodontal disease, the implant being a biocompatible substitute of the teeth is not free from this type of interaction often enrolled periodontal and peri-implant pathology. The peri-implantitis is a type of disease that results from this interaction, the risk factors and risk indicators of peri-implantitis are broad and complex. This article summarizes the multiple sources of information in the scientific literature to address in detail the aspects of the main risk factors and the peri-implantitis in the peri implant therapy.

Factors influencing the use of outcome measures in physical therapy practice.

Science.gov (United States)

Wedge, Frances M; Braswell-Christy, Jennifer; Brown, Cynthia J; Foley, Kathleen T; Graham, Cecilia; Shaw, Sharon

2012-02-01

Use of outcome measures in physical therapy practice is central to evaluating the effectiveness of treatment interventions, providing accountability and addressing quality of physical therapy programs. There is limited discussion on barriers and facilitators to using outcome measures in physical therapy practice. The purpose of this study was to identify factors that influence a physical therapist when deciding to use outcome measures in clinical practice. Participants were 21 physical therapists, seven each from skilled nursing facilities, outpatient clinics, and inpatient rehabilitation facilities. A grounded theory approach was used for interview and data collection. Common themes were determined from the data and a theory developed to explain the rationale behind physical therapists' decisions to use or not use outcome measures in clinical practice. Three overlapping themes related to (1) concepts of time, (2) knowledge, and (3) facility culture were indentified as factors influencing the use of outcome measures. A fourth encompassing theme, professionalism, identified the value placed on the use of outcome measures in practice. Data revealed that therapists require more information on the outcome measures available, and this information needs to be easily accessible within the workplace. Therapists value information generated by using outcome measures in the clinical setting, but need information on what measures are available and psychometric properties. Information must be easily accessible and measures easy to use. Newer graduates and recent learners have a foundation in the use of outcome measures, but more needs to be done in the clinic and through continuing education to promote increased use and understanding.

Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: a case report and review of the literature.

Science.gov (United States)

Elhennawy, Karim; Reda, Seif; Finke, Christian; Graul-Neumann, Luitgard; Jost-Brinkmann, Paul-Georg; Bartzela, Theodosia

2017-08-15

Hereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-containing protein 12 gene, which plays a role in the development of pain-sensing nerve cells. Our patient's family was included in Chen and colleagues' study. We performed a literature review of the PubMed library (January 1985 to December 2016) on hereditary sensory and autonomic neuropathy type I to VIII genetic disorders and their orofacial manifestations. This case report is the first to describe the oral manifestations, and their treatment, of the recently discovered hereditary sensory and autonomic neuropathy type VIII in the medical and dental literature. We report on the oral manifestations and dental management of an 8-month-old white boy with hereditary sensory and autonomic neuropathy-VIII over a period of 16 years. Our patient was homozygous for a mutation of PR domain-containing protein 12 gene and was characterized by insensitivity to pain and thermal stimuli, self-mutilation behavior, reduced sweat and tear production, absence of corneal reflexes, and multiple skin and bone infections. Oral manifestations included premature loss of teeth, associated with dental traumata and self-mutilation, severe soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary teeth, and mandibular osteomyelitis. The lack of scientific knowledge on hereditary sensory and autonomic neuropathy due to the rarity of the disease often results in a delay in diagnosis, which is of substantial importance for the prevention of many complications and symptoms. Interdisciplinary work of specialized medical and dental teams and development of a standardized treatment protocols are essential for the management of the disease. There are many knowledge gaps concerning the management of patients with hereditary sensory and autonomic neuropathy-VIII

Retsensioon : Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare. Peatoimetaja Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. 326 lk. / Mart Nutt

Index Scriptorium Estoniae

Nutt, Mart, 1962-

2004-01-01

Arvustus: Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare / peatoim. Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. - Lisatud: Ott Heinapuu tutvustav sõnum retsenseeritud väljaande kohta lk. 193. - Vt. ka: http://www.riigikogu.ee/rito/index.php?id=11357

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.

Impact of identifying factors which trigger bothersome tinnitus on the treatment outcome in tinnitus retraining therapy.

Science.gov (United States)

Molini, Egisto; Faralli, Mario; Calzolaro, Lucia; Ricci, Giampietro

2014-01-01

The aim of this work was to ascertain any differences in the effectiveness of rehabilitation therapy in relation to the presence or absence of a known negative reinforcement responsible for the tinnitus-related pathology. Between 1 January 2001 and 31 December 2008, we recruited 294 subjects suffering from incapacitating tinnitus and/or hyperacusis. The patients underwent tinnitus retraining therapy (TRT) according to the methods described by Jastreboff and Hazell [Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge, Cambridge University Press, 2004, pp 121-133]. We clinically assessed the presence or absence of known phenomena of associative learning, regarding the presence of adverse events temporally correlated with tinnitus and the treatment outcome. The separate analysis of the 2 subgroups shows a statistically significant difference in the improvement rate between the group with a known triggering factor and the group without a triggering factor, with a preponderance of the former with a 91% improvement rate versus approximately 56% for the latter. In our study, the inability to identify factors triggering bothersome tinnitus negatively affected the treatment outcome in TRT. © 2014 S. Karger AG, Basel.

In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

Science.gov (United States)

Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

1993-10-01

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

DEFF Research Database (Denmark)

Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

2003-01-01

, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...

Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy.

Science.gov (United States)

Zhao, Wang; Zheng, Xi-Long; Jiang, Ze-Nan; Liao, Xiao-Bo; Zhao, Shui-Ping

2017-12-01

This study investigated the prevalence of atherogenic dyslipidemia (AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C) levels reached the goals with statin monotherapy and evaluated the characteristics of these patients. An analysis of the Dyslipidemia International Survey-China study that was carried out at 122 hospitals in China. Among patients reaching their LDL-C goals, the presence of AD was defined as triglyceride levels ≥1.7mmol/L and/or low levels of high-density lipoprotein cholesterol (men: dyslipidemia, 13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. The intensity of statin therapy did not affect the prevalence of AD. There was a high prevalence of AD in Chinese patients with optimal statin treatment. Some risk factors associated with AD were identified, but these factors were slightly different according to two criteria/guidelines. The intensity of statin therapy did not reduce the prevalence of AD. A combination lipid therapy may be more suitable for Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

Science.gov (United States)

Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Analysis of influence of dosimetric factors on the outcome of I-131 therapy in patients with hyperthyroidism

International Nuclear Information System (INIS)

Knapska-Kucharska, M.; Oszukowska, L.; Makarewicz, J.; Lewinski, A.

2012-01-01

The influence of dosimetric factors on the outcome of 131 I therapy has been examined in hyperthyroid patients submitted to 131 I treatment. The following factors - which could have influence on the effects of therapy with radioiodine - were analysed: the goitre volume, the thyroid radioiodine uptake after 24 h, and the effective half-life time of 131 I (EHL). Five hundred (500) randomly selected patients with hyperthyroidism, treated with 131 I, were studied. They were divided into three groups (based on clinical examination, hormonal and immunological tests, thyroid scintigraphy and ultrasound imaging). The study shows that the effectiveness of 131 I therapy depends on the thyroid volume and absorbed dose in all the groups of patients and on the thyroid radioiodine uptake and EHL in patients with a single autonomously functioning thyroid nodule. We have failed to determine the borderline D, distinguishing between effective and ineffective therapy. The treatment outcome can be predicted with approximately 70% accuracy, based on minimal absorbed dose

Analysis of influence of dosimetric factors on the outcome of I-131 therapy in patients with hyperthyroidism

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Knapska-Kucharska, M.; Oszukowska, L.; Makarewicz, J. [Department of Nuclear Medecine and Oncological Endocrinology, Province Hospital, Zgierz (Poland); Lewinski, A. [Chair and Department of Endocrinology and Metabolic Diseases, Medical University, Lodz (Poland)

2012-07-01

The influence of dosimetric factors on the outcome of {sup 131}I therapy has been examined in hyperthyroid patients submitted to {sup 131}I treatment. The following factors - which could have influence on the effects of therapy with radioiodine - were analysed: the goitre volume, the thyroid radioiodine uptake after 24 h, and the effective half-life time of {sup 131}I (EHL). Five hundred (500) randomly selected patients with hyperthyroidism, treated with {sup 131}I, were studied. They were divided into three groups (based on clinical examination, hormonal and immunological tests, thyroid scintigraphy and ultrasound imaging). The study shows that the effectiveness of {sup 131}I therapy depends on the thyroid volume and absorbed dose in all the groups of patients and on the thyroid radioiodine uptake and EHL in patients with a single autonomously functioning thyroid nodule. We have failed to determine the borderline D, distinguishing between effective and ineffective therapy. The treatment outcome can be predicted with approximately 70% accuracy, based on minimal absorbed dose

Measurements of the ground-state ionization energy and wavelengths for the 1snp 1P1*-1s21S0 (n=4-9) lines of Mg XI and F VIII

International Nuclear Information System (INIS)

Pal'chikov, V.G.; Ya Faenov, A.; Yu Skobelev, I.

2002-01-01

The wavelengths of the 1snp 1 P 1 0 -1s 2 1 S 0 transitions in the He-like Mg XI (n = 4-9) and F VIII (n=4-8) have been measured in laser-produced plasmas. The accuracy of the present measurements (0.4-1.6 mA) is a large improvement over previous results. The Rydberg series is used to determine the ground-state ionization energy of F VIII and Mg XI: E i on (F VIII) 953.96±0.11 eV, E i on (Mg XI)=1761.88±0.15 eV. These experimental results are compared with theoretical data calculated by the 1/Z-expansion method and the HFR and MCDF approaches. Fairly good agreement between theory and experiment is observed with a precision up to 5x10 -5 . Radiative corrections to the 1s 2 1 S 0 state are analysed and compared with experiments. It is found that QED corrections to the ground-state ionization energy are significant at the present level of experimental accuracy. (author)

MENINGKATKAN TANGGUNG JAWAB SOSIAL SISWA KELAS VIII MELALUI LAYANAN BIMBINGAN KELOMPOK

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Ummi Farikhatun Nisa

2012-12-01

Full Text Available The purpose of this research was to determine the efforts and success in improving students' social responsibility through group counseling services. Type of research used action research. Subjects were 12 students who had low social responsibility and being. Data collection technique used were psychological scales and observation. Data analysis techniques used are non-parametric statistics with the Wilcoxon test. Based on the calculations for the Wilcoxon test, a small amount of levels or Z value was 78.0. While Ztabel for n = 12 with an error level of 5% value is 14. So Z 78.0> 14.0 Ztabel or imply hypothesis accepted. These results demonstrate social responsibility of students prior to obtaining counseling services group at 51.93% (low. After following the guidance services at 81.51% (high. Conclusions from this research is a social responsibility to the students of class VIII SMP Putra Bangsa Bantarkawung increase after getting tutoring services group.

Psychological factors addressed in cognitive behaviour therapy for paediatric functional abdominal pain: Which are most important to target?

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van der Veek, Shelley M. C.; de Haan, Else; Derkx, H. H. F.; Benninga, Marc A.; Boer, Frits

2017-01-01

The effectiveness of cognitive behaviour therapy for paediatric functional abdominal pain leaves room for improvement. We studied which factors addressed in cognitive behaviour therapy relate most strongly to the physical and psychological functioning of children with functional abdominal pain and

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

DEFF Research Database (Denmark)

Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

2003-01-01

OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, ...

Risk Factors for Cataract After Palladium-103 Ophthalmic Plaque Radiation Therapy

International Nuclear Information System (INIS)

Finger, Paul T.; Chin, Kimberly J.; Yu Guopei; Patel, Neil S.

2011-01-01

Purpose: To examine how tumor characteristics and dose affect cataract development after plaque radiation therapy. Methods and Materials: Three hundred and eighty-four patients were diagnosed with uveal melanoma and treated with palladium-103 ( 103 Pd) plaque radiation therapy. Of these, 282 (74%) inclusion met exclusion criteria for follow-up time, tumor location, and phakic status. Then patient-, ophthalmic-, and radiation-specific factors (patient age, diabetes, hypertension, tumor location, tumor dimensions, and lens dose) were examined (by a Cox proportional regression model) as predictors for the development of radiation-related cataract. Results: Radiation cataract developed in 76 (24%) of patients at a mean follow-up of 39.8 months (range, 1-192). Patients with anteriorly located tumors were noted to have a higher incidence of cataract at 43.0% (43 of 100 patients) vs. 18.1% (33 cataracts per 182 patients) for posteriorly located tumors (p <0.0001). However, multivariate Cox proportional modeling showed that increasing patient age at time of treatment (p for trend = 0.0003) and higher lens dose (p for trend = 0.001) were the best predictors (biomarkers) for radiation cataract. Conclusions: Although anterior tumor location, greater tumor height, and increased patient age (at treatment) were associated with significantly greater risk for radiation cataract, dose to lens was the most significant factor.

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

Science.gov (United States)

Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

2007-10-01

A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

Hubungan Self-esteem dan Penggunaan Media Sosial Instagram dengan Perilaku Narsisme di Kalangan Siswa Kelas VIII Smpk Penabur Bintaro Jaya

OpenAIRE

Wibowo, Yonatan; Silaen, Sondang Maria J

2018-01-01

Tujuan dari penelitian ini adalah untuk mengetahui ada tidaknya hubungan self-esteem dan penggunaanmedia sosial Instagram dengan perilaku narsisme di kalangan siswa kelas VIII SMPK Penabur Bintaro Jaya.Dalam penelitian ini terdapat tiga variabel, yaitu perilaku narsisme sebagai variabel terikat serta self-esteem danpenggunaan media sosial Instagram sebagai variabel bebas. Sampel dalam penelitian ini adalah siswa kelasdelapan tahun pelajaran 2016/2017. Teknik pengambilan sampel dalam penelitia...

In vivo genome editing of the albumin locus as a platform for protein replacement therapy

Science.gov (United States)

Sharma, Rajiv; Anguela, Xavier M.; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C.; Sproul, Scott; Paschon, David E.; Miller, Jeffrey C.; Davidson, Robert J.; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D.; Holmes, Michael C.; Rebar, Edward J.

2015-01-01

Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) –mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. PMID:26297739

Bleeding and asymptomatic overdose in patients under Vitamin K antagonist therapy: Frequency and risk factors

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F. Ben Mbarka

2018-03-01

Full Text Available Background: Vitamin K antagonists are widely used in the treatment and prevention of thromboembolic disease. However, these drugs can cause serious side effects, especially bleeding. This study aims to evaluate frequency and risk factors of both bleeding and asymptomatic overdose in North African patients undergoing Vitamin K antagonist therapy. Methods: We performed a cross-sectional study in patients undergoing Vitamin K antagonist therapy. A statistical analysis has been conducted to identify overdose and bleeding risk factors by using chi-square test (p < .05. Results: One hundred and eleven patients were included. We recorded 14 cases of bleeding and 26 cases of asymptomatic overdose. Advanced age, poor adherence, concomitant use of paracetamol and history of previous bleeding are significant risk factors of over-anticoagulation. An INR value over 6 at admission, a high therapeutic target range for INR, concomitant use of acetylsalicylic acid, lack of information on overdose signs and measures to be taken in case of bleeding were identified as risk factors for bleeding. Conclusion: Most of the risk factors identified in our study seem to be related to patients lack of information and education. These results highlight the importance of creating a therapeutic patient education program. Keywords: Vitamin K antagonist, Bleeding, Risk factor, Overdose

Factors influencing the degree and pattern of parental involvement in play therapy for sexually abused children.

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Hill, Andrew

2009-01-01

Although much has been written about the role of therapists in children's recovery from child sexual abuse, relatively little attention has been paid to the role of nonoffending parents. This study investigated the work of a team of therapists who sometimes included such parents in therapy sessions with children. The study sought to understand what factors were influencing the degree and pattern of parental involvement and to understand what effect these patterns of parental involvement were having on the process and outcomes of therapy. The study successfully identified a range of factors influencing the patterns of parental involvement, but more research will be needed to understand the effect on outcomes.

Change Factors in the Process of Cognitive-Behavioural Therapy for Obsessive-Compulsive Disorder.

Science.gov (United States)

Schwartz, C; Hilbert, S; Schubert, C; Schlegl, S; Freyer, T; Löwe, B; Osen, B; Voderholzer, U

2017-05-01

While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd.

Il ruolo di El Escorial, V.III.6 e dei suoi discendenti nella tradizione manoscritta del Lucullus

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Corinna Senore

2017-05-01

Full Text Available L’articolo riguarda un gruppo di sette codici che tramanda il testo del Lucullus di Cicerone e che appartiene al ramo della tradizione discendente dal manoscritto Wien, Österreichische Nationalbibliothek 189. I sette manoscritti costituiscono uno stadio della tradizione caratterizzato dalla presenza di tre lacune testuali. Sulla base di alcuni elementi paleografici e della presenza di una glossa riportata a margine del testo di uno di essi, El Escorial, V.III.6 (Scor4, e inglobata all’interno del testo degli altri sei, è possibile individuare in Scor4 il capostipite di questo gruppo della tradizione. Lo studio si occupa inoltre di fare chiarezza sui rapporti che intercorrono tra i sei discendenti di Scor4. The article focuses on a group of seven codices which carry the text of Cicero’s Lucullus. This group belongs to the branch of the tradition descending from the manuscript Wien, Österreichische Nationalbibliothek 189. The seven manuscripts represent a step of the tradition marked by the presence of some textual lacunas. I start from some paleographic elements and from the presence of a gloss on text’s margin of one of them, El Escorial, V.III.6 (Scor4. The gloss has been then incorporated in the text of the other six manuscripts and I assume that Scor4 is the founder of this group of tradition. Furthermore, this article aims to clarify the relations between the six descendants of Scor4.

The factors affecting effectiveness of treatment in phages therapy, mini review

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Mai Huong eCHATAIN-LY

2014-02-01

Full Text Available In recent years, the use of lytic bacteriophages as antimicrobial agents controlling pathogenic bacteria has appeared as a promising new alternative strategy in the face of growing antibiotic resistance which has caused problems in many fields including medicine, veterinary medicine and aquaculture. The use of bacteriophages has numerous advantages over traditional antimicrobials. The effectiveness of phage applications in fighting against pathogenic bacteria depends on several factors such as the bacteriophages/target bacteria ratio, the mode and moment of treatment, environmental conditions (pH, temperature ..., the neutralization of phage and accessibility to target bacteria, amongst others. This report presents these factors and the challenges involved in developing phage therapy applications

Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

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Huang Xu

2010-08-01

Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

Therapies based on inhibitors of the epidermal growth factor receptor: enclosing the future

International Nuclear Information System (INIS)

Diaz, Arlhee; Lage, Agustin

2007-01-01

The Epidermal Growth Factor Receptor (EGFR) is considered an important target for rational drug design due to its key role in numerous tumors. Potential contribution of EGFR-related signaling pathways to promote tumorigenic processes, including cell proliferation, angiogenesis, and resistance to apoptosis has been well established. Two classes of anti-EGFR agents in late-stage clinical testing include monoclonal antibodies against extracellular EGFR domain (Cetuximab, Nimotuzumab) and small molecules tyrosine kinase inhibitors, which inhibit the receptor enzyme activity (Gefitinib, Erlotinib). A considerable body of evidence has emerged since its introduction in the treatment of cancer patients. However, important questions such as reliable surrogate markers to predict response to the treatment, or optimal sequence and combination of these agents with conventional therapies remain to be addressed. Identify and validate predictive factors to select patients likely to respond to EGFR inhibitors, such as mutations that confer resistance versus those associated with sensitivity is required. A better understanding of molecular mechanisms associated with antitumor activity will useful to predict the interaction of these agents with other therapies in order to avoid antagonisms or overlapping effects resulting in no adding effects. Finally, the benefits derived from EGFR inhibitors as first-line therapy in selected populations, and the optimal doses and ways to delivery to the tumor site resulting in optimal target modulation should be established by the ongoing investigation. (Author)

Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of combination antiretroviral therapy: a European multicohort study

DEFF Research Database (Denmark)

Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique

2009-01-01

Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART).......Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART)....

Love and/in psychoanalysis: a commentary on Lacan's reading of Plato's Symposium in Seminar VIII: Transference.

Science.gov (United States)

Fink, Bruce

2015-02-01

What is love and what part does it play in psychoanalysis? Where are the analyst and the analysand situated in relation to the roles defined as those of the "lover" and the "beloved"? Jacques Lacan explores these and other questions in his soon-to-be-published Seminar VIII: Transference by providing an extensive commentary on Plato's most famous dialogue on love, the Symposium. This paper outlines some of the major points about love that grow out of Lacan's reading of the dialogue and examines their relevance to the analytic setting. Can the analyst be characterized as a sort of modern-day Socrates?

The Provision of Psychological Therapy to People with Intellectual Disabilities: An Investigation into Some of the Relevant Factors

Science.gov (United States)

Mason, J.

2007-01-01

Background: Five factors are proposed as important in influencing the provision of psychological therapy to people with intellectual disabilities (IDs): the perceived effectiveness of psychological therapy, individual clinician competence, service resources (number of trained clinicians), the level of the clients disability and the diagnostic…

Identifying Predictive Factors for Incident Reports in Patients Receiving Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Elnahal, Shereef M., E-mail: selnaha1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Smith, Koren; Souranis, Annette N.; Briner, Valerie; McNutt, Todd R.; DeWeese, Theodore L.; Wright, Jean L.; Terezakis, Stephanie A. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2016-04-01

Purpose: To describe radiation therapy cases during which voluntary incident reporting occurred; and identify patient- or treatment-specific factors that place patients at higher risk for incidents. Methods and Materials: We used our institution's incident learning system to build a database of patients with incident reports filed between January 2011 and December 2013. Patient- and treatment-specific data were reviewed for all patients with reported incidents, which were classified by step in the process and root cause. A control group of patients without events was generated for comparison. Summary statistics, likelihood ratios, and mixed-effect logistic regression models were used for group comparisons. Results: The incident and control groups comprised 794 and 499 patients, respectively. Common root causes included documentation errors (26.5%), communication (22.5%), technical treatment planning (37.5%), and technical treatment delivery (13.5%). Incidents were more frequently reported in minors (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to have incidents. Conclusions: We found several treatment- and patient-specific variables associated with incidents. These factors should be considered by treatment teams at the time of peer review to identify patients at higher risk. Larger datasets are required to recommend changes in care process standards, to minimize safety risks.

Identifying Predictive Factors for Incident Reports in Patients Receiving Radiation Therapy

International Nuclear Information System (INIS)

Elnahal, Shereef M.; Blackford, Amanda; Smith, Koren; Souranis, Annette N.; Briner, Valerie; McNutt, Todd R.; DeWeese, Theodore L.; Wright, Jean L.; Terezakis, Stephanie A.

2016-01-01

Purpose: To describe radiation therapy cases during which voluntary incident reporting occurred; and identify patient- or treatment-specific factors that place patients at higher risk for incidents. Methods and Materials: We used our institution's incident learning system to build a database of patients with incident reports filed between January 2011 and December 2013. Patient- and treatment-specific data were reviewed for all patients with reported incidents, which were classified by step in the process and root cause. A control group of patients without events was generated for comparison. Summary statistics, likelihood ratios, and mixed-effect logistic regression models were used for group comparisons. Results: The incident and control groups comprised 794 and 499 patients, respectively. Common root causes included documentation errors (26.5%), communication (22.5%), technical treatment planning (37.5%), and technical treatment delivery (13.5%). Incidents were more frequently reported in minors (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to have incidents. Conclusions: We found several treatment- and patient-specific variables associated with incidents. These factors should be considered by treatment teams at the time of peer review to identify patients at higher risk. Larger datasets are required to recommend changes in care process standards, to minimize safety risks.

3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

International Nuclear Information System (INIS)

Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

2011-01-01

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

DEFF Research Database (Denmark)

Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

2003-01-01

, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...... therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette...

20 CFR 404.535 - How much will we withhold from your title VIII and title XVI benefits to recover a title II...

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How much will we withhold from your title... Officer § 404.535 How much will we withhold from your title VIII and title XVI benefits to recover a title II overpayment? (a) If past-due benefits are payable to you, we will withhold the lesser of the...

Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy

NARCIS (Netherlands)

van der Meer, Marrit; Hoving, Jan L.; Vermeulen, Marjolein I. M.; Herenius, Marieke M. J.; Tak, Paul P.; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

2011-01-01

To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with

Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

DEFF Research Database (Denmark)

Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

2016-01-01

BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...

Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

DEFF Research Database (Denmark)

Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

2010-01-01

Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

The Funnel Geometry of Open Flux Tubes in the Low Solar Corona Constrained by O VI and Ne VIII Outflow

Science.gov (United States)

Byhring, Hanne S.; Esser, Ruth; Lie-Svendsen, Oystein

2008-01-01

Model calculations show that observed outflow velocities of order 7-10 km/s of C IV and O VI ions, and 15-20 km/s of Ne VIII ions, are not only consistent with models of the solar wind from coronas holes, but also place unique constraints on the degree of flow tube expansion as well as the location of the expansion in the transition region/lower corona.

Childhood urinary tract infection caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and empiric therapy.

Science.gov (United States)

Uyar Aksu, Nihal; Ekinci, Zelal; Dündar, Devrim; Baydemir, Canan

2017-02-01

This study investigated risk factors of childhood urinary tract infection (UTI) associated with extended-spectrum β-lactamase (ESBL)-producing bacteria (ESBL-positive UTI) and evaluated antimicrobial resistance as well as empiric treatment of childhood UTI. The records of children with positive urine culture between 1 January 2008 and 31 December 2012 were evaluated. Patients with positive urine culture for ESBL-producing bacteria were defined as the ESBL-positive group, whereas patients of the same gender and similar age with positive urine culture for non-ESBL-producing bacteria were defined as the ESBL-negative group. Each ESBL-positive patient was matched with two ESBL-negative patients. The ESBL-positive and negative groups consisted of 154 and 308 patients, respectively. Potential risk factors for ESBL-positive UTI were identified as presence of underlying disease, clean intermittent catheterization (CIC), hospitalization, use of any antibiotic and history of infection in the last 3 months (P infection in the last 3 months were identified as independent risk factors. In the present study, 324 of 462 patients had empiric therapy. Empiric therapy was inappropriate in 90.3% of the ESBL-positive group and in 4.5% of the ESBL-negative group. Resistance to nitrofurantoin was similar between groups (5.1% vs 1.2%, P = 0.072); resistance to amikacin was low in the ESBL-positive group (2.6%) and there was no resistance in the ESBL-negative group. Clean intermittent catheterization, hospitalization and history of infection in the last 3 months should be considered as risk factors for ESBL-positive UTI. The combination of ampicillin plus amikacin should be taken into consideration for empiric therapy in patients with acute pyelonephritis who have the risk factors for ESBL-positive UTI. Nitrofurantoin seems to be a logical choice for the empiric therapy of cystitis. © 2016 Japan Pediatric Society.

Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

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Mridula Krishnan

2017-08-01

Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

Science.gov (United States)

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

2008-12-01

To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

Application of stem cell/growth factor system, as a multimodal therapy approach in regenerative medicine to improve cell therapy yields.

Science.gov (United States)

Pourrajab, Fatemeh; Babaei Zarch, Mojtaba; Baghi Yazdi, Mohammad; Rahimi Zarchi, Abolfazl; Vakili Zarch, Abbas

2014-04-15

Stem cells hold a great promise for regenerative medicine, especially for replacing cells in infarcted organ that hardly have any intrinsic renewal capacity, including heart and brain. Signaling pathways that regulate pluripotency or lineage-specific gene and protein expression have been the major focus of stem cell research. Between them, there are some well known signaling pathways such as GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines may regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes or accentuate synergistic compliance. For example, contributing factors in the progression of heart failure are both the loss of cardiomyocytes after myocardial infarction, and the absence of an adequate endogenous repair signaling. Combining cell engraftment with therapeutic signaling factor delivery is more exciting in terms of host progenitor/donor stem cell survival and proliferation. Thus stem cell-based therapy, besides triggering signaling pathways through GF/GFR systems can become a realistic option in regenerative processes for replacing lost cells and reconstituting the damaged organ, as before. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos Use of recombinant activated factor VII for treatment and prophylaxis of major bleeding

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Flávio Augusto Henriques Vince

2009-09-01

pacientes. Dessa forma, o recente aumento do uso de rFVIIa em situações ainda não aprovadas levou ao crescente questionamento sobre eficácia e segurança desta específica medicação em tais situações.INTRODUCTION: Recombinant activated factor VII (rFVIIa is a protein produced by genetic engineering, the structure is very similar to the structure of intrinsic activated factor VII (FVII. Its action is based on knowledge of the coagulation mechanism in vivo by acting in direct activation of factor X independent resulting in formation of thrombin at the injury site and thereby contributing to the formation of stable fibrin clots without the action of factor VIII and factor IX. METHODS: Was conducted extensive review of the literature in order to determine the new findings related to the use of recombinant activated factor VII in patients with severe bleeding. RESULTS: It was found that the use of rFVIIa started in the 80's for prophylaxis and treatment of bleeding in patients with a history of hemophilia A or B with inhibitors to factor VIII and IX, factor VII deficiency and Glanzmann's thrombasthenia refractory to replacement platelet. In 1999 its use was expanded to other clinical situations and thus began to be published several studies showing the efficacy of rFVIIa as a pro-hemostatic agent in patients with bleeding disorders or other previously healthy patients with a history of acute bleeding of major consequence. Trauma is the leading cause of mortality worldwide and uncontrolled bleeding the main challenge in caring for these patients. It is common for the association of trauma with coagulopathy, requiring in some cases specific therapy to treat it. At this point in adjuvant therapy with rFVIIa should be considered. Other common causes of bleeding are the heart, gynecologic/obstetric surgeries and diseases involving the liver. The coagulopathy in these cases is deficiency of factors dependent on vitamin K, and the FVII factor with smaller half life. CONCLUSION

Factors related to attrition from trauma-focused cognitive behavioral therapy.

Science.gov (United States)

Wamser-Nanney, Rachel; Steinzor, Cazzie E

2017-04-01

Attrition from child trauma-focused treatments such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is common; yet, the factors of children who prematurely terminate are unknown. The aim of the current study was to identify risk factors for attrition from TF-CBT. One hundred and twenty-two children (ages 3-18; M=9.97, SD=3.56; 67.2% females; 50.8% Caucasian) who received TF-CBT were included in the study. Demographic and family variables, characteristics of the trauma, and caregiver- and child-reported pretreatment symptoms levels were assessed in relation to two operational definitions of attrition: 1) clinician-rated dropout, and 2) whether the child received an adequate dose of treatment (i.e., 12 or more sessions). Several demographic factors, number of traumatic events, and children's caregiver-rated pretreatment symptoms were related to clinician-rated dropout. Fewer factors were associated with the adequate dose definition. Child Protective Services involvement, complex trauma exposure, and child-reported pretreatment trauma symptoms were unrelated to either attrition definition. Demographics, trauma characteristics, and level of caregiver-reported symptoms may help to identify clients at risk for premature termination from TF-CBT. Clinical and research implications for different operational definitions and suggestions for future work will be presented. Published by Elsevier Ltd.

Effectiveness of Adaptive Contextual Learning Model of Integrated Science by Integrating Digital Age Literacy on Grade VIII Students

Science.gov (United States)

Asrizal, A.; Amran, A.; Ananda, A.; Festiyed, F.

2018-04-01

Educational graduates should have good competencies to compete in the 21st century. Integrated learning is a good way to develop competence of students in this century. Besides that, literacy skills are very important for students to get success in their learning and daily life. For this reason, integrated science learning and literacy skills are important in 2013 curriculum. However, integrated science learning and integration of literacy in learning can’t be implemented well. Solution of this problem is to develop adaptive contextual learning model by integrating digital age literacy. The purpose of the research is to determine the effectiveness of adaptive contextual learning model to improve competence of grade VIII students in junior high school. This research is a part of the research and development or R&D. Research design which used in limited field testing was before and after treatment. The research instruments consist of three parts namely test sheet of learning outcome for assessing knowledge competence, observation sheet for assessing attitudes, and performance sheet for assessing skills of students. Data of student’s competence were analyzed by three kinds of analysis, namely descriptive statistics, normality test and homogeneity test, and paired comparison test. From the data analysis result, it can be stated that the implementation of adaptive contextual learning model of integrated science by integrating digital age literacy is effective to improve the knowledge, attitude, and literacy skills competences of grade VIII students in junior high school at 95% confidence level.

Evaluation of the integrity of reactor vessels designed to ASME Code, Sections I and/or VIII

International Nuclear Information System (INIS)

Hoge, K.G.

1976-01-01

A documented review of nuclear reactor pressure vessels designed to ASME Code, Sections I and/or VIII is made. The review is primarily concerned with the design specifications and quality assurance programs utilized for the reactor vessel construction and the status of power plant material surveillance programs, pressure-temperature operating limits, and inservice inspection programs. The following ten reactor vessels for light-water power reactors are covered in the report: Indian Point Unit No. 1, Dresden Unit No. 1, Yankee Rowe, Humboldt Bay Unit No. 3, Big Rock Point, San Onofre Unit No. 1, Connecticut Yankee, Oyster Creek, Nine Mile Point Unit No. 1, and La Crosse

Understanding the first Neolithic occupation of Cova d'En Pardo (Planes, Alicante: Preliminary results of the multidisciplinary analysis of levels VIII and VIIIB

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Jorge Agatángelo Soler Díaz

2014-01-01

Full Text Available We present the results of excavations carried out in the Cova d'En Pardo (Planes, Alicante, specifically the levels VIII and VIIIb. The development of a multidisciplinary project has allowed to us characterize the occupation of a small cavity by the first farming communities associated with the Neolithization process of the east of Iberian Peninsula.

Detection of hemophilia A carriers by use of frozen plasma samples

International Nuclear Information System (INIS)

Yang, H.C.; Hardin, J.; Vaudreuil, C.

1978-01-01

The efficacy of using promptly frozen plasma samples in the diagnosis of the carrier state for hemophilia A was evaluated by simultaneous measurement of factor VIII activity and antigen in 20 normal women and 20 obligate carriers. Factor VIII antigen was measured by two methods, electroimmunoassay and immunoradiometric assay. When the factor VIII activity and antigen data were evaluated by regression analysis, 94% of the carriers were correctly identified at the 95% confidence level

Hypoxia-Inducible Factor-1 in Physiological and Pathophysiological Angiogenesis: Applications and Therapies

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Zimna, Agnieszka; Kurpisz, Maciej

2015-01-01

The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy. PMID:26146622

Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy

Energy Technology Data Exchange (ETDEWEB)

Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

2017-02-15

Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed. Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn't change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO{sub 2} in the blood (pCO{sub 2}) was increased and pO{sub 2} was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1. DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant. (orig.) [German] Patientenbezogene, therapiebezogene und Lungenfunktionsdaten (''pulmonary function test'', PFT) wurden vor Radiotherapie (RT) und an verschiedenen Nachsorgeterminen nach RT prospektiv gesammelt, um PFT-Veraenderungen sowie Einflussfaktoren nach Hochdosis-Radio(chemo)therapie zu

Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats

International Nuclear Information System (INIS)

Kane, W.H.; Ichinose, A.; Hagen, F.S.; Davie, E.W.

1987-01-01

Human factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor X/sub a/. Prior to its participation in the coagulation cascade, factor V is converted to factor V/sub a/ by thrombin generating a heavy chain and a light chain, and these two chains are held together by calcium ions. A connecting region originally located between the heavy and light chains is liberated during the activation reaction. In a previous study, a cDNA of 2970 nucleotides that codes for the carboxyl-terminal 938 amino acids of factor V was isolated and characterized from a Hep G2 cDNA library. This cDNA has been used to obtain additional clones from Hep G2 and human liver cDNA libraries. Furthermore, a Hep G2 cDNA library prepared with an oligonucleotide from the 5' end of these cDNAs was screened to obtain overlapping cDNA clones that code for the amino-terminal region of the molecule. The composite sequence of these clones spans 6911 nucleotides and is consistent with the size of the factor V message present in Hep G2 cells (approximately 7 kilobases). The cDNA codes for a leader sequence of 28 amino acids and a mature protein of 2196 amino acids. The amino acid sequence predicted from the cDNA was in complete agreement with 139 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the heavy chain region and connecting region of plasma factor V. The domain structure of human factor V is similar to that previously reported for human coagulation factor VIII. Two types of tandem repeats (17 and 9 amino acids) have also been identified in the connecting region of factor V. The present data indicate that the amino acid sequence in the heavy and light chain regions of factor V is ∼ 40% identical with the corresponding regions of factor VIII

Seleucid, Demotic and Mediterranean mathematics versus Chapters VIII and IX of the Nine Chapters: accidental or significant similarities?

DEFF Research Database (Denmark)

Høyrup, Jens

Similarities of geometrical diagrams and arithmetical structures of problems have often been taken as evidence of transmission of mathematical knowledge or techniques between China and “the West”. Confronting on one hand some problems from Chapter VIII of the Nine Chapters with comparable problems...... known from Ancient Greek sources, on the other a Seleucid collection of problems about rectangles with a subset of the triangle problems from Chapter IX, it is concluded, (1) that transmission of some arithmetical riddles without method – not “from Greece” but from a transnational community of traders...

Pelvic haemophilic pseudotumour: management of a patient with high level of inhibitors

International Nuclear Information System (INIS)

Keller, A.; Terrier, F.; Schneider, P.A.; Bianchi, S.; Howarth, N.; De Moerloose, P.

2002-01-01

Haemophilic pseudotumour (HP) is a rare but very serious complication of haemophilia. HP affects mainly patients with severe haemophilia and those who have developed antibodies to factor VIII or factor IX. We report on a 45-year-old man with haemophilia A and high titres of inhibitors who developed an extensive HP with progressive destruction of the right ilium over a period of 12 years. The different therapeutic options (conservative management by replacement therapy, surgical approach, radiotherapy, percutaneous evacuation with secondary refilled cavity and transcatheter arterial embolization) are reviewed. (orig.)

Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

International Nuclear Information System (INIS)

Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

1990-01-01

A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

Risk Factors for High-Titer Inhibitor Development in Children with Hemophilia A: Results of a Cohort Study

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Susan Halimeh

2013-01-01

Full Text Available Among the discussed risk factors for high-titre inhibitor (HRI development in patients with hemophilia A (HA are high dose FVIII replacement therapy and use of recombinant FVIII concentrates (rFVIII. The aim of this study was to evaluate the aforementioned risk factors for HRI development in children with hemophilia A ≤2%. About 288 ascertained PUPs (Israel and Germany were followed after initial HA diagnosis over 200 exposure days. Inhibitor-free survival, hazard ratios (HR, and 95% confidence intervals (CIs were calculated. Adjustment was performed for factor VIII concentrates, median single dose over the first three months of treatment, first FVIII administration before the age of three months, presence of risk HA gene mutations, “intensive treatment moments” and “year of birth” (proxy for different treatment periods. HRI occurred in 71/288 children (24.7%. In multivariate analysis adjusted for “year of birth”, underlying risk gene mutations (HR/CI: 2.37/1.40–3.99, FVIII dose, measured per one IU increase per kgbw (HR/CI: 1.05/1.04–1.07, and first FVIII administration before the age of three months showed a significant impact on HR development. The risk of HRI development was similar for recombinant or plasmatic FVIII products. Children at risk should be treated with carefully calculated lower dose regimens, adapted to individual bleeding situations.

PENGARUH PENGGUNAAN VARIASI METODE DAN MODEL PEMBELAJARAN TERHADAP HASIL BELAJAR FISIKA SISWA KELAS VIII SMPN2 MARGATIGA SEMESTER GENAP TP 2013/2014

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Eni Fitriani

2015-03-01

Full Text Available The purpose of this study was to investigate the effect of variations in the methods and models of teaching to student learning outcomes VIII SMPN2 MARGA TIGA.This research is experimental research which ofdesign completely randomized or completely randomized experimental design.The population in thisresearch is all of student VIII class in SMPN 2 MARGA TIGA2013/2014. The sample in this research is VIIIth class which totaling 34 students.In this research, conducted with three treatments of learning in a classroom.Data collection techniques in this research use the technique of the test, which tests the end (posttest were then analyzed with the test results hipotesis. From posttest analysis results of hypothesis testing using one-way ANOVA test (Completely Randomized Design at the 5% significance level value obtained results Fobs = 1.5244 and Ftab = 3.10 this shows that H0 is accepted and means variety of methods and learning models provide a similar impact on student learning outcomes.It can be concluded that all three treatments had similar quality if tailored to the needs of all three materials. 

The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

Science.gov (United States)

El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

2013-09-05

The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

Analisis Deskriptif Soal Geometri dalam Buku Matematika Bilingual untuk Sekolah Menengah Pertama Kelas VIII Berdasarkan Kriteria International Assessment TIMSS 2007

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Etik Rahayu

2012-06-01

Full Text Available Tujuan penelitian ini adalah untuk mendeskripsikan  domain kognitif dan aspek kognitif (required behavior soal matematika dalam Buku Matematika Bilingual untuk Sekolah Menengah Pertama (SMP Kelas VIII berdasarkan kriteria International Assessment TIMSS 2007 dan proporsinya. Metode penelitian yang digunakan adalah deskriptif kualitatif, dengan subjek penelitian adalah soal geometri dalam Buku Matematika Bilingual SMP. yang berjudul “Mathematics for Junior High School Grade VIII 1st Semester” dan “Mathematics for Junior High School Grade VIII 2nd Semester” karangan karangan M. Cholik Adinawan dan Sugijono. Pengumpulan data menggunakan metode observasi dan wawancara tentang penggunaan buku matematika bilingual yang paling banyak digunakan di kota semarang. Pedoman analisis soal berdasarkan kriteria International Assessment TIMSS 2007, dengan validasi hasil oleh ahli. Hasil penelitian menunjukkan bahwa soal yang dianalisis memuat satu hingga tujuh aspek kognitif. Sebagian besar soal memuat 4 aspek kognitif yaitu 44.04 %, diikuti soal dengan 3 aspek kognitif  yaitu 36, 42%,  soal dengan 2 aspek kognitif yaitu 14, 90%, kemudian 1,99% untuk soal dengan 1 atau 5 aspek kognitif, dan 0,33% untuk soal dengan 6 atau 7 aspek kognitif. Proporsi tinggi pada recall (28.26% dan compute (26.57%, diikuti dengan SRP (10.85%, implement (10.65%, retrieve (8.36%, recognize (6.17%, analyze (1.99%, measure (1.59%, generalize (1.09%, SNRP (1.00%, classify (0.80%, represent (0.80%, justify (0.80%, select (0.60%, model (0.30%, synthesis (0.20%. Secara keseluruhan berdasarkan International Assessment TIMSS 2007 soal yang termasuk domain knowing memiliki persentase paling tinggi (52.28%, domain knowing-applying (24.83%, domain knowing- reasoning (12.91%, dan hanya sedikit yang termasuk domain knowing-apllying-reasoning (3.97%. Serta terdapat 4 soal (1.32% yang mempunyai ketidaksesuaian penggunaan mathematics terms serta 1 soal (0

Blood coagulation factor VIII: An overview

Indian Academy of Sciences (India)

Unknown

Solvent, detergent and heat treatment. Hemofil-M. Baxter. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal anti- body. Solvent and detergent. Monarc-M. American. Red Cross. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal antibody.

Hemofilia A adquirida Acquired hemophilia A

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Delfina Almagro Vázquez

2010-12-01

, extension of activated partial thromboplastin time (APTT, decrease of Factor VIII activity, and presence of Factor VIII inhibitors. AHA treatment includes the control of hemorrhagic manifestations and the suppression of antibody production. The recombinant factor VIIIa (rVIIIaF concentration and the prothrombin-complex concentrations (PCC are considered like the first-line antihemorrhagic treatment. As alternative therapy in some cases the FCIII concentration, the plasmapheresis and extracorporeal immuno-adsorption may be used. The prednisone alone or associated with cyclophosphamide is the firs-line immunosuppressive treatment. In refractory patients it may be administered as a second-line therapy, the Rituximab (anti-CD20. With the use of Azathioprine, Cyclosporine, Vincristine and the Mycophenolate mofetil variable results have been achieved.

Antibody response to recombinant human coagulation factor VIII in a new rat model of severe hemophilia A

DEFF Research Database (Denmark)

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

2016-01-01

Background: Neutralizing antibodies towardFVIII replacement therapy (inhibitors) are the most seri-ous treatment-related complication in hemophilia A(HA). A rat model of severe HA (F8/) has recentlybeen developed, but an immunological characterization isneeded to determine the value of using...

An examination of human factors in external beam radiation therapy: Findings and implications

International Nuclear Information System (INIS)

Henriksen, K.; Kaye, R.D.; Jones, R.E. Jr.; Morisseau, D.S.; Persensky, J.J.

1994-01-01

To better understand the contributing factors to human error in external beam radiation therapy, the US Nuclear Regulatory Commission has undertaken a series of human factors evaluations. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation technologists, conducted visits to 24 radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of human-system interfaces, procedures, training and qualifications, and organizational policies and practices. Representative findings and implications for improvement are discussed within the context of a dynamic model which holds that misadministration likely results from the unanticipated interaction of several necessary but singly insufficient conditions

Factors Affecting Hemodialysis Patients' Satisfaction with Their Dialysis Therapy

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M. Al Eissa

2010-01-01

Full Text Available Aim. To assess the degree of satisfaction among hemodialysis patients and the factors influencing this satisfaction. Methods. Patients were recruited from 3 Saudi dialysis centers. Demographic data was collected. Using 1 to 10 Likert scale, the patients were asked to rate the overall satisfaction with, and the overall impact of, their dialysis therapy on their lives and to rate the effect of the dialysis therapy on 15 qualities of life domains. Results. 322 patients were recruited (72.6% of the total eligible patients. The mean age was 51.7 years (±15.4; 58% have been on dialysis for >3 years. The mean Charlson Comorbidity Index was 3.2 (±2, and Kt/V was 1.3 (±0.44. The mean satisfaction score was (7.41 ± 2.75 and the mean score of the impact of the dialysis on the patients' lives was 5.32 ± 2.55. Male patients reported worse effect of dialysis on family life, social life, energy, and appetite. Longer period since the commencement of dialysis was associated with adverse effect on finances and energy. Lower level of education was associated with worse dialysis effect on stress, overall health, sexual life, hobbies, and exercise ability. Conclusion. The level of satisfaction is affected by gender, duration on dialysis, educational level, and standard of care given.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

2017-04-01

Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

On existence and properties of plutonium(VIII) derivatives

Energy Technology Data Exchange (ETDEWEB)

Kiselev, Yu.M.; Dolzhenko, V.D.; Ermilov, A.Yu. [Moscow State Univ. (Russian Federation). Chemistry Dept.; Nikonov, M.V.; Myasoedov, B.F. [Russian Academy of Science, Moscow (Russian Federation). Inst. of Geochemistry and Analytical Chemistry; Tananaev, I.G. [Russian Academy of Science, Moscow (Russian Federation). Inst. of Physical Chemistry and Electrochemistry

2014-04-01

The existence of Pu(VIII) was shown in alkaline solutions and in nonpolar solvents (CCl{sub 4} and CHCl{sub 3}) on the ground of such experimental facts like extraction of plutonium species, obtained by means of ozonization of Pu(VI) alkaline solutions into CCl{sub 4} and CHCl{sub 3}; volatility of Pu compounds out of aqueous alkaline solutions, and the mentioned solvents. The product of interaction between PuO{sub 3}.0.8H{sub 2}O and XeF{sub 2} in CCl{sub 4} and CHCl{sub 3} was of the same chemical form for both cases and identical with the form of the product of volatility of Pu out of these organic solutions. The electronic absorbance spectra of these products in CCl{sub 4} and CHCl{sub 3} were fairly similar to the ones for OsO{sub 4} and RuO{sub 4}. The band of absorption in these spectra with the maximum at 332 nm corresponds to the charge transfer of metal-ligand type [π(O)→Pu], as the value of molar extinction coefficient e was found to be higher than 2 x 10{sup 3} L/mole cm. A satisfactory agreement between the energies for the transitions of PuO{sub 4} molecule designed by X{sub α}-SW method and experimental data was observed. A similar accordance was observed for the designed vibration frequency (DFT-method) with the one found as result of analysis of the vibration structure of the experimental spectra. (orig.)

Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.

Science.gov (United States)

Chayama, Kazuaki; Hayes, C Nelson; Yoshioka, Kentaro; Moriwaki, Hisataka; Okanoue, Takashi; Sakisaka, Shotaro; Takehara, Tetsuo; Oketani, Makoto; Toyota, Joji; Izumi, Namiki; Hiasa, Yoichi; Matsumoto, Akihiro; Nomura, Hideyuki; Seike, Masataka; Ueno, Yoshiyuki; Yotsuyanagi, Hiroshi; Kumada, Hiromitsu

2011-04-01

Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy. We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment. When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%. Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

ENDF/B-VIII.0: The 8th Major Release of the Nuclear Reaction Data Library with CIELO-project Cross Sections, New Standards and Thermal Scattering Data

Science.gov (United States)

Brown, D. A.; Chadwick, M. B.; Capote, R.; Kahler, A. C.; Trkov, A.; Herman, M. W.; Sonzogni, A. A.; Danon, Y.; Carlson, A. D.; Dunn, M.; Smith, D. L.; Hale, G. M.; Arbanas, G.; Arcilla, R.; Bates, C. R.; Beck, B.; Becker, B.; Brown, F.; Casperson, R. J.; Conlin, J.; Cullen, D. E.; Descalle, M.-A.; Firestone, R.; Gaines, T.; Guber, K. H.; Hawari, A. I.; Holmes, J.; Johnson, T. D.; Kawano, T.; Kiedrowski, B. C.; Koning, A. J.; Kopecky, S.; Leal, L.; Lestone, J. P.; Lubitz, C.; Márquez Damián, J. I.; Mattoon, C. M.; McCutchan, E. A.; Mughabghab, S.; Navratil, P.; Neudecker, D.; Nobre, G. P. A.; Noguere, G.; Paris, M.; Pigni, M. T.; Plompen, A. J.; Pritychenko, B.; Pronyaev, V. G.; Roubtsov, D.; Rochman, D.; Romano, P.; Schillebeeckx, P.; Simakov, S.; Sin, M.; Sirakov, I.; Sleaford, B.; Sobes, V.; Soukhovitskii, E. S.; Stetcu, I.; Talou, P.; Thompson, I.; van der Marck, S.; Welser-Sherrill, L.; Wiarda, D.; White, M.; Wormald, J. L.; Wright, R. Q.; Zerkle, M.; Žerovnik, G.; Zhu, Y.

2018-02-01

We describe the new ENDF/B-VIII.0 evaluated nuclear reaction data library. ENDF/B-VIII.0 fully incorporates the new IAEA standards, includes improved thermal neutron scattering data and uses new evaluated data from the CIELO project for neutron reactions on 1H, 16O, 56Fe, 235U, 238U and 239Pu described in companion papers in the present issue of Nuclear Data Sheets. The evaluations benefit from recent experimental data obtained in the U.S. and Europe, and improvements in theory and simulation. Notable advances include updated evaluated data for light nuclei, structural materials, actinides, fission energy release, prompt fission neutron and γ-ray spectra, thermal neutron scattering data, and charged-particle reactions. Integral validation testing is shown for a wide range of criticality, reaction rate, and neutron transmission benchmarks. In general, integral validation performance of the library is improved relative to the previous ENDF/B-VII.1 library.

ENDF/B-VIII.0: The 8 th Major Release of the Nuclear Reaction Data Library with CIELO-project Cross Sections, New Standards and Thermal Scattering Data

Energy Technology Data Exchange (ETDEWEB)

Brown, D. A.; Chadwick, M. B.; Capote, R.; Kahler, A. C.; Trkov, A.; Herman, M. W.; Sonzogni, A. A.; Danon, Y.; Carlson, A. D.; Dunn, M.; Smith, D. L.; Hale, G. M.; Arbanas, G.; Arcilla, R.; Bates, C. R.; Beck, B.; Becker, B.; Brown, F.; Casperson, R. J.; Conlin, J.; Cullen, D. E.; Descalle, M. -A.; Firestone, R.; Gaines, T.; Guber, K. H.; Hawari, A. I.; Holmes, J.; Johnson, T. D.; Kawano, T.; Kiedrowski, B. C.; Koning, A. J.; Kopecky, S.; Leal, L.; Lestone, J. P.; Lubitz, C.; Márquez Damián, J. I.; Mattoon, C. M.; McCutchan, E. A.; Mughabghab, S.; Navratil, P.; Neudecker, D.; Nobre, G. P. A.; Noguere, G.; Paris, M.; Pigni, M. T.; Plompen, A. J.; Pritychenko, B.; Pronyaev, V. G.; Roubtsov, D.; Rochman, D.; Romano, P.; Schillebeeckx, P.; Simakov, S.; Sin, M.; Sirakov, I.; Sleaford, B.; Sobes, V.; Soukhovitskii, E. S.; Stetcu, I.; Talou, P.; Thompson, I.; van der Marck, S.; Welser-Sherrill, L.; Wiarda, D.; White, M.; Wormald, J. L.; Wright, R. Q.; Zerkle, M.; Žerovnik, G.; Zhu, Y.

2018-02-01

We describe the new ENDF/B-VIII.0 evaluated nuclear reaction data library. ENDF/B-VIII.0 fully incorporates the new IAEA standards, includes improved thermal neutron scattering data and uses new evaluated data from the CIELO project for neutron reactions on 1H, 16O, 56Fe, 235U, 238U and 239Pu described in companion papers in the present issue of Nuclear Data Sheets. The evaluations benefit from recent experimental data obtained in the U.S. and Europe, and improvements in theory and simulation. Notable advances include updated evaluated data for light nuclei, structural materials, actinides, fission energy release, prompt fission neutron and γ-ray spectra, thermal neutron scattering data, and charged-particle reactions. Integral validation testing is shown for a wide range of criticality, reaction rate, and neutron transmission benchmarks. In general, integral validation performance of the library is improved relative to the previous ENDF/B-VII.1 library.

Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

Directory of Open Access Journals (Sweden)

I. S. Коlova

2017-01-01

Full Text Available Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists. The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness. 

[The Relationship Between Quality of Life and Psychological and Behavioral Factors in Patients With Heart Failure Following Cardiac Resynchronization Therapy].

Science.gov (United States)

Huang, Jing; Fang, Jin-Bo; Zhao, Yi-Heng

2018-06-01

While cardiac resynchronization therapy improves the quality of life of patients with heart failure, some psychological and behavioral factors still affect the quality of life of these patients. However, information on the factors that affect the quality of life of these patients is limited. To describe the quality of life and investigate the relationship between quality of life and behavioral and psychological factors such as depression, smoking, drinking, water and sodium restrictions, exercise, and adherence in patients with chronic heart failure following cardiac resynchronization therapy. This cross-sectional study was conducted using the Morisky Medication Adherence Scale, Minnesota Living With Heart Failure Questionnaire, and Cardiac Depression Scale. A convenience sample of 141 patients with heart failure following cardiac resynchronization therapy were recruited from a tertiary academic hospital in Chengdu. The mean overall score of the Minnesota Living With Heart Failure Questionnaire was 30.89 (out of a total possible score of 105). Water restrictions, sodium restrictions, depression, and exercise were all shown to significantly predict quality of life among the participants. This paper describes the quality of life and defines the behavioral factors that affect the quality of life of patients with heart failure following cardiac resynchronization therapy. The findings suggest that nurses should manage and conduct health education for patients in order to improve their quality of life.

CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.

Directory of Open Access Journals (Sweden)

Alessandra Citro

Full Text Available CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control. The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.

Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer

International Nuclear Information System (INIS)

Atsumi, Kazushige; Shioyama, Yoshiyuki; Nakamura, Katsumasa

2010-01-01

The purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stage II-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3, 50-75%; 4, 75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n=14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p=0.0006, p=0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful. (author)

Associations between alcohol use, other psychosocial factors, structural factors and antiretroviral therapy (ART) adherence among South African ART recipients.

Science.gov (United States)

Morojele, Neo K; Kekwaletswe, Connie T; Nkosi, Sebenzile

2014-03-01

We examined whether alcohol use is associated with antiretroviral therapy (ART) adherence independently of structural and psychosocial factors among 304 male and female ART recipients in ART sites in Tshwane, South Africa. ART adherence was assessed by the CASE Adherence Index. Independent variables were demographic, structural, psycho-social, and alcohol use (AUDIT score) factors. In hierarchical multiple regression, demographic variables (Step 1) explained 4 % of variance in ART adherence (p ≤ 0.01). Variance explained increased to 16 % (p ≤ 0.001) after entering structural variables (Step 2); 19 % (p ≤ 0.001) after entering psychosocial variables (Step 3); and 24 % (p ≤ 0.001) after entering AUDIT score (Step 4). Alcohol use is independently associated with ART adherence.

Adherence and competence in two manual-guided therapies for co-occurring substance use and posttraumatic stress disorders: clinician factors and patient outcomes.

Science.gov (United States)

Meier, Andrea; McGovern, Mark P; Lambert-Harris, Chantal; McLeman, Bethany; Franklin, Anna; Saunders, Elizabeth C; Xie, Haiyi

2015-01-01

The challenges of implementing and sustaining evidence-based therapies into routine practice have been well-documented. This study examines the relationship among clinician factors, quality of therapy delivery, and patient outcomes. Within a randomized controlled trial, 121 patients with current co-occurring substance use and posttraumatic stress disorders were allocated to receive either manualized Integrated Cognitive Behavioral Therapy (ICBT) or Individual Addiction Counseling (IAC). Twenty-two clinicians from seven addiction treatment programs were trained and supervised to deliver both therapies. Clinician characteristics were assessed at baseline; clinician adherence and competence were assessed over the course of delivering both therapies; and patient outcomes were measured at baseline and 6-month follow-up. Although ICBT was delivered at acceptable levels, clinicians were significantly more adherent to IAC (p drug problem severity. The differential impact of adherence and competence for both therapy types is consistent with their purported primary target: ICBT for PTSD and IAC for substance use. These findings also suggest the benefits of considering clinician factors when implementing manual-guided therapies. Future research should focus on diverse clinician samples, randomization of clinicians to therapy type, and prospective designs to evaluate models of supervision and quality monitoring.

Transfusion medicine

International Nuclear Information System (INIS)

Murawski, K.; Peetoom, F.

1986-01-01

These proceedings contain 24 selections, including papers presented at the conference of American Red Cross held in May 1985, on the Subject of transfusion medicine. Some of the titles are: Fluosol/sup R/-DA in Radiation Therapy; Expression of Cloned Human Factor VIII and the Molecular Basis of Gene Defects that Cause Hemophilia; DNA-Probing Assay in the Detection of Hepatitis B Virus Genome in Human Peripheral Blood Cells; and Monoclonal Antibodies: Convergence of Technology and Application

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

Science.gov (United States)

Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

2017-01-01

Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

Science.gov (United States)

Wen, W; Frampton, R; Wright, K; Fattore, S; Shadbolt, B; Perampalam, S

2016-02-01

To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Predictors of trimodality therapy and trends in therapy for malignant pleural mesothelioma.

Science.gov (United States)

Nelson, David B; Rice, David C; Niu, Jiangong; Atay, Scott M; Vaporciyan, Ara A; Antonoff, Mara B; Hofstetter, Wayne L; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Tsao, Anne S; Gomez, Daniel R; Giordano, Sharon H; Mehran, Reza J; Sepesi, Boris

2018-05-01

Malignant pleural mesothelioma is an aggressive and rare malignancy that frequently recurs despite aggressive therapy. We evaluated the frequency of treatment with surgery, radiation or chemotherapy, changes in therapy and survival over time and factors associated with the receipt of trimodality therapy. The National Cancer Database (NCDB) was used to query patients with histologically proven malignant pleural mesothelioma (2004-14). Treatment over time was evaluated using the Armitage trend test. Factors associated with the receipt of trimodality therapy were analysed using logistic regression. Among 20 561 patients, only 4028 (20%) underwent cancer-directed surgery; 533 (2.6%) of whom received trimodality therapy. From 2004 to 2014, the use of surgery with chemotherapy increased 87% (P 26 miles for treatment were more likely to undergo trimodality therapy. Additional factors associated with the receipt of trimodality therapy include age less than 70, Charlson comorbidity score of 0 and presence of private insurance. Many malignant pleural mesothelioma patients are not treated with trimodality therapy, with significant variation in treatment patterns. Referrals to high-volume and specialized centres may help offer more therapeutic options and trial or registry enrolment.

Usefulness of radiation treatment planning allpied respiration factor for streotatic body radiation therapy in the lung cancer

Energy Technology Data Exchange (ETDEWEB)

Shin, Sung Pil; Kim, Tae Hyung; So, Woon Young; Back, Geum Mun [Dept. of Medical Health Science, Graduate School, Kangwon National University, Chuncheon (Korea, Republic of)

2016-12-15

We are evaluated the usefulness of radiation treatment planning applied respiration factor for stereotactic body radiation therapy in the lung cancer. Four dimensional computed tomography images were obtained in 10 patients with lung cancer. The radiation treatment plans were established total lung volume according to respiration images (new method) and conventional method. We was analyzed in the lung volume, radiation absorbed dose of lung and main organs (ribs, tracheobronchus, esophagus, spinal cord) around the tumor, respectively. We were confirmed that lung volume and radiation absorbed dose of lung and main organs around the tumor deference according to applied respiration. In conclusion, radiation treatment planning applied respiration factor seems to be useful for stereotactic body radiation therapy in the lung cancer.

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.

Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy.

Science.gov (United States)

Sugimoto, Mitsushige; Yamaoka, Yoshio

2009-01-01

The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable > or =95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA.

COLONIZAÇÃO OU DIÁSPORAS? RESENHA C.-G. SCHWENTZEL (org., M. DANA, St.LEBRETON, Fr.PRÊTEUX, Les diásporas grecques VIII-III s. Paris, Atlande, 2012, 446 páginas, 25 euros. (Dossiê: O Mundo Antigo: Literatura e Historiografia

Directory of Open Access Journals (Sweden)

José Antonio Dabdab Trabulsi

2015-09-01

Full Text Available C.-G. SCHWENTZEL (org., M. DANA, St.LEBRETON, Fr.PRÊTEUX, Les diásporas grecques VIII-III s. Paris, Atlande, 2012, 446 páginas, 25 euros.C.-G. SCHWENTZEL (org., M. DANA, St.LEBRETON, Fr.PRÊTEUX, Les diásporas grecques VIII-III s. Paris, Atlande, 2012, 446 páginas, 25 euros. Recebido em: 02/04/2015  – Aceito em 13/05/2015

Wilms tumour: prognostic factors, staging, therapy and late effects

International Nuclear Information System (INIS)

Kaste, Sue C.; Dome, Jeffrey S.; Babyn, Paul S.; Graf, Norbert M.; Grundy, Paul; Godzinski, Jan; Levitt, Gill A.; Jenkinson, Helen

2008-01-01

Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial development

Wilms tumour: prognostic factors, staging, therapy and late effects

Energy Technology Data Exchange (ETDEWEB)

Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Dome, Jeffrey S. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Babyn, Paul S. [Hospital for Sick Children, Department of Radiology, Toronto (Canada); Graf, Norbert M. [University Hospital of the Saarland, Clinic for Pediatric Oncology and Hematology, Homburg (Germany); Grundy, Paul [University of Alberta, Division of Pediatric Hematology, Oncology and Palliative Care, and Northern Alberta Children' s Cancer Program, Edmonton (Canada); Godzinski, Jan [Mother and Child Institute, Department of Oncological Surgery for Children and Adolescents, Warsaw (Poland); Levitt, Gill A. [Great Ormond Street Hospital for Sick Children NHS Trust, Paediatric Oncology, London (United Kingdom); Jenkinson, Helen [Birmingham Children' s Hospital NHS Trust, Oncology Department, Birmingham (United Kingdom)

2008-01-15

Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial

Analysis of the 4d7 (4f + 6p) and 4p54d9 configurations of Sn VII, Sb VIII and Te IX

International Nuclear Information System (INIS)

Azarov, V.I.; Joshi, Y.N.; Churilov, S.S.; Ryabtsev, A.N.

1994-01-01

The spectra of tin, antimony and tellerium were photographed in the 120-200 A region on 10.7 m and 3 m grazing incidence spectrographs using a triggered spark source. The 4d 8 -4d 7 (4f + 6p) + 4p 5 4d 9 transitions of Sn VII, Sb VIII and Te IX were investigated. In the Sn VII spectrum 109 new lines were classified in the 152-192 A region and 34 new levels were established, in the Sb VIII spectrum 78 new lines were classified in the 138-158 A region and 21 new levels were established, and in the Te IX 76 new lines were classified in the 121-139 A region and 21 new levels were established. Strong configuration interaction among the 4d 7 (np + mf), and 4p 5 4d 9 (n = 5, 6; m = 4, 5) configurations was observed. Least-squares-fitting (LSF) parametric calculations involving configuration interaction were carried out to interpret the observed spectra. (orig.)

Voices of Family Therapy Doctoral Students of Color: Aspirations and Factors Influencing Careers in Academia

Science.gov (United States)

Miller, John K.; Stone, Dana J.

2011-01-01

The authors examined factors influencing career aspirations of doctoral students of color in family therapy doctoral programs across the country, with a special focus on careers in the professoriate. Qualitative interviews were conducted with students at varying levels of degree completion. Respondents discussed barriers to careers in academia as…

Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

Directory of Open Access Journals (Sweden)

Gustavo Romero‐Velez, MD

2014-04-01

Conclusions: ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero‐Velez G, Lisker‐Cervantes A, Villeda‐Sandoval CI, Sotomayor de Zavaleta M, Olvera‐Posada D, Sierra‐Madero JG, Arreguin‐Camacho LO, and Castillejos‐Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30.

Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

DEFF Research Database (Denmark)

Ramlov, Anne; Pedersen, Erik Morre; Røhl, Lisbeth

2017-01-01

and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition......PURPOSE: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin...

An analysis of the incidence and related factors for radiation dermatitis in breast cancer patients who receive radiation therapy

International Nuclear Information System (INIS)

Lee, Sun Young; Kwon, Hyoung Cheol; Kim, Jung Soo; Lee, Heui Kwan

2010-01-01

We analyzed the incidence and related factors of radiation dermatitis; at first, to recognize whether a decrease in radiation dermatitis is possible or not in breast cancer patients who received radiation therapy. Of 338 patients, 284 with invasive breast cancer who received breast conservation surgery with radiotherapy at Chonbuk National University Hospital from January 2007 to June 2009 were evaluated. Patients who also underwent bolus, previous contralateral breast irradiation and irradiation on both breasts were excluded. For patients who appeared to have greater than moderate radiation dermatitis, the incidence and relating factors for radiation dermatitis were analyzed retrospectively. A total of 207 and 77 patients appeared to have RTOG grade 0/1 or above RTOG grade 2 radiation dermatitis, respectively. The factors found to be statistically significant for the 77 patients who appeared to have greater than moderate radiation dermatitis include the presence of lymphocele due to the stasis of lymph and lymph edema which affect the healing disturbance of radiation dermatitis (p=0.003, p=0.001). Moreover, an allergic reaction to plaster due to the immune cells of skin and the activation of cytokine and concomitant hormonal therapy were also statistically significant factors (p=0.001, p=0.025). Most of the breast cancer patients who received radiation therapy appeared to have a greater than mild case of radiation dermatitis. Lymphocele, lymphedema, an allergy to plaster and concomitant hormonal therapy which affect radiation dermatitis were found to be significant factors. Consequently, we should eliminate lymphocele prior to radiation treatment for patients who appear to have an allergic reaction to plaster. We should also instruct patients of methods to maintain skin moisture if they appear to have a greater than moderate case of radiation dermatitis.

Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya

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Wakibi Samwel N

2011-12-01

Full Text Available Abstract Background Antiretroviral therapy (ART requires high-level (> 95% adherence. Kenya is rolling out ART access programmes and, issue of adherence to therapy is therefore imperative. However, published data on adherence to ART in Kenya is limited. This study assessed adherence to ART and identified factors responsible for non adherence in Nairobi. Methods This is a multiple facility-based cross-sectional study, where 416 patients aged over 18 years were systematically selected and interviewed using a structured questionnaire about their experience taking ART. Additional data was extracted from hospital records. Patients were grouped into adherent and non-adherent based on a composite score derived from a three questions adherence tool developed by Center for Adherence Support Evaluation (CASE. Multivariate regression model was used to determine predictors of non-adherence. Results Overall, 403 patients responded; 35% males and 65% females, 18% were non-adherent, and main (38% reason for missing therapy were being busy and forgetting. Accessing ART in a clinic within walking distance from home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019 and difficulty with dosing schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011 predicted non-adherence. Conclusions The study found better adherence to HAART in Nairobi compared to previous studies in Kenya. However, this can be improved further by employing fitting strategies to improve patients' ability to fit therapy in own lifestyle and cue-dose training to impact forgetfulness. Further work to determine why patients accessing therapy from ARV clinics within walking distance from their residence did not adhere is recommended.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

Science.gov (United States)

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

Reliability factors of tube-to-tubesheet joints

International Nuclear Information System (INIS)

Sang, Z.F.; Zhu, Y.Z.; Widera, G.E.O.

1992-01-01

The main purpose of this paper is to provide an applicable method to establish reliability factors for expanded tube-to-tubesheet joints. The paper also reports on the results of a preliminary study to validate experimentally the reliability efficiencies listed in Table A-2 of Appendix A of Section VIII, Division 1, of the ASME Boiler and Pressure Vessel Code. A comparison between the actual reliability factors f r , determined from testing the damage strength of the joint and calculated according to Appendix A-4 of the ASME Code, and those of Table A-2 is carried out. The results are discussed in light of the restrictions inherent in Table A-2. It is confirmed that some existing values of f r are conservative while others are less so. (orig.)

Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC

International Nuclear Information System (INIS)

Langer, Corey J.

2004-01-01

Combination chemotherapy regimens have emerged as the standard approach in advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month increase in median survival after platinum-based therapy vs. best supportive care, and an absolute 10% improvement in the 1-year survival rate. Just as importantly, cytotoxic therapy has produced benefits in symptom control and quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine, and irinotecan, have expanded our therapeutic options in the treatment of advanced non-small-cell lung cancer. Despite their contributions, we have reached a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative group studies and 1-year survival rates stable between 30% and 40%. It is doubtful that substituting one agent for another in various combinations will lead to any further improvement in these rates. The thrust of current research has focused on targeted therapy, and epidermal growth factor receptor inhibition is one of the most promising clinical strategies. Epidermal growth factor receptor inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical models have demonstrated synergy for all these agents in combination with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to lung cancer therapy. However, serious clinical challenges persist. These include the identification of the optimal dose(s); the proper integration of these agents into popular, established cytotoxic regimens; and the selection of the optimal setting(s) in which

Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

International Nuclear Information System (INIS)

Sakai, T.; Kisiel, W.

1990-01-01

Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125 I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

2018-01-01

Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: Family studies indicate a mutation type-dependent sex ratio of mutation frequencies

Energy Technology Data Exchange (ETDEWEB)

Becker, J.; Schmidt, W.; Olek, K. [Univ. of Bonn (Germany)] [and others

1996-04-01

The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients-all exclusively from sporadic families-were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.7%). Fifty-five patients (37.4%) showed a F8A-gene inversion, 47 (32.0%) a point mutation, 14 (9.5%) a small deletion, 8 (5.4%) a large deletion, and 2 (1.4%) a small insertion. Further, four (2.7%) mutations were localized but could not be sequenced yet. No mutation could be identified in 17 patients (11.6%). Sixteen (10.9%) of the P identified mutations occurred in the B domain. Four of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicisms were detected in 3 (3.9%) of 76 patients` mothers, comprising 3 of 16 de novo mutations in the patients` mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 two-generation and 28 of 34 three-generation families. On the basis of these data, the male:female ratio of mutation frequencies (k) was estimated as k = 3.6. By use of the quotients of mutation origin in maternal grandfather to patient`s mother or to maternal grandmother, k was directly estimated as k = 15 and k = 7.5, respectively. Considering each mutation type separately, we revealed a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a >10-fold- higher mutation rate in male germ cells, whereas deletions showed a >5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other diseases like Duchenne muscular dystrophy, our results indicate that at least for X-chromosomal disorders the male:female mutation rate of a disease is determined by its proportion of the different mutation types. 68 refs., 1 fig., 5 tabs.

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

Science.gov (United States)

Sugino, Kiminori; Nagahama, Mitsuji; Kitagawa, Wataru; Ohkuwa, Keiko; Uruno, Takashi; Matsuzu, Kenichi; Suzuki, Akifumi; Masaki, Chie; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Ogimi, Yuna; Ito, Koichi

2018-03-28

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

Directory of Open Access Journals (Sweden)

Tetsuya Ishida

2014-01-01

Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

NARCIS (Netherlands)

Siefried, Krista J; Mao, Limin; Kerr, Stephen; Cysique, Lucette A; Gates, Thomas M; McAllister, John; Maynard, Anthony; de Wit, John; Carr, Andrew

2017-01-01

BACKGROUND: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS: Adults on

Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

NARCIS (Netherlands)

Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K.; van Wijk, Albert C.; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C.; van Gulik, Thomas M.; Storm, Gert; Heger, Michal

2016-01-01

Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of

Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

NARCIS (Netherlands)

Weijer, R.; Broekgaarden, M.; Krekorian, M.; Alles, L.K.; van Wijk, A.C; Mackaaij, C.; Verheij, J.; van der Wal, A.C.; van Gullik, T.M.; Storm, Gerrit; Heger, M.

2016-01-01

Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

Science.gov (United States)

Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

2017-03-21

To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy.

Science.gov (United States)

Van der Meer, Marrit; Hoving, Jan L; Vermeulen, Marjolein I M; Herenius, Marieke M J; Tak, Paul P; Sluiter, Judith K; Frings-Dresen, Monique H W

2011-01-01

To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with respect to work participation. Experiences regarding work participation varied and ranged from fatigue at work, having no job control, not being understood by the work environment or difficulty dealing with emotions as a result of interaction within the work environment. Support by health care professionals for work participation was considered important, especially concerning social or psychological issues. Advice in becoming aware of one's changes in abilities was highly appreciated, as was the availability of professional advice in times of an urgent work issue due to RA. Employees mentioned an increase in social support at work and job control as important facilitating factors for work participation. Although patients with RA report improvement in their work functioning after starting anti-TNF therapy, employees continue facing challenges in working life due to RA. For support concerning work participation, it is recommended that health care professionals are more aware of work-related problems in patients with RA treated with anti-TNF therapy.

Monte Carlo computed machine-specific correction factors for reference dosimetry of TomoTherapy static beam for several ion chambers

International Nuclear Information System (INIS)

Sterpin, E.; Mackie, T. R.; Vynckier, S.

2012-01-01

Purpose: To determine k Q msr ,Q o f msr ,f o correction factors for machine-specific reference (msr) conditions by Monte Carlo (MC) simulations for reference dosimetry of TomoTherapy static beams for ion chambers Exradin A1SL, A12; PTW 30006, 31010 Semiflex, 31014 PinPoint, 31018 microLion; NE 2571. Methods: For the calibration of TomoTherapy units, reference conditions specified in current codes of practice like IAEA/TRS-398 and AAPM/TG-51 cannot be realized. To cope with this issue, Alfonso et al. [Med. Phys. 35, 5179–5186 (2008)] described a new formalism introducing msr factors k Q msr ,Q o f msr ,f o for reference dosimetry, applicable to static TomoTherapy beams. In this study, those factors were computed directly using MC simulations for Q 0 corresponding to a simplified 60 Co beam in TRS-398 reference conditions (at 10 cm depth). The msr conditions were a 10 × 5 cm 2 TomoTherapy beam, source-surface distance of 85 cm and 10 cm depth. The chambers were modeled according to technical drawings using the egs++ package and the MC simulations were run with the egs c hamber user code. Phase-space files used as the source input were produced using PENELOPE after simulation of a simplified 60 Co beam and the TomoTherapy treatment head modeled according to technical drawings. Correlated sampling, intermediate phase-space storage, and photon cross-section enhancement variance reduction techniques were used. The simulations were stopped when the combined standard uncertainty was below 0.2%. Results: Computed k Q msr ,Q o f msr ,f o values were all close to one, in a range from 0.991 for the PinPoint chamber to 1.000 for the Exradin A12 with a statistical uncertainty below 0.2%. Considering a beam quality Q defined as the TPR 20,10 for a 6 MV Elekta photon beam (0.661), the additional correction k Q msr, Q f msr, f ref to k Q,Q o defined in Alfonso et al. [Med. Phys. 35, 5179–5186 (2008)] formalism was in a range from 0.997 to 1.004.Conclusion: The MC computed

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder