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Sample records for severe acquired adamts13

  1. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    Science.gov (United States)

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  2. Thrombotic thrombocytopenic purpura with decreased level of ADAMTS-13 activity and increased level of ADAMTS-13 inhibitor in an adolescent

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    Eun Mi Yang

    2010-03-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

  3. ADAMTS-13 level in children with severe diarrhea-associated hemolytic uremic syndrome: Unmasking new association

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    Naglaa A Khalifa

    2018-01-01

    Full Text Available Severe deficiency of ADAMTS-13 leads to thrombotic thrombocytopenic purpura. Few studies have reported reduced activity of ADAMTS-13 in patients with atypical and typical hemolytic uremic syndrome (HUS. We hypothesized that ADAMTS-13 deficiency might play a role in the pathogenesis of severe HUS. This study aimed to evaluate the ADAMTS-13 level in severe typical HUS. This prospective case–control study was carried out in the Pediatric Nephrology Unit and Clinical Pathology Department, Faculty of Medicine, Zagazig University from February 2013 to February 2014. The study included 15 consecutive children with typical HUS as well as 15 healthy children as a control group. Routine laboratory investigations were performed. Assessment of serum ADAMTS-13 level was performed using the Quantikine human ADAMTS-13 ELISA kit. Data were analyzed using Statistical Package for Social Sciences version 16. Nonparametric values were expressed as median and range, and the median of two groups was tested by Mann–Whitney test. The serum ADAMTS-13 level was significantly lower in HUS patients when compared to the control group (P < 0.05. There were significant negative correlations between ADAMTS-13 level and duration on dialysis, as well as serum urea and creatinine. Furthermore, there were significant positive correlations between serum ADAMTS-13 level and both hemoglobin level and platelet count. Our study suggests that the ADAMTS-13 level was decreased in children with severe typical HUS and its deficiency correlated with disease severity.

  4. Prasugrel and Acquired Thrombotic Thrombocytopenic Purpura Associated with ADAMTS13 Activity Deficiency

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    Yanet Parodis Lopez

    2016-07-01

    Full Text Available We report a case of a 64-year-old male who, 44 days after starting treatment with prasugrel, presented with severe thrombocytopenia, anemia, renal failure, and severe ADAMTS13 activity deficiency, along with a high titer of autoantibodies to this protease.

  5. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura

    KAUST Repository

    Lancellotti, S.

    2015-08-13

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  6. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura

    KAUST Repository

    Lancellotti, S.; Peyvandi, F.; Pagliari, M.; Cairo, A.; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, I.; Mastrangelo, S.; Cavallo, Luigi; Oliva, R.; De Cristofaro, R.

    2015-01-01

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3 %) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme’s activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285–304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  7. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  8. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy.

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    Mariotte, Eric; Azoulay, Elie; Galicier, Lionel; Rondeau, Eric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; de Maistre, Emmanuel; Provôt, François; Delmas, Yahsou; Perez, Pierre; Benhamou, Ygal; Stepanian, Alain; Coppo, Paul; Veyradier, Agnès

    2016-05-01

    Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 [91%] cases), whereas non-idiopathic diseases were

  9. Probing ADAMTS13 substrate specificity using phage display.

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    Karl C Desch

    Full Text Available Von Willebrand factor (VWF is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2' and P11', for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13-VWF exosite interactions outside of VWF73.

  10. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

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    Bendapudi, Pavan K; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S

    2015-12-01

    The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P 10% varied significantly across the institutions in our consortium (13·2-63·8%, P 10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE. © 2015 John Wiley & Sons Ltd.

  11. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

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    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  12. Probing ADAMTS13 Substrate Specificity using Phage Display

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    Desch, Karl C.; Kretz, Colin; Yee, Andrew; Gildersleeve, Robert; Metzger, Kristin; Agrawal, Nidhi; Cheng, Jane; Ginsburg, David

    2015-01-01

    Von Willebrand factor (VWF) is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2’ and P11’, for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13–VWF exosite interactions outside of VWF73. PMID:25849793

  13. Plasma ADAMTS-13 protein is not associated with portal hypertension or hemodynamic changes in patients with cirrhosis

    DEFF Research Database (Denmark)

    Wiese, Signe; Timm, Annette; Nielsen, Lars B

    2016-01-01

    BACKGROUND: Activated hepatic stellate cells synthesize the matrix metalloprotease ADAMTS13, which may be involved in the development of liver cirrhosis and portal hypertension. Plasma ADAMTS13 activity has been reported as both increased and decreased in cirrhosis, but ADAMTS13 protein has...... in cirrhosis. However, ADAMTS13 was unrelated to portal hypertension and systemic hemodynamics. In conclusion, ADAMTS13 does not appear to be associated to disease severity or the hemodynamic derangement in patients with cirrhosis....... not previously been examined. AIM: To evaluate ADAMTS13 protein in the hepatic circulation and the relation to disease severity, portal pressure, and systemic hemodynamics in cirrhotic patients. METHODS: Sixty-one cirrhotic patients (Child class: A=22; B=21; C=18) and nine healthy controls underwent a liver vein...

  14. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    Science.gov (United States)

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. ADAMTS13 Gene Mutations in Children with Hemolytic Uremic Syndrome

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    Choi, Hyoung Soo; Cheong, Hae Il; Kim, Nam Keun

    2011-01-01

    We investigated ADAMTS13 activity as well as the ADAMTS13 gene mutation in children with hemolytic uremic syndrome (HUS). Eighteen patients, including 6 diarrhea-negative (D-HUS) and 12 diarrhea-associated HUS (D+HUS) patients, were evaluated. The extent of von Willebrand factor (VWF) degradation was assayed by multimer analysis, and all exons of the ADAMTS13 gene were PCR-amplified using Taq DNA polymerase. The median and range for plasma activity of ADAMTS13 in 6 D-HUS and 12 D+HUS patients were 71.8% (22.8-94.1%) and 84.9% (37.9-119.9%), respectively, which were not statistically significantly different from the control group (86.4%, 34.2-112.3%) (p>0.05). Five ADAMTS13 gene mutations, including 2 novel mutations [1584+2T>A, 3941C>T (S1314L)] and 3 polymorphisms (Q448E, P475S, S903L), were found in 2 D-HUS and one D+HUS patients, which were not associated with deficiency of ADAMTS13 activity. Whether these mutations without reduced ADAMTS13 activity are innocent bystanders or predisposing factors in HUS remains unanswered. PMID:21488199

  16. Increased expressions of ADAMTS-13, neuronal nitric oxide synthase, and neurofilament correlate with severity of neuropathology in Border disease virus-infected small ruminants.

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    Gungor Cagdas Dincel

    Full Text Available Border Disease (BD, caused by Pestivirus from the family Flaviviridae, leads to serious reproductive losses and brain anomalies such as hydranencephaly and cerebellar hypoplasia in aborted fetuses and neonatal lambs. In this report it is aimed to investigate the expression of neuronal nitric oxide synthase (nNOS, A Disintegrin And Metalloprotease with Thrombospondin type I repeats-13 (ADAMTS-13, and neurofilament (NF in the brain tissue in small ruminants infected with Border Disease Virus (BDV and to identify any correlation between hypomyelinogenesis and BD neuropathology. Results of the study revealed that the levels of ADAMTS-13 (p<0.05, nNOS (p<0.05, and NF (p<0.05 were remarkably higher in BDV-infected brain tissue than in the uninfected control. It was suggested that L-arginine-NO synthase pathway is activated after infection by BDV and that the expression of NF and nNOS is associated with the severity of BD. A few studies have focused on ADAMTS-13 expression in the central nervous system, and its function continues to remain unclear. The most prominent finding from our study was that ADAMTS-13, which contain two CUB domains, has two CUB domains and its high expression levels are probably associated with the development of the central nervous system (CNS. The results also clearly indicate that the interaction of ADAMTS-13 and NO may play an important role in the regulation and protection of the CNS microenvironment in neurodegenerative diseases. In addition, NF expression might indicate the progress of the disease. To the best of the authors'knowledge, this is the first report on ADAMTS-13 expression in the CNS of BDV-infected small ruminants.

  17. ADAMTS13 expression in human chondrosarcoma cells induced by insulin

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    Rıdvan Fırat

    2014-06-01

    Full Text Available Objectives: A Disintegrin-like Metalloproteinase with Thrombospondin Motifs (ADAMTS proteins is a proteinase enzyme group that primarily located in the extracellular matrix (ECM. Insulin has been known to stimulate proteoglycan biosynthesis in chondrosarcoma chondrocytes and thereby the levels of ADAMTS proteins. The aim of this study is to evaluate the time-dependent effects of insulin on the ADAMTS13 expression in OUMS-27 human chondrosarcoma cell line to test the hypothesis that insulin diminishes ADAMTS13 expression because of its anabolic effects. Methods: To test this hypothesis OUMS-27 cells were cultured in Dulbecco’s modified Eagle’ medium (DMEM containing 10μg/mL insulin. The medium containing insulin was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and protein and RNA isolations were performed at the proper times. The levels of RNA expression of ADAMTS13 was quantified by qRT-PCR using appropriate primers while protein levels was detected by Western blot technique using anti-ADAMTS13 antibody. Results: Although there was a decrease in both RNA and protein levels in insulin-applied groups compared to the control cells, it was not statistically significant. Conclusion: Under the light of our findings, it is suggested that insulin does not participate in regulation of ADAMTS13 in OUMS-27 chondrosarcoma cells. J Clin Exp Invest 2014; 5 (2: 226-232

  18. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  19. Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

    Science.gov (United States)

    Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

    2015-10-22

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. High throughput protease profiling comprehensively defines active site specificity for thrombin and ADAMTS13.

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    Kretz, Colin A; Tomberg, Kärt; Van Esbroeck, Alexander; Yee, Andrew; Ginsburg, David

    2018-02-12

    We have combined random 6 amino acid substrate phage display with high throughput sequencing to comprehensively define the active site specificity of the serine protease thrombin and the metalloprotease ADAMTS13. The substrate motif for thrombin was determined by >6,700 cleaved peptides, and was highly concordant with previous studies. In contrast, ADAMTS13 cleaved only 96 peptides (out of >10 7 sequences), with no apparent consensus motif. However, when the hexapeptide library was substituted into the P3-P3' interval of VWF73, an exosite-engaging substrate of ADAMTS13, 1670 unique peptides were cleaved. ADAMTS13 exhibited a general preference for aliphatic amino acids throughout the P3-P3' interval, except at P2 where Arg was tolerated. The cleaved peptides assembled into a motif dominated by P3 Leu, and bulky aliphatic residues at P1 and P1'. Overall, the P3-P2' amino acid sequence of von Willebrand Factor appears optimally evolved for ADAMTS13 recognition. These data confirm the critical role of exosite engagement for substrates to gain access to the active site of ADAMTS13, and define the substrate recognition motif for ADAMTS13. Combining substrate phage display with high throughput sequencing is a powerful approach for comprehensively defining the active site specificity of proteases.

  1. Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease

    Science.gov (United States)

    Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long

    2015-01-01

    Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102

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

    Science.gov (United States)

    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.

  3. [Variety of thrombotic thrombocytopenic purpura clinical course in Polish family members with ADAMTS 13 gene mutation].

    Science.gov (United States)

    Hyla-Klekot, Lidia; Kucharska, Grazyna; Słonka, Karina

    2013-03-01

    The congenital form of thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrom) is a result of genetically conditioned dysfunction of protease ADAMTS 13 enzyme which is responsible for von Wiellebrand factor multimer disintegration. The disease is inherited autosomally and recessively. The decrease of ADAMTS 13 activity results in intravascular clotting process activation with rapid lowering of platelet count, haemolytic anaemia, and occurence of schistocytes. Clinically, the disease is characterized by a range of symptoms such as severe jaundice in neonatal period, embolicthrombotic incidents of nervous system and progressive dysfunction of kidneys and other organs. Delaying diagnosis and hence administering of freshly frozen plasma leads to death. Molecular diagnosis allows for identification of genetical profile of the patient, and showing lowered enzyme activity is a basis for regular prophylactic plasma administration which is the protease donor. In our study we present members of a Polish family identified with ADAMTS 13 mutation. 52 old male with heterozygotic mutation of exon 29 (4143_4144insA) and in exon 19 (c2281G>A; Gly761Ser), experienced a few episodes of ischaemic stroke with ongoing neurological deficiency and developed chronic kidney disease. His 16-year old daughter with double homozygotic mutation in exon 29 (4143_4144insA) after severe episode of TTP at the age of 4 has been receiving plasma every 2 weeks for 12 years, which prevented her from other disorders. Target treatment introduced to clinical practice by means of ADAMTS 13 obtained by genetic recombination technology raises hopes.

  4. Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

    2012-01-01

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

  5. Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat).

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L; Blaisdell, Adam; Hunt, Ryan C; Newell, Jordan; Tseng, Sandra C; Hershko, Alon Y; Choi, Jae Won; Sauna, Zuben E; Wu, Andrew; Bram, Richard J; Komar, Anton A; Kimchi-Sarfaty, Chava

    2012-12-28

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients.

  6. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Directory of Open Access Journals (Sweden)

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  7. Platelet-free shear flow assay facilitates analysis of shear-dependent functions of VWF and ADAMTS13.

    Science.gov (United States)

    Kraus, Emma; Kraus, Kristina; Obser, Tobias; Oyen, Florian; Klemm, Ulrike; Schneppenheim, Reinhard; Brehm, Maria A

    2014-12-01

    The multimeric form of von Willebrand factor (VWF), is the largest soluble protein in mammals and exhibits a multidomain structure resulting in multiple functions. Upon agonist stimulation endothelial cells secrete VWF multimers from Weibel-Palade bodies into the blood stream where VWF plays an essential role in platelet-dependent primary hemostasis. Elongation of VWF strings on the cells' surface leads to accessibility of VWF binding sites for proteins, such as platelet membrane glycoprotein Ib. The prothrombotic strings are size-regulated by the metalloprotease ADAMTS13 by shear force-activated proteolytic cleavage. VWF string formation was induced by histamine stimulation of HUVEC cells under unidirectional shear flow and VWF strings were detected employing the VWF binding peptide of platelet glycoprotein Ib coupled to latex beads. VWF strings were then used as substrate for kinetic studies of recombinant and plasma ADAMTS13. To investigate specific aspects of the shear-dependent functions of VWF and ADAMTS13, we developed a shear flow assay that allows observation of VWF string formation and their degradation by ADAMTS13 without the need for isolated platelets. Our assay specifically detects VWF strings, can be coupled with fluorescent applications and allows semi-automated, quantitative assessment of recombinant and plasma ADAMTS13 activity. Our assay may serve as a valuable research tool to investigate the biochemical characteristics of VWF and ADAMTS13 under shear flow and could complement diagnostics of von Willebrand Disease and Thrombotic Thrombocytopenic Purpura as it allows detection of shear flow-dependent dysfunction of VWD-associated VWF mutants as well as TTP-associated ADAMTS13 mutants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. ADAMTS-1 in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Emina Vorkapic

    Full Text Available Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA. Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS. Pathogenesis of these proteases in AAA has not been investigated until date.Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter.Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don't seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

  9. Predictive value of ADAMTS-13 on concealed chronic renal failure in COPD patients

    Science.gov (United States)

    Zeng, Mian; Chen, Qingui; Liang, Wenjie; He, Wanmei; Zheng, Haichong; Huang, Chunrong

    2017-01-01

    Background Impaired renal function is often neglected in COPD patients. Considering that COPD patients usually have an ongoing prothrombotic state and systemic inflammation status, we investigated the association among them and explored the predictive value of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), on concealed chronic renal failure (CRF) in COPD patients. Methods COPD patients were recruited from the First Affiliated Hospital of Sun Yat-Sen University between January 2015 and December 2016. Control was selected from contemporaneous hospitalized patients without COPD and matched by age and gender at a ratio of 1:1. Estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula, and all subjects were categorized as having normal renal function (eGFR ≥60 mL min−1 1.73 m−2) and having concealed CRF (normal serum creatinine while eGFR <60 mL min−1 1.73 m−2). Independent correlates of concealed CRF were investigated by logistic regression analysis, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ADAMTS-13. Results In total, 106 COPD and 106 non-COPD patients were finally recruited, and the incidences of concealed CRF were 19.81% and 7.55%, respectively. ADAMTS-13 (odds ratio [OR] =0.858, 95% CI =0.795–0.926), D-dimer (OR =1.095, 95% CI =1.027–1.169), and C-reactive protein (OR =1.252, 95% CI =1.058–1.480) were significantly associated with concealed CRF. Sensitivity and specificity at an ADAMTS-13 cutoff of 318.72 ng/mL were 100% and 81.2%, respectively. The area under the ROC curve was 0.959. Conclusion Prothrombotic state and systemic inflammation status might contribute to explaining the high incidence of concealed CRF in COPD, and plasma ADAMTS-13 levels may serve as a strong predictor. PMID:29255356

  10. A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

    Directory of Open Access Journals (Sweden)

    Risa Yamada

    2011-01-01

    Full Text Available Thrombotic thrombocytopenia purpura (TTP caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA. Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE. In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

  11. 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.

  12. Characterization of coding synonymous and non-synonymous variants in ADAMTS13 using ex vivo and in silico approaches.

    Directory of Open Access Journals (Sweden)

    Nathan C Edwards

    Full Text Available Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s. However, mounting evidence shows that these "silent" variations can have a significant impact on protein expression and function and should no longer be considered "silent". Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein.

  13. Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

    Science.gov (United States)

    Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

    2018-02-01

     Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.

  14. Pregnancy shortly after an acute episode of severe acquired thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Panaitescu, Anca M; Stoia, Razvan; Ciobanu, Anca M; Demetrian, Mihaela; Peltecu, Gheorghe

    2016-12-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal condition. In women with a previous history of TTP there is increased risk of recurrence during pregnancy and the puerperium. There is some evidence that the risk of relapse during pregnancy is increased if the interval between the event and conception is short. We present a case in which pregnancy was achieved a few days after full recovery from an acute episode of severe acquired TTP (ADAMTS13 activity <0.1%) which was successfully treated with four courses of plasma exchange. There was no relapse of TTP during pregnancy and a healthy baby was delivered at term; the puerperium was uneventful. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    Science.gov (United States)

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

    2016-07-01

    Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even

  17. [Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm].

    Science.gov (United States)

    Naito, Chiaki; Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Mihara, Masahiro; Handa, Hiroshi; Isonishi, Ayami; Hayakawa, Masaki; Matsumoto, Masanori; Nojima, Yoshihisa

    2016-03-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors.

  18. Activation of pathways involved in HUVEC apoptosis and proliferation. Sex hormones agonist related. Effect of hormones on von Willebrand factor and ADAMTS 13 release

    OpenAIRE

    Powazniak, Yanina

    2008-01-01

    El VWF es una glicoproteína adhesiva, sintetizada en las CE y megacariocitos. Se sintetiza en forma monomérica, luego se organiza en dímeros y se multimeriza. El VWF media la adhesión de plaquetas al subendotelio vascular dañado y lel transporte del factor FVIII. La ADAMTS13, proteasa que cliva al VWF, pertenece a la familia de metaloproteasas ADAMTS, llamadas así por la combinación característica de una desintegrina y una metaloproteasa con motivos trombospondina tipo 1. La ADAMTS13 es sinte...

  19. Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene

    DEFF Research Database (Denmark)

    Rank, Cecilie Utke; Kremer Hovinga, Johanna; Taleghani, Magnus Mansouri

    2014-01-01

    , causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26-year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity...

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

    Science.gov (United States)

    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.

  1. Acquired Thrombotic Thrombocytopenic Purpura in a Patient with Pernicious Anemia

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    Ramesh Kumar Pandey

    2017-01-01

    Full Text Available Introduction. Acquired thrombotic thrombocytopenic purpura (TTP has been associated with different autoimmune disorders. However, its association with pernicious anemia is rarely reported. Case Report. A 46-year-old male presented with blood in sputum and urine for one day. The vitals were stable. The physical examination was significant for icterus. Lab tests’ results revealed leukocytosis, macrocytic anemia, severe thrombocytopenia, renal dysfunction, and unconjugated hyperbilirubinemia. He had an elevated LDH, low haptoglobin levels with many schistocytes, nucleated RBCs, and reticulocytes on peripheral smear. Low ADAMTS13 activity (<10% with elevated ADAMTS13 antibody clinched the diagnosis of severe acquired TTP, and plasmapheresis was started. There was an initial improvement in his hematological markers, which were however not sustained on discontinuation of plasmapheresis. For his refractory TTP, he was resumed on daily plasmapheresis and Rituximab was started. Furthermore, the initial serum Vitamin B12 and reticulocyte index were low in the presence of anti-intrinsic factor antibody. So with the concomitant diagnosis of pernicious anemia, Vitamin B12 was supplemented. The rest of the immunological workups were negative. Subsequently, his symptoms resolved and his hematological parameters improved. Discussion. While pernicious anemia can masquerade as TTP, an actual association between the two can also occur and needs further evaluation and characterization.

  2. Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization

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    Van Meir Erwin G

    2005-02-01

    Full Text Available Abstract Background The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10, thrombotic thrombocytopenic purpura (ADAMTS13, and Ehlers-Danlos syndrome type VIIC (ADAMTS2 in humans and belted white-spotting mutation in mice (ADAMTS20. Results Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu, chordate (Ciona and invertebrate (Drosophila and Caenorhabditis ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. Conclusions The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15 that may have distinct aggrecanase and angiogenesis functions.

  3. Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT).

    Science.gov (United States)

    Ding, Yun; O'Keefe, Heather; DeLorey, Jennifer L; Israel, David I; Messer, Jeffrey A; Chiu, Cynthia H; Skinner, Steven R; Matico, Rosalie E; Murray-Thompson, Monique F; Li, Fan; Clark, Matthew A; Cuozzo, John W; Arico-Muendel, Christopher; Morgan, Barry A

    2015-08-13

    The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel therapeutic target for osteoarthritis. Here, we use DNA-encoded Library Technology (ELT) to identify novel ADAMTS-4 inhibitors from a DNA-encoded triazine library by affinity selection. Structure-activity relationship studies based on the selection information led to the identification of potent and highly selective inhibitors. For example, 4-(((4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-6-(((4-methylpiperazin-1-yl)methyl)amino)-1,3,5-triazin-2-yl)amino)methyl)-N-ethyl-N-(m-tolyl)benzamide has IC50 of 10 nM against ADAMTS-4, with >1000-fold selectivity over ADAMT-5, MMP-13, TACE, and ADAMTS-13. These inhibitors have no obvious zinc ligand functionality.

  4. Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.

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    Cao, Wenjing; Pham, Huy P; Williams, Lance A; McDaniel, Jenny; Siniard, Rance C; Lorenz, Robin G; Marques, Marisa B; Zheng, X Long

    2016-11-01

    Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (Ppurpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. Copyright© Ferrata Storti Foundation.

  5. ADAMTS14 Gene Polymorphism and Environmental Risk in the Development of Oral Cancer.

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    Shih-Chi Su

    Full Text Available Oral cancer is a common malignancy that is shown to be causally associated with hereditary and acquired factors. ADAMTS14 is a member of the ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin motifs metalloproteinase family that plays an important role in extracellular matrix (ECM assembly and degradation. Elevation or deficiency of certain ADAMTS proteinases has been known to be implicated in a wide range of pathological processes including atherosclerosis, arthritis, and cancer. The present study aimed to explore the impact of ADAMTS14 gene polymorphisms, combined with environmental risks on the susceptibility to oral tumorigenesis.Four single-nucleotide polymorphisms (SNPs of the ADAMTS14 gene, including rs10823607, rs12774070, rs4747096, and rs61573157 were evaluated from 1200 normal controls and 850 patients with oral cancer. We failed to detect a significant association of four individual SNPs with oral cancer between case and control group. However, while considering behavioral exposure of environmental carcinogens, the presence of four ADAMTS14 SNPs, combined with betel nut chewing and/or smoking, profoundly leveraged the risk of oral cancer. Moreover, we observed a significant association of rs12774070, which is predicted to alter the expression and function of ADAMTS14 by in silico and bioinformatics analyses, with poor tumor cell differentiation (AOR: 0.59; 95% CI: 0.38-0.92; p = 0.02 in patients who chewed betel nuts.These results implicate the interaction between ADAMTS14 gene polymorphisms and environmental mutagens as a risk factor of oral tumorigenesis and suggest a correlation of rs12774070 with the degree of oral tumor cell differentiation.

  6. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

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    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  7. von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.

    Science.gov (United States)

    Morici, Nuccia; Cantoni, Silvia; Panzeri, Francesco; Sacco, Alice; Rusconi, Chiara; Stucchi, Miriam; Oliva, Fabrizio; Cattaneo, Marco

    2017-07-01

    Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS. Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y 12 were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y 12 antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS. The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The impact of parathyroidectomy on serum ADAMTS1, ADAMTS4 levels, insulin resistance, and subclinical cardiovascular disease in primary hyperparathyroidism.

    Science.gov (United States)

    Karakose, Melia; Caliskan, Mustafa; Arslan, Muyesser Sayki; Demirci, Taner; Karakose, Suleyman; Cakal, Erman

    2017-01-01

    Primary hyperparathyroidism has been associated with increased incidence of morbidity and mortality of the cardiovascular system. The etiopathogenetic mechanisms underlying this association are still not completely clear. Accumulating evidence suggested that a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) has a role in the development of inflammation and atherosclerosis. In this study, we aimed to determine whether there is a change in serum levels of ADAMTS1, ADAMTS4, carotid intima-media thickness, and cardiovascular risk score after the surgery and also whether there is a relationship between ADAMTS levels and cardiovascular risk score in hypercalcemic primary hyperparathyroidism patients. The study included the 48 consecutive newly diagnosed patients with primary hyperparathyroidism. The patients were evaluated before and six months after parathyroidectomy. The Framingham score is used to calculate cardiovascular risk. Serum ADAMTS levels were determined by a human enzyme-linked immunoassay in all subjects. The fasting glucose, fasting insulin levels and HOMA values were decreased significantly in all patients after surgery compared to the pretreatment values (p hyperparathyroidism compared to the preoperative values (p  0.05). There were statistically significant relationship between cardiovascular risk score and waist/hip ratio, calcium, LDL-cholesterol, carotid intima-media thickness, ADAMTS4 values. Based on the results of the present study, fasting glucose, fasting insulin levels, ADAMTS1, ADAMTS4, and carotid intima-media thickness might be an additional parameters during the management of patients with primary hyperparathyroidism, since these factors might improve after surgery.

  9. Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5.

    Science.gov (United States)

    Rogerson, Fraser M; Stanton, Heather; East, Charlotte J; Golub, Suzanne B; Tutolo, Leonie; Farmer, Pamela J; Fosang, Amanda J

    2008-06-01

    To characterize aggrecan catabolism and the overall phenotype in mice deficient in both ADAMTS-4 and ADAMTS-5 (TS-4/TS-5 Delta-cat) activity. Femoral head cartilage from the joints of TS-4/TS-5 Delta-cat mice and wild-type mice were cultured in vitro, and aggrecan catabolism was stimulated with either interleukin-1alpha (IL-1alpha) or retinoic acid. Total aggrecan release was measured, and aggrecanase activity was examined by Western blotting using neoepitope antibodies for detecting cleavage at EGE 373-374 ALG, SELE 1279-1280 GRG, FREEE 1467-1468 GLG, and AQE 1572-1573 AGEG. Aggrecan catabolism in vivo was examined by Western blotting of cartilage that had been extracted immediately ex vivo. TS-4/TS-5 Delta-cat mice were viable, fertile, and phenotypically normal. TS-4/TS-5 Delta-cat cartilage explants did not release aggrecan in response to IL-1alpha, and there was no detectable increase in aggrecanase neoepitopes. TS-4/TS-5 Delta-cat cartilage explants released aggrecan in response to retinoic acid. There was no retinoic acid-stimulated cleavage at either EGE 373-374 ALG or AQE 1572-1573 AGEG. There was a low level of cleavage at SELE 1279-1280 GRG and major cleavage at FREEE 1467-1468 GLG. Ex vivo, cleavage at FREEE 1467-1468 GLG was substantially reduced, but still present, in TS-4/TS-5 Delta-cat mouse cartilage compared with wild-type mouse cartilage. An aggrecanase other than ADAMTS-4 and ADAMTS-5 is expressed in mouse cartilage and is up-regulated by retinoic acid but not IL-1alpha. The novel aggrecanase appears to have different substrate specificity from either ADAMTS-4 or ADAMTS-5, cleaving E-G bonds but not E-A bonds. Neither ADAMTS-4 nor ADAMTS-5 is required for normal skeletal development or aggrecan turnover in cartilage.

  10. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

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    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hofmann, Matthias [Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt (Germany); Kusachi, Shozo [Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama (Japan); Ninomiya, Yoshifumi [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); Hirohata, Satoshi, E-mail: hirohas@cc.okayama-u.ac.jp [Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama (Japan); International Center, Okayama University, Okayama (Japan)

    2014-05-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC.

  11. ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

    International Nuclear Information System (INIS)

    Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; Asano, Keiichi; Faruk Hatipoglu, Omer; Zeynel Cilek, Mehmet; Obika, Masanari; Ohtsuki, Takashi; Hofmann, Matthias; Kusachi, Shozo; Ninomiya, Yoshifumi; Hirohata, Satoshi

    2014-01-01

    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy. - Highlights: • ADAMTS1 significantly inhibited tube formation and cell proliferation in HMVEC-dLy. • Reduced lymph endothelial cell migration in ADAMTS1 transduced co-culture systems. • VEGFC-stimulated phosphorylation of VEGFR3 is attenuated by ADAMTS1. • Reduced phosphorylation of Akt and ERK1/2 in ADAMTS1 treated HMVEC-dLy. • ADAMTS1 binds directly to VEGFC

  12. Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.

    Science.gov (United States)

    Ataca, Dalya; Caikovski, Marian; Piersigilli, Alessandra; Moulin, Alexandre; Benarafa, Charaf; Earp, Sarah E; Guri, Yakir; Kostic, Corinne; Arsenijevic, Yvan; Soininen, Raija; Apte, Suneel S; Brisken, Cathrin

    2016-11-15

    The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain 'orphan' proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E)13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis. © 2016. Published by The Company of Biologists Ltd.

  13. Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development

    Directory of Open Access Journals (Sweden)

    Dalya Ataca

    2016-11-01

    Full Text Available The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain ‘orphan’ proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis.

  14. The Investigation of ADAMTS16 in Insulin-Induced Human Chondrosarcoma Cells.

    Science.gov (United States)

    Cakmak, Ozlem; Comertoglu, Ismail; Firat, Ridvan; Erdemli, Haci Kemal; Kursunlu, S Fatih; Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Adam, Bahattin; Demircan, Kadir

    2015-08-01

    A disintegrin-like metalloproteinase with thrombospondin motifs (ADAMTS) is a group of proteins that have enzymatic activity secreted by cells to the outside extracellular matrix. Insulin induces proteoglycan biosynthesis in chondrosarcoma chondrocytes. The purpose of the present in vitro study is to assess the time course effects of insulin on ADAMTS16 expression in OUMS-27 (human chondrosarcoma) cell line to examine whether insulin regulates ADAMTS16 expression as well as proteoglycan biosynthesis with multifaceted properties or not. Chondrosarcoma cells were cultured in Dulbecco's modified Eagle's medium having either 10 μg/mL insulin or not. While the experiment was going on, the medium containing insulin had been changed every other day. Cells were harvested at 1st, 3rd, 7th, and 11th days; subsequently, RNA and proteins were isolated in every experimental group according to their time interval. RNA expression of ADAMTS was estimated by quantitative real-time polymerase chain reaction (qRT-PCR) by using primers. Immunoreactive protein levels were encountered by the western blot protein detection technique by using proper anti-ADAMTS16 antibodies. ADAMTS16 mRNA expression level of chondrosarcoma cells was found to be insignificantly decreased in chondrosarcoma cells induced by insulin detected by the qRT-PCR instrument. On the other hand, there was a gradual decrease in immune-reactant ADAMTS16 protein amount by the time course in insulin-treated cell groups when compared with control cells. It has been suggested that insulin might possibly regulate ADAMTS16 levels/activities in OUMS-27 chondrosarcoma cells taking a role in extracellular matrix turnover.

  15. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines

    International Nuclear Information System (INIS)

    Thirunavukkarasu, Kannan; Pei, Yong; Moore, Terry L.; Wang, He; Yu, Xiao-peng; Geiser, Andrew G.; Chandrasekhar, Srinivasan

    2006-01-01

    ADAMTS-4 (aggrecanase-1) is a metalloprotease that plays a role in aggrecan degradation in the cartilage extracellular matrix. In order to understand the regulation of ADAMTS-4 gene expression we have cloned and characterized a functional 4.5 kb human ADAMTS-4 promoter. Sequence analysis of the promoter revealed the presence of putative binding sites for nuclear factor of activated T cells (NFAT) and Runx family of transcription factors that are known to regulate chondrocyte maturation and differentiation. Using promoter-reporter assays and mRNA analysis we have analyzed the role of chondrocyte-expressed transcription factors NFATp and Runx2 and have shown that ADAMTS-4 is a potential downstream target of these two factors. Our results suggest that inhibition of the expression/function of NFATp and/or Runx2 may enable us to modulate aggrecan degradation in normal physiology and/or in degenerative joint diseases. The ADAMTS-4 promoter would serve as a valuable mechanistic tool to better understand the regulation of ADAMTS-4 expression by signaling pathways that modulate cartilage matrix breakdown

  16. Fluorescence Resonance Energy Transfer Assay for High-Throughput Screening of ADAMTS1 Inhibitors

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    Guanhua Du

    2011-12-01

    Full Text Available A disintegrin and metalloprotease with thrombospondin type I motifs-1 (ADAMTS1 plays a crucial role in inflammatory joint diseases and its inhibitors are potential candidates for anti-arthritis drugs. For the purposes of drug discovery, we reported the development and validation of fluorescence resonance energy transfer (FRET assay for high-throughput screening (HTS of the ADAMTS1 inhibitors. A FRET substrate was designed for a quantitative assay of ADAMTS1 activity and enzyme kinetics studies. The assay was developed into a 50-µL, 384-well assay format for high throughput screening of ADAMTS1 inhibitors with an overall Z’ factor of 0.89. ADAMTS1 inhibitors were screened against a diverse library of 40,960 total compounds with the established HTS system. Four structurally related hits, naturally occurring compounds, kuwanon P, kuwanon X, albafuran C and mulberrofuran J, extracted from the Chinese herb Morus alba L., were identified for further investigation. The results suggest that this FRET assay is an excellent tool, not only for measurement of ADAMTS1 activity but also for discovery of novel ADAMTS1 inhibitors with HTS.

  17. Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation

    OpenAIRE

    Enomoto, Hiroyuki; Nelson, Courtney M.; Somerville, Robert P. T.; Mielke, Katrina; Dixon, Laura J.; Powell, Kimerly; Apte, Suneel S.

    2010-01-01

    We have identified a role for two evolutionarily related, secreted metalloproteases of the ADAMTS family, ADAMTS20 and ADAMTS9, in palatogenesis. Adamts20 mutations cause the mouse white-spotting mutant belted (bt), whereas Adamts9 is essential for survival beyond 7.5 days gestation (E7.5). Functional overlap of Adamts9 with Adamts20 was identified using Adamts9+/–;bt/bt mice, which have a fully penetrant cleft palate. Palate closure was delayed, although eventually completed, in both Adamts9...

  18. ADAMTS-1 Is Found in the Nuclei of Normal and Tumoral Breast Cells.

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    Suély V Silva

    Full Text Available Proteins secreted in the extracellular matrix microenvironment (ECM by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs family have been implicated in tissue remodeling events observed in cancer development, growth and progression. Here we investigated the subcellular localization of ADAMTS-1 in normal-like (MCF10-A and tumoral (MCF7 and MDA-MB-231 human breast cells. ADAMTS-1 is a secreted protease found in the extracellular matrix. However, in this study we show for the first time that ADAMTS-1 is also present in the nuclei and nucleoli of the three mammary cell lines studied here. Our findings indicate that ADAMTS-1 has proteolytic functions in the nucleus through its interaction with aggrecan substrate.

  19. Identificaci?n de interacciones proteicas de ADAMTS19 en un contexto ov?rico

    OpenAIRE

    Festiva Mora, Mar?a Camila

    2017-01-01

    Las prote?nas ADAMTS (desintegrinas y metaloproteinasas con motivos trombospondina) han sido asociadas a diversos procesos biol?gicos entre ellos el desarrollo folicular y la ovulaci?n. Algunos miembros son considerados prote?nas hu?rfanas debido a que no se han descrito sus sustratos espec?ficos (e.g. ADAMTS19). Espec?ficamente ADAMTS19 ha sido sugerido recientemente como un gen candidato de FOP. En el presente trabajo se realiz? un tamizaje de las potenciales prote?nas de interacci?n (partn...

  20. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

    Directory of Open Access Journals (Sweden)

    Danielle N Drury-Stewart

    Full Text Available The coagulation protein von Willebrand Factor (VWF is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.We measured VWF antigen (VWF:Ag, VWF propeptide (VWFpp, Factor VIII (FVIII, and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF of VWF in two pregnancies which had samples from multiple trimesters.VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

  1. Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.

    Science.gov (United States)

    Nieves Torres, Evelyn C; Yang, Binxia; Roy, Bhaskar; Janardhanan, Rajiv; Brahmbhatt, Akshaar; Leof, Ed; Mukhopadhyay, Debabrata; Misra, Sanjay

    2014-01-01

    Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV-shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.

  2. Adventitial delivery of lentivirus-shRNA-ADAMTS-1 reduces venous stenosis formation in arteriovenous fistula.

    Directory of Open Access Journals (Sweden)

    Evelyn C Nieves Torres

    Full Text Available Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1 at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1 at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A and matrix metalloproteinase-9 (MMP-9 (LV-shRNA-ADAMTS-1 transduced vessels vs. controls. These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.

  3. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

    Science.gov (United States)

    Cataland, S R; Wu, H M

    2015-06-01

    Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

  4. Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-κB signaling.

    Science.gov (United States)

    Xu, Hongying; Xiao, Qian; Fan, Yu; Xiang, Tingxiu; Li, Chen; Li, Chunhong; Li, Shuman; Hui, Tianli; Zhang, Lu; Li, Hongzhong; Li, Lili; Ren, Guosheng

    2017-06-01

    ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70.8% of tumor tissues by methylation-specific PCR, but none of the normal tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in inhibition of cell migration and invasion. Nude mouse model further confirmed that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT), further inhibited migration and invasion of breast cancer cells. ADAMT18 deregulated AKT and NF-κB signaling, through inhibiting phosphorylation levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor antagonizes AKT and NF-κB signaling in breast tumorigenesis. Its methylation could be a potential tumor biomarker for breast cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  5. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

    Science.gov (United States)

    Wolf, Zena T; Brand, Harrison A; Shaffer, John R; Leslie, Elizabeth J; Arzi, Boaz; Willet, Cali E; Cox, Timothy C; McHenry, Toby; Narayan, Nicole; Feingold, Eleanor; Wang, Xioajing; Sliskovic, Saundra; Karmi, Nili; Safra, Noa; Sanchez, Carla; Deleyiannis, Frederic W B; Murray, Jeffrey C; Wade, Claire M; Marazita, Mary L; Bannasch, Danika L

    2015-03-01

    Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13); adjusted p= 2.2 x 10(-3)). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

  6. Epigenetic silencing of ADAMTS5 is associated with increased invasiveness and poor survival in patients with colorectal cancer.

    Science.gov (United States)

    Li, Jizhen; Liao, Yi; Huang, Jintuan; Sun, Yi; Chen, Hao; Chen, Chunyu; Li, Senmao; Yang, Zuli

    2018-02-01

    A disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p colorectal cancer, and correlates with OS and DFS, indicating that ADAMTS5 might be a useful biomarker in colorectal cancer therapy.

  7. ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling

    Directory of Open Access Journals (Sweden)

    Ling Chen

    2017-11-01

    Full Text Available Background/Aims: ADAMTS (disintegrin-like and metalloproteinase with thrombospondin motifs proteins are extracellular zinc metalloproteinases that play an important role in extracellular matrix assembly and degradation, connective tissue structuring, angiogenesis, and cell migration. Multiple studies suggest that ADAMTS proteins (e.g. ADAMTS9 can act as tumor suppressors. In gastric, esophageal, and nasopharyngeal carcinomas ADAMTS9 is frequently down-regulated by promoter methylation. Whether ADAMTS9 can function as a tumor suppressor gene (TSG in colorectal cancer is still unclear. Methods: We performed immunohistochemistry, RT-PCR, and qRT-PCR, to examine the expression of ADAMTS9 in colorectal cancer cell lines and primary colorectal cancer tissues. Methylation-specific PCR was also carried out to investigate the promoter methylation status of ADAMTS9. We also explored the functions of ADAMTS9 in colorectal cancer cell lines through in vitro experiments. Results: ADAMTS9 expression was down-requlated or silenced in 83.3% (5/6 of colorectal cancer cell lines, and frequently repressed in 65.6% (21/32 of colorectal cancer tissues. Down-regulation of ADAMTS9 was partially due to promoter methylation. Exogenous expression of ADAMTS9 in colorectal cancer cell lines inhibited cell proliferation and migration through the regulation of cell cycle and apoptosis. In addition, ADAMTS9 prevented the activation of Akt, and its downstream targets in colorectal cancer cell lines. Conclusion: Our findings suggest ADAMTS9 is a TSG in colorectal cancer.

  8. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.

    Directory of Open Access Journals (Sweden)

    Zena T Wolf

    2015-03-01

    Full Text Available Cleft lip with or without cleft palate (CL/P is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13; adjusted p= 2.2 x 10(-3. Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3, which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6 with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

  9. Identificación de interacciones proteicas de ADAMTS19 en un contexto ovárico

    OpenAIRE

    Festiva Mora, María Camila

    2017-01-01

    Las proteínas ADAMTS (desintegrinas y metaloproteinasas con motivos trombospondina) han sido asociadas a diversos procesos biológicos entre ellos el desarrollo folicular y la ovulación. Algunos miembros son considerados proteínas huérfanas debido a que no se han descrito sus sustratos específicos (e.g. ADAMTS19). Específicamente ADAMTS19 ha sido sugerido recientemente como un gen candidato de FOP. En el presente trabajo se realizó un tamizaje de las potenciales proteínas de interacción (partn...

  10. Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change.

    Directory of Open Access Journals (Sweden)

    Shiaw-Wei Tyan

    Full Text Available Microenvironment plays an important role in cancer development. We have reported that the cancer-associated stromal cells exhibit phenotypic and functional changes compared to stromal cells neighboring to normal tissues. However, the molecular mechanisms as well as the maintenance of these changes remain elusive. Here we showed that through co-culture with breast cancer cells for at least three to four passages, breast normal tissue-associated fibroblasts (NAFs gained persistent activity for promoting cancer cell invasion, partly via up-regulating ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1. Furthermore, we demonstrated that the DNA methylation pattern in the ADAMTS1 promoter has no alteration. Instead, the loss of EZH2 binding to the ADAMTS1 promoter and the resulting decrease of promoter-associated histone H3K27 methylation may account for the up-regulation of ADAMTS1. Importantly, the lack of EZH2 binding and the H3K27 methylation on the ADAMTS1 promoter were sustained in cancer cell-precocultured NAFs after removal of cancer cells. These results suggest that cancer cells are capable of inducing stromal fibroblasts to secrete ADAMTS1 persistently for their invasion and the effect is epigenetically inheritable.

  11. The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model

    DEFF Research Database (Denmark)

    He, Yi; Zheng, Qinlong; Simonsen, Ole

    2013-01-01

    of osteoarthritis stained strongly for active ADAMTS-4 where surface fibrillation and clustered chondrocytes were observed. This assay could be an effective tool for studying ADAMTS-4 activity and for screening drugs regulating ADAMTS-4 activation. Moreover, it could be a potential biomarker for degenerative joint...

  12. ADAMTS-7 Expression Increases in the Early Stage of Angiotensin II-Induced Renal Injury in Elderly Mice

    Directory of Open Access Journals (Sweden)

    Yan-Xiang Gao

    2014-03-01

    Full Text Available Background/Aims: We investigated the recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs, and matrix metalloproteinases (MMPs as inflammatory mediators in inflammatory kidney damage by studying ADAMTS-1, -4, and -7 and MMP-9 expression in elderly mouse kidneys after angiotensin II (Ang II administration. Methods: Ang II (2.5 µg/kg/min or norepinephrine (8.3 µg/kg/min was subcutaneously infused in old mice. Renal injury was assessed by hematoxylin-eosin staining, 24-h albuminuria, and immunohistochemistry to evaluate inflammatory cell markers. The mRNA and protein expression of ADAMTS-1, -4, and -7 and MMP-9 were determined using real-time PCR, Western blot, and immunohistochemistry 3 days after Ang II or norepinephrine administration. Results: Elderly mice in the Ang II group developed hypertension and pathological kidney damage. The mRNA and protein levels of ADAMTS-7 in the Ang II group were 3.3 ± 1.1 (P = 0.019 and 1.6 ± 0.1 (P = 0.047 vs. 1.0 ± 0.1 and 1.0 ± 0.1 in the control group on day 3. In contrast, treatment with the hypertensive agent norepinephrine did not lead to obvious renal damage or an increase in renal ADAMTS-7 expression. Conclusions: Renal ADAMTS-7 expression was induced by Ang II in elderly mice. The overexpression of ADATMTS-7 might contribute to early inflammatory kidney damage associated with aging.

  13. Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in Altered Lifespan and Dauer Formation.

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    Sawako Yoshina

    Full Text Available ADAMTS9 is a metalloprotease that cleaves components of the extracellular matrix and is also implicated in transport from the endoplasmic reticulum (ER to the Golgi. It has been reported that an ADAMTS9 gene variant is associated with type 2 diabetes. The underlying pathology of type 2 diabetes is insulin resistance and beta-cell dysfunction. However, the molecular mechanisms underlying ADAMTS9 function in beta cells and peripheral tissues are unknown. We show that loss of C. elegans GON-1, an ADAMTS9 homolog, alters lifespan and dauer formation. GON-1 loss impairs secretion of proteins such as insulin orthologs and TGF-beta, and additionally impacts insulin/IGF-1 signaling in peripheral tissues. The function of the GON domain, but not the protease domain, is essential for normal lifespan and dauer formation in these scenarios. We conclude that the GON domain is critical for ADAMTS9/GON-1 function across species, which should help the understanding of type 2 diabetes in humans.

  14. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

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    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  15. Versican Proteolysis by ADAMTS Proteases and Its Influence on Sex Steroid Receptor Expression in Uterine Leiomyoma.

    Science.gov (United States)

    Gueye, Ndeye-Aicha; Mead, Timothy J; Koch, Christopher D; Biscotti, Charles V; Falcone, Tommaso; Apte, Suneel S

    2017-05-01

    Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. We investigated ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs) protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and RNA in situ hybridization for analysis of myometrium, leiomyoma and immortalized myometrium and leiomyoma cells. Short interfering RNA (siRNA) was used to knockdown versican in leiomyoma cells. This study was performed in an academic laboratory. Study subjects were women with symptomatic or asymptomatic leiomyoma. We quantified messenger RNAs (mRNAs) for versican splice variants. We identified ADAMTS-cleaved versican in myometrium and leiomyoma and ADAMTS messenger RNAs and examined the effect of VCAN siRNA on smooth muscle differentiation and expression of estrogen and progesterone receptors. The women in the symptomatic group (n = 7) had larger leiomyoma (P = 0.01), heavy menstrual bleeding (P leiomyomas of symptomatic versus asymptomatic women (P = 0.03 and P = 0.04, respectively). Abundant cleaved versican was detected in leiomyoma and myometrium, as well as in myometrial and leiomyoma cell lines. ADAMTS4 (P = 0.03) and ADAMTS15 (P = 0.04) were upregulated in symptomatic leiomyomas. VCAN siRNA did not effect cell proliferation, apoptosis, or smooth muscle markers, but reduced ESR1 and PR-A expression (P = 0.001 and P = 0.002, respectively). Versican in myometrium, leiomyomas and in the corresponding immortalized cells is cleaved by ADAMTS proteases. VCAN siRNA suppresses production of estrogen receptor 1 and progesterone receptor-A. These findings have implications for leiomyoma growth. Copyright © 2017 by the Endocrine Society

  16. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

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    Shuo Liu

    Full Text Available Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases

  17. Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

    Science.gov (United States)

    Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

    2015-01-01

    Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

  18. Loss of ADAMTS5 enhances brown adipose tissue mass and promotes browning of white adipose tissue via CREB signaling

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    Dries Bauters

    2017-07-01

    Conclusions: These data indicate that ADAMTS5 plays a functional role in development of BAT and browning of WAT. Hence, selective targeting of ADAMTS5 could provide a novel therapeutic strategy for treatment/prevention of obesity and metabolic diseases.

  19. The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Tauchi Ryoji

    2012-03-01

    Full Text Available Abstract Background Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use. Methods The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed. Results ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury. Conclusions Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.

  20. Severe recurrent achalasia cardia responding to treatment of severe autoimmune acquired haemophilia

    OpenAIRE

    Al-Jafar, H; Laffan, M; Al-Sabah, S; Elmorsi, M; Habeeb, M; Alnajar, F

    2012-01-01

    Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesopha...

  1. Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.

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    James A C Oliver

    Full Text Available Mutations in ADAMTS10 (CFA20 have previously been associated with primary open angle glaucoma (POAG in the Beagle and Norwegian Elkhound. The closely related gene, ADAMTS17, has also been associated with several different ocular phenotypes in multiple breeds of dog, including primary lens luxation and POAG. We investigated ADAMTS17 as a candidate gene for POAG in the Basset Hound and Basset Fauve de Bretagne dog breeds.We performed ADAMTS17 exon resequencing in three Basset Hounds and three Basset Fauve de Bretagne dogs with POAG. Identified variants were genotyped in additional sample cohorts of both breeds and dogs of other breeds to confirm their association with disease.All affected Basset Hounds were homozygous for a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein. Fifty clinically unaffected Basset Hounds were genotyped for this mutation and all were either heterozygous or homozygous for the wild type allele. Genotyping of 223 Basset Hounds recruited for a different study revealed a mutation frequency of 0.081 and predicted frequency of affected dogs in the population to be 0.007. Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 1.26 x 10-10. All affected Basset Fauve de Bretagne dogs were homozygous for a missense mutation in exon 11 causing a glycine to serine amino acid substitution (G519S in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function. Unaffected Basset Fauve de Bretagne dogs were either heterozygous for the mutation (5/24 or homozygous for the wild type allele (19/24. Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 2.80 x 10-7. Genotyping of 85 dogs of unrelated breeds and 90 dogs of related breeds for this variant was negative.This report documents strong associations between two independent ADAMTS17 mutations and POAG in two

  2. Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.

    Science.gov (United States)

    Oliver, James A C; Forman, Oliver P; Pettitt, Louise; Mellersh, Cathryn S

    2015-01-01

    Mutations in ADAMTS10 (CFA20) have previously been associated with primary open angle glaucoma (POAG) in the Beagle and Norwegian Elkhound. The closely related gene, ADAMTS17, has also been associated with several different ocular phenotypes in multiple breeds of dog, including primary lens luxation and POAG. We investigated ADAMTS17 as a candidate gene for POAG in the Basset Hound and Basset Fauve de Bretagne dog breeds. We performed ADAMTS17 exon resequencing in three Basset Hounds and three Basset Fauve de Bretagne dogs with POAG. Identified variants were genotyped in additional sample cohorts of both breeds and dogs of other breeds to confirm their association with disease. All affected Basset Hounds were homozygous for a 19 bp deletion in exon 2 that alters the reading frame and is predicted to lead to a truncated protein. Fifty clinically unaffected Basset Hounds were genotyped for this mutation and all were either heterozygous or homozygous for the wild type allele. Genotyping of 223 Basset Hounds recruited for a different study revealed a mutation frequency of 0.081 and predicted frequency of affected dogs in the population to be 0.007. Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 1.26 x 10-10. All affected Basset Fauve de Bretagne dogs were homozygous for a missense mutation in exon 11 causing a glycine to serine amino acid substitution (G519S) in the disintegrin-like domain of ADAMTS17 which is predicted to alter protein function. Unaffected Basset Fauve de Bretagne dogs were either heterozygous for the mutation (5/24) or homozygous for the wild type allele (19/24). Based on the entire genotyping dataset the association statistic for the POAG-associated deletion was p = 2.80 x 10-7. Genotyping of 85 dogs of unrelated breeds and 90 dogs of related breeds for this variant was negative. This report documents strong associations between two independent ADAMTS17 mutations and POAG in two different

  3. Severe Recurrent Achalasia Cardia Responding to Treatment of Severe Autoimmune Acquired Haemophilia

    Directory of Open Access Journals (Sweden)

    H. Al-Jafar

    2012-09-01

    Full Text Available Acquired haemophilia A and severe acquired achalasia are both very rare conditions with unknown aetiology. Haemophilia A is a haemorrhagic disease induced by deficiency or malfunction of coagulation factor VIII. Congenital haemophilia is an inherited disease transmitted by the mother through X-linked inheritance and primarily affects males. However, acquired haemophilia A is a serious, sudden-onset, autoimmune disease that affects either sex. In addition, achalasia is a disease of the oesophagus caused by abnormal function of the nerves and muscles. It causes swallowing difficulties due to the inability of the lower oesophageal sphincter to relax during swallowing, leading to dysphagia, regurgitation and chest pain. In this report, we describe the case of a patient with severe, newly diagnosed, acquired haemophilia A with long-standing, recurrent achalasia; the achalasia had recurred 3 times despite complete and proper surgical fixation. Acquired haemophilia A is treated with immunosuppressive therapy. High-dose steroid therapy was administered for 7 months, during which the patient responded well; moreover, the achalasia did not recur for more than 2 years. The response of the achalasia to immunosuppressive therapy suggests that achalasia may be an autoimmune disorder and that there may be an association between both diseases. The findings of the present case suggest that achalasia may favourably respond to steroid therapy as a first-line treatment prior to surgery.

  4. Ny markør ved trombotisk trombocytopenisk purpura

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Hillarp, Andreas; Lindblom, Anders

    2008-01-01

    Thrombotic microangiopathy can be caused by several conditions which are difficult to diagnose from the clinical presentation alone. Deficient enzyme activity of a newly-discovered enzyme, ADAMTS-13, can lead to thrombotic thrombocytopenic purpura (TTP). Lack of ADAMTS-13 activity causes increased...

  5. [New marker in thrombotic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Hillarp, A.; Lindblom, A.; Bjork, P.

    2008-01-01

    Thrombotic microangiopathy can be caused by several conditions which are difficult to diagnose from the clinical presentation alone. Deficient enzyme activity of a newly-discovered enzyme, ADAMTS-13, can lead to thrombotic thrombocytopenic purpura (TTP). Lack of ADAMTS-13 activity causes increased...

  6. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets.

    Science.gov (United States)

    Bekhouche, Mourad; Leduc, Cedric; Dupont, Laura; Janssen, Lauriane; Delolme, Frederic; Vadon-Le Goff, Sandrine; Smargiasso, Nicolas; Baiwir, Dominique; Mazzucchelli, Gabriel; Zanella-Cleon, Isabelle; Dubail, Johanne; De Pauw, Edwin; Nusgens, Betty; Hulmes, David J S; Moali, Catherine; Colige, Alain

    2016-05-01

    A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2, 3, and 14 are collectively named procollagen N-proteinases (pNPs) because of their specific ability to cleave the aminopropeptide of fibrillar procollagens. Several reports also indicate that they could be involved in other biological processes, such as blood coagulation, development, and male fertility, but the potential substrates associated with these activities remain unknown. Using the recently described N-terminal amine isotopic labeling of substrate approach, we analyzed the secretomes of human fibroblasts and identified 8, 17, and 22 candidate substrates for ADAMTS2, 3, and 14, respectively. Among these newly identified substrates, many are components of the extracellular matrix and/or proteins related to cell signaling such as latent TGF-β binding protein 1, TGF-β RIII, and dickkopf-related protein 3. Candidate substrates for the 3 ADAMTS have been biochemically validated in different contexts, and the implication of ADAMTS2 in the control of TGF-β activity has been further demonstrated in human fibroblasts. Finally, the cleavage site specificity was assessed showing a clear and unique preference for nonpolar or slightly hydrophobic amino acids. This work shows that the activities of the pNPs extend far beyond the classically reported processing of the aminopropeptide of fibrillar collagens and that they should now be considered as multilevel regulators of matrix deposition and remodeling.-Bekhouche, M., Leduc, C., Dupont, L., Janssen, L., Delolme, F., Vadon-Le Goff, S., Smargiasso, N., Baiwir, D., Mazzucchelli, G., Zanella-Cleon, I., Dubail, J., De Pauw, E., Nusgens, B., Hulmes, D. J. S., Moali, C., Colige, A. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets. © FASEB.

  7. Prognostic value of lactate clearance in severe community acquired pneumonia

    OpenAIRE

    Mohamed, Kamel Abd Elaziz; Ahmed, Dief Abd Elgalil

    2014-01-01

    Introduction: Severe community acquired pneumonia (SCAP) occurs in approximately 18–36% of all CAP and the mortality rate could be as high as 67% in patients with SCAP. Several studies have described a correlation between baseline lactate concentration and mortality of ICU patients. Aim of the work: To follow lactate clearance after admission for 24 h which could be an indicator of outcome in severe community acquired pneumonia. Patients and methods: Forty-six consecutively admitted adu...

  8. Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy.

    Science.gov (United States)

    Vesely, S K

    2015-06-01

    Patients who have recovered from their acute episode of acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery. © 2015 International Society on Thrombosis and Haemostasis.

  9. Тhe features of severe community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Avramenko I.V.

    2015-06-01

    Full Text Available Based on data from a prospective analysis for the year of observation, the article presents information about the features of severe community acquired pneumonia in patients who were hospitalized at the department of pulmonology (or therapy, as well as department of the intensive care from three teaching hospitals in Dnepropetrovsk, namely "Dnipropetrovsk City Hospital №6», "Dnipropetrovsk City Hospital №2», "Dnipropetrovsk City Hospital №16», which are the clinical ones of "Dnepropetrovsk Medical Academy of the Ministry of Health Ukraine". Dependence of the severity of the condition shown on duration of illness before admission, features of season character of disease. The effect of breathing exercises on the course of the disease. The results can be the basis for a more personal approach to the development of diagnostic and therapeutic programs for patients with severe community-acquired pneumonia.

  10. Trombotisk trombocytopenisk purpura hos barn med lavt ADAMTS13 enzymniveau

    DEFF Research Database (Denmark)

    Spangenberg, Katrine Bredsdorff; Clasen-Linde, Erik; Poulsen, Anja

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare condition, but important to consider in case of thrombocytopenia and haemolysis. It is imperative to proceed with the correct treatment, in order to ensure a satisfactory outcome. TTP is either acquired or idiopathic. This case report shows...

  11. A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Arimoto M

    2012-03-01

    Full Text Available Miyoko Arimoto1, Yutaka Komiyama2, Fumiko Okamae1, Akemi Ichibe1, Setsuko Teranishi1, Hirohiko Tokunaga1, Keiko Nakaya3, Michie Fujiwara3, Manabu Yamaoka4, Shuji Onishi4, Rie Miyamoto5, Naoto Nakamichi5, Shosaku Nomura51Blood Transfusion Unit, Kansai Medical University Takii Hospital, 2Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 3Clinical Medical Technology Unit, Kansai Medical University Takii Hospital, 4Blood Transfusion Unit, Kansai Medical University Hirakata Hospital, 5First Department of Internal Medicine, Kansai Medical University, Moriguchi, JapanAbstract: Thrombotic thrombocytopenic purpura (TTP is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, acute pancreatitis, plasma exchange

  12. Prognostic value of severity indicators of nursing-home-acquired pneumonia versus community-acquired pneumonia in elderly patients

    Directory of Open Access Journals (Sweden)

    Ugajin M

    2014-02-01

    Full Text Available Motoi Ugajin, Kenichi Yamaki, Natsuko Hirasawa, Takanori Kobayashi, Takeo Yagi Department of Respiratory Medicine, Ichinomiya-Nishi Hospital, Ichinomiya City, Japan Background: The credibility of prognostic indicators in nursing-home-acquired pneumonia (NHAP is not clear. We previously reported a simple prognostic indicator in community-acquired pneumonia (CAP: blood urea nitrogen to serum albumin (B/A ratio. This retrospective study investigated the prognostic value of severity indicators in NHAP versus CAP in elderly patients. Methods: Patients aged ≥65 years and hospitalized because of NHAP or CAP within the previous 3 years were enrolled. Demographics, coexisting illnesses, laboratory and microbiological findings, and severity scores (confusion, urea, respiratory rate, blood pressure, and age ≥65 [CURB-65] scale; age, dehydration, respiratory failure, orientation disturbance, and pressure [A-DROP] scale; and pneumonia severity index [PSI] were retrieved from medical records. The primary outcome was mortality within 28 days of admission. Results: In total, 138 NHAP and 307 CAP patients were enrolled. Mortality was higher in NHAP (18.1% than in CAP (4.6% (P<0.001. Patients with NHAP were older and had lower functional status and a higher rate of do-not-resuscitate orders, heart failure, and cerebrovascular diseases. The NHAP patients more frequently had typical bacterial pathogens. Using the receiver-operating characteristics curve for predicting mortality, the area under the curve in NHAP was 0.70 for the A-DROP scale, 0.69 for the CURB-65 scale, 0.67 for the PSI class, and 0.65 for the B/A ratio. The area under the curve in CAP was 0.73 for the A-DROP scale, 0.76 for the CURB-65 scale, 0.81 for the PSI class, and 0.83 for the B/A ratio. Conclusion: Patient mortality was greater in NHAP than in CAP. Patient characteristics, coexisting illnesses, and detected pathogens differed greatly between NHAP and CAP. The existing severity indicators

  13. A Study of Emotionalism in Patients Undergoing Rehabilitation following Severe Acquired Brain Injury

    Directory of Open Access Journals (Sweden)

    Joanna McGrath

    2000-01-01

    Full Text Available The present study describes the phenomenon of emotionalism in a sample of brain injured patients of mixed aetiology, with a view to identifying issues relevant to clinical management, and possible causal factors. 82 subjects with severe acquired brain injury undergoing rehabilitation participated in a structured interview in which they were asked to report the presence/absence of emotionalism and degree of distress associated with it. Their overt crying behaviour was also observed and recorded. Independent variables that predicted crying during the interview were identified using a multiple logistic regression procedure. Prevalence rates of emotionalism-tearfulness were high in this sample (52% self-report, 36–41% Emotionalism-laughter was much less common (13% Emotionalism-tearfulness was usually accompanied by negative affect, occurred in response to identifiable precipitants, and was often controllable. It was associated with major personal distress in about half the subjects who reported it. Independent variables which predicted crying behaviour were female gender and focal damage to the right cerebral hemisphere. It is concluded that an increased readiness to cry is common in people with severe acquired brain injury of mixed aetiology. The behaviour is meaningful, though not always distressing. The intensity of the behaviour is variable, and it may be most appropriate to regard emotionalism as a dimension rather than a syndrome. Implications for clinical management are discussed.

  14. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

    Science.gov (United States)

    Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

    2015-02-01

    Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency ( 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

  15. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients.

    Science.gov (United States)

    Fujimura, Yoshihiro; Matsumoto, Masanori; Kokame, Koichi; Isonishi, Ayami; Soejima, Kenji; Akiyama, Nobu; Tomiyama, Junji; Natori, Kazuhiko; Kuranishi, Yasunobu; Imamura, Yutaka; Inoue, Nobumasa; Higasa, Satoshi; Seike, Masako; Kozuka, Teruhiko; Hara, Masamichi; Wada, Hideo; Murata, Mitsuru; Ikeda, Yasuo; Miyata, Toshiyuki; George, James N

    2009-03-01

    Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but its clinical signs may be mild or absent during childhood. We have identified 37 patients with USS (24 females, 13 males) belonging to 32 families. The nine women from six families who were diagnosed during their first pregnancy are the focus of this report. Six of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the second-third trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after birth, and the remaining seven were all premature except one, who was born naturally following plasma infusions to the mother that had started at 8 weeks' gestation. All nine USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated that eight women were compound heterozygotes of Y304C/G525D (2 siblings), R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has been previously reported. These observations emphasize the importance of measuring ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and pregnancy.

  16. Limitations of ADAMTS-13 activity level in diagnosing thrombotic thrombocytopenic purpura in pregnancy.

    Science.gov (United States)

    Ehsanipoor, Robert M; Rajan, Priya; Holcombe, Randall F; Wing, Deborah A

    2009-10-01

    In pregnancy, it may be difficult to differentiate the syndrome of hemolysis, elevated liver enzymes, and low platelets from thrombotic thrombocytopenia purpura. Severely depressed (present a case of a patient that presented at 20 weeks gestation with elevated liver enzymes and thrombocytopenia. The diagnosis was unclear at the time of presentation. She underwent induction of labor, and during the postpartum course, she was eventually diagnosed with thrombotic thrombocytopenia purpura; however, her activity level of a disintegrin and metalloproteinase with thrombospondin motifs-13 was only moderately depressed at 15% (normal pregnancy value 41%-105%).

  17. Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

    DEFF Research Database (Denmark)

    Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne

    2015-01-01

    BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate...... that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. METHODS: Cerebral energy metabolism was monitored in 15 patients with severe...... community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

  18. Social skills treatment for people with severe, chronic acquired brain injuries: a multicenter trial.

    Science.gov (United States)

    McDonald, Skye; Tate, Robyn; Togher, Leanne; Bornhofen, Cristina; Long, Esther; Gertler, Paul; Bowen, Rebecca

    2008-09-01

    To determine whether social skills deficits including unskilled, inappropriate behavior, problems reading social cues (social perception), and mood disturbances (such as depression and anxiety) could be remediated after severe traumatic brain injuries. Randomized controlled trial comparing a social skills program with social activity alone or with waitlist control. Several participants were reassigned after randomization. Hospital outpatient and community facilities. Fifty-one outpatients from 3 brain injury units in Sydney, Australia, with severe, chronic acquired brain injuries were recruited. A total of 39 people (13 in skills training, 13 in social activity, 13 in waitlist) completed all phases of the study. Twelve-week social skills treatment program encompassing weekly 3-hour group sessions focused on shaping social behavior and remediating social perception and 1-hour individual sessions to address psychologic issues with mood, self-esteem, etc. Primary outcomes were: (1) social behavior during encounters with a confederate as rated on the Behaviorally Referenced Rating System of Intermediary Social Skills-Revised (BRISS-R), (2) social perception as measured by The Awareness of Social Inference Test, and (3) depression and anxiety as measured by the Depression, Anxiety and Stress Scale. Secondary outcomes were: relative report on social behavior and participation using: the Katz Adjustment Scale-R1; the Social Performance Survey Schedule; the La Trobe Communication Questionnaire; and the Sydney Psychosocial Reintegration Scale (both relative and self-report). Repeated-measures analysis of variance indicated that social activity alone did not lead to improved performance relative to waitlist (placebo effect) on any outcome variable. On the other hand, the skills training group improved differentially on the Partner Directed Behavior Scale of the BRISS-R, specifically the self-centered behavior and partner involvement behavior subscales. No treatment effects

  19. Prognostic value of severity indicators of nursing-home-acquired pneumonia versus community-acquired pneumonia in elderly patients.

    Science.gov (United States)

    Ugajin, Motoi; Yamaki, Kenichi; Hirasawa, Natsuko; Kobayashi, Takanori; Yagi, Takeo

    2014-01-01

    The credibility of prognostic indicators in nursing-home-acquired pneumonia (NHAP) is not clear. We previously reported a simple prognostic indicator in community-acquired pneumonia (CAP): blood urea nitrogen to serum albumin (B/A) ratio. This retrospective study investigated the prognostic value of severity indicators in NHAP versus CAP in elderly patients. Patients aged ≥65 years and hospitalized because of NHAP or CAP within the previous 3 years were enrolled. Demographics, coexisting illnesses, laboratory and microbiological findings, and severity scores (confusion, urea, respiratory rate, blood pressure, and age ≥65 [CURB-65] scale; age, dehydration, respiratory failure, orientation disturbance, and pressure [A-DROP] scale; and pneumonia severity index [PSI]) were retrieved from medical records. The primary outcome was mortality within 28 days of admission. In total, 138 NHAP and 307 CAP patients were enrolled. Mortality was higher in NHAP (18.1%) than in CAP (4.6%) (Pscale, 0.69 for the CURB-65 scale, 0.67 for the PSI class, and 0.65 for the B/A ratio. The area under the curve in CAP was 0.73 for the A-DROP scale, 0.76 for the CURB-65 scale, 0.81 for the PSI class, and 0.83 for the B/A ratio. Patient mortality was greater in NHAP than in CAP. Patient characteristics, coexisting illnesses, and detected pathogens differed greatly between NHAP and CAP. The existing severity indicators had less prognostic value for NHAP than for CAP.

  20. Regulated expression of ADAMTS family members in follicles and cumulus oocyte complexes : evidence for specific and redundant patterns during ovulation

    NARCIS (Netherlands)

    Richards, JoAnne S; Hernandez-Gonzalez, Immaculada; Gonzalez-Robayna, Ignacio; Teuling, Eva; Lo, Yuet; Boerboom, Derek; Falender, Allison E; Doyle, Kari H; LeBaron, Richard G; Thompson, Vivian; Sandy, John D

    Protease cascades are essential for many biological events, including the LH-induced process of ovulation. ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin-like repeats-1) is expressed and hormonally regulated in the ovary by LH and the progesterone receptor. To determine whether

  1. Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    John Kuchtey

    2011-02-01

    Full Text Available Primary open angle glaucoma (POAG is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies.

  2. Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review

    Directory of Open Access Journals (Sweden)

    Claire Rouzaud

    2015-12-01

    Full Text Available Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi’s granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency.

  3. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli – An Anti-thrombotic Mechanism in the Kidney

    Directory of Open Access Journals (Sweden)

    Ramesh Tati

    2017-02-01

    Full Text Available Adequate cleavage of von Willebrand factor (VWF prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3, cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  4. Acquired Severe Disabilities and Complex Health Care Needs: Access to Inclusive Education

    Science.gov (United States)

    Ballard, Sarah L.; Dymond, Stacy K.

    2016-01-01

    This case study examined one high school student's access to inclusive education and experiences in an inclusive English class after he acquired severe disabilities and complex health care needs from a nontraumatic brain injury. Multiple sources of data (i.e., interviews, field notes, and documents) were collected and analyzed to formulate…

  5. Patients with severe acquired brain injury show increased arousal in tilt-table training

    DEFF Research Database (Denmark)

    Riberholt, Christian G; Thorlund, Jonas Bloch; Mehlsen, Jesper

    2013-01-01

    Patients with severe acquired brain injury (ABI) are often mobilised using a tilt-table. Complications such as orthostatic intolerance have been reported. The primary objective of this study was to investigate if using a tilt-table was feasible for mobilising patients with severe ABI admitted...... for sub-acute rehabilitation. We also investigated change in arousal, treatment duration before termination due to orthostatic reactions and change in muscle tone....

  6. ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting

    Directory of Open Access Journals (Sweden)

    Ehsan Valavi

    2011-01-01

    Full Text Available Hemiscorpius lepturus is a lethal scorpion with potentially cytotoxic venom. Various degrees of local and systemic toxicity have been observed after its envenomation ranging from local erythema to disseminated intravascular coagulation, renal failure and severe pulmonary hemorrhage. In this case report, we report on a seven-year-old patient who developed the hemolytic uremic syndrome (HUS after being stung by the scorpion H. lepturus. This condition is characterized by microangiopathic hemolytic anemia, thrombocytopenia, increased serum levels of lactate dehydrogenase and uremia. We evaluated the causes of HUS and found that the levels of C3, C4, CH50 and H factors were normal, but the activity of Von Willebrand factor cleaving protease was decreased (less than 5% of the normal activity. The patient improved after administering therapy with plasma exchange.

  7. Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

    Science.gov (United States)

    Nieto-Ríos, John Fredy; Álvarez Barreneche, María Fernanda; Penagos, Sara Catalina; Bello Márquez, Diana Carolina; Serna-Higuita, Lina Maria; Ramírez Sánchez, Isabel Cristina

    2018-02-01

    Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Mancini, I; Ricaño-Ponce, I; Pappalardo, E; Cairo, A; Gorski, M M; Casoli, G; Ferrari, B; Alberti, M; Mikovic, D; Noris, M; Wijmenga, C; Peyvandi, F

    2016-12-01

    Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura SUMMARY: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case-control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02-3.27, P = 1.64 × 10 -14 ). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10 -5 to 7.60 × 10 -5 ). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10 -19 ). Imputation of classic

  9. Expression Pattern of Human ADAMTS-2 (A disintegrin and metalloproteinase with thrombospondin motif, 2) in Different Cell Lines

    OpenAIRE

    ALPER, Meltem; KÖÇKAR, Feray

    2013-01-01

    The ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are a family of metalloproteases that are found in mammals and invertebrates. This family is known to influence development, angiogenesis, coagulation and progression of arthritis. ADAMTS2 plays an essential role in the processing of the fibrillar collagen precursors into mature collagen molecules by cleaving of the amino terminus of the type I, II, III and V procollagen molecules. Collagens are the most abundant and...

  10. A case of refractory thrombotic thrombocytopenic purpura treated ...

    African Journals Online (AJOL)

    Background. Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threaten- ing disorder that occurs due to deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member. 13), which is a von Willebrand factor (VWF) cleaving protein.[1]. The absent or severely reduced activity ...

  11. Perceived difficulty in use of everyday technology in persons with acquired brain injury of different severity: a comparison with controls.

    Science.gov (United States)

    Fallahpour, Mandana; Kottorp, Anders; Nygård, Louise; Lund, Maria Larsson

    2014-07-01

    To compare the perceived difficulty in use of everyday technology in persons with acquired brain injury with different levels of severity of disability with that of controls. This comparison study recruited 2 samples of persons with acquired brain injury and controls, comprising a total of 161 participants, age range 18-64 years. The long and short versions of the Everyday Technology Use Questionnaire and the Extended Glasgow Outcome Scale were used to evaluate participants. Persons with acquired brain injury demonstrated lower mean levels of perceived ability in use of everyday technology than controls (F = 21.84, degrees of freedom = 1, p technology between persons with severe disability and good recovery, between persons with severe disability and controls, and between persons with moderate disability and controls. No significant mean difference was found between persons with severe disability and moderate disability, between persons with moderate disability and good recovery, and between persons with good recovery and controls. Perceived difficulty in using everyday technology is significantly increased among persons with acquired brain injury with severe to moderate disability compared with controls. Rehabilitation services should consider the use of everyday technology in order to increase participation in everyday activities after acquired brain injury.

  12. [Multi-facetted clinical presentation of thrombotic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Niemann, C.U.; Jurlander, J.; Daugaard, G.

    2009-01-01

    smears. Determination of the ADAMTS13-activity is now becoming available as a routine analysis. We present two cases that illustrate the multi-facetted clinical presentation under which TTP occurs. The importance of access to ADAMTS13 measurements is stressed Udgivelsesdato: 2009/1/26...

  13. Cosmic ray runs acquired with ATLAS muon stations

    CERN Multimedia

    Cerutti, F.

    Starting in the fall 2005 several cosmic ray runs have been acquired in the ATLAS pit with six muon stations. These were three large outer and three large middle chambers of the feet sector (sector 13) that have been readout in the ATLAS cavern. In the first data taking period the trigger was based on two large scintillators (~300x30 cm2) positioned in sector 13 just below the large chambers. In this first run the precision chambers (the Monitored Drift Tubes) were operated in a close to final configuration. Typical trigger rates with this setup were of the order of 1 Hz. Several data sets of 10k events were acquired with final electronics up to the muon ROD and analysed with ATHENA-based software. These data allowed the first checks of the functionality and efficiency of the MDT stations in the ATLAS pit and the first measurement of the FE electronics noise in the ATLAS environment. A few event were also collected in a combined run with the TILE barrel calorimeter. An event display of a cosmic ray a...

  14. Treatment of acquired arteriovenous fistula with severe hemodynamic effects: therapeutic challenge

    Directory of Open Access Journals (Sweden)

    Bruna Ferreira Pilan

    2014-03-01

    Full Text Available A 34-year-old female patient with severe heart failure and pulmonary hypertension was diagnosed late with a high-output acquired arteriovenous fistula between the right common iliac vein and artery. The most probable cause was an iatrogenic vascular injury inflicted during a prior laparoscopic cholecystectomy. Treatment was conducted by placement of an endoprosthesis in the common iliac artery, achieving total exclusion of the fistula and complete remission of symptoms. Considering the options available for treating this type of lesion, endovascular techniques are becoming ever more effective and are now the option of first-choice for management of this pathology.

  15. Short- and long-term mortality in patients with community-acquired severe sepsis and septic shock

    DEFF Research Database (Denmark)

    Storgaard, Merete; Hallas, Jesper; Gahrn-Hansen, Bente

    2013-01-01

    Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population-based re......Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population...... extracted from the National Danish Patient Registry. We analyzed the hazard ratio for mortality at predefined intervals. Results: Absolute mortality within the first 30 days was 69/211 (33%, 95% confidence interval (CI) 25-41%), with a cumulative mortality of 121/211 (57%, 95% CI 48-69%) for the entire...... follow-up. Among septic patients who survived the first 30 days, the mortality hazard ratio was 2.7 (95% CI 1.7-4.3) until day 365, and among septic patients who survived the first year, the 1-4 y mortality hazard ratio was 2.3 (95% CI 1.7-3.3), compared to the community-based reference persons...

  16. Protéolyse du facteur Willebrand et cardiopathies à forces de cisaillement élevées : nouvelles approches diagnostiques et thérapeutiques

    OpenAIRE

    Rauch , Antoine

    2014-01-01

    In the first part of the thesis, we describe a novel approach based on antibody-based therapy to prevent the acquired von Willebrand factor (VWF) degradation observed in continuous-flow mechanical circulatory assist device therapy. Via a murine monoclonal antibody directed against VWF D4 domain and thus interfering with VWF-ADAMTS13 binding, a partial inhibition of VWF degradation is observed in whole blood using an ex vivo circulatory assist device model. In the second part of the thesis, we...

  17. Respiratory viruses among children with non-severe community-acquired pneumonia: A prospective cohort study.

    Science.gov (United States)

    Nascimento-Carvalho, Amanda C; Vilas-Boas, Ana-Luisa; Fontoura, Maria-Socorro H; Vuorinen, Tytti; Nascimento-Carvalho, Cristiana M

    2018-06-06

    Community-acquired pneumonia (CAP) causes a major burden to the health care system among children under-5 years worldwide. Information on respiratory viruses in non-severe CAP cases is scarce. To estimate the frequency of respiratory viruses among non-severe CAP cases. Prospective study conducted in Salvador, Brazil. Out of 820 children aged 2-59 months with non-severe CAP diagnosed by pediatricians (respiratory complaints and radiographic pulmonary infiltrate/consolidation), recruited in a clinical trial (ClinicalTrials.gov Identifier NCT01200706), nasopharyngeal aspirate samples were obtained from 774 (94.4%) patients and tested for 16 respiratory viruses by PCRs. Viruses were detected in 708 (91.5%; 95%CI: 89.3-93.3) cases, out of which 491 (69.4%; 95%CI: 65.9-72.7) harbored multiple viruses. Rhinovirus (46.1%; 95%CI: 42.6-49.6), adenovirus (38.4%; 95%CI: 35.0-41.8), and enterovirus (26.5%; 95%CI: 23.5-29.7) were the most commonly found viruses. The most frequent combination comprised rhinovirus plus adenovirus. No difference was found in the frequency of RSVA (16.1% vs. 14.6%; P = 0.6), RSVB (10.9% vs. 13.2%; P = 0.4) influenza (Flu) A (6.3% vs. 5.1%; P = 0.5), FluB (4.5% vs. 1.8%; P = 0.09), parainfluenza virus (PIV) 1 (5.1% vs. 2.8%; P = 0.2), or PIV4 (7.7% vs. 4.1%; P = 0.08), when children with multiple or sole virus detection were compared. Conversely, rhinovirus, adenovirus, enterovirus, bocavirus, PIV2, PIV3, metapneumovirus, coronavirus OC43, NL63, 229E were significantly more frequent among cases with multiple virus detection. Respiratory viruses were detected in over 90% of the cases, out of which 70% had multiple viruses. Several viruses are more commonly found in multiple virus detection whereas other viruses are similarly found in sole and in multiple virus detection. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Early rehabilitation and participation in focus - a Danish perspective on patients with severe acquired brain injury

    DEFF Research Database (Denmark)

    Smidt, Helle Rønn; Pallesen, Hanne; Buhl, Inge

    2016-01-01

    Early neurorehabilitation is an interdisciplinary field. Thus, in order to eliminate unnecessary barriers for individuals with severe acquired brain injury in early rehabilitation, we need rehabilitation science that supports both quantitative and qualitative research methods. Participation can b...

  19. Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?

    DEFF Research Database (Denmark)

    Gradel, Kim O; Jensen, Thøger G; Kolmos, Hans J

    2013-01-01

    We evaluated whether sepsis severity and C-reactive protein (CRP) level on admission prognostically corroborated or annulled each other in adult patients with incident community-acquired bacteremia (Funen, Denmark, 2000-2008). We used logistic regression and area under the receiver operating.......06), thus CRP contributed as much as sepsis severity to prognosis....

  20. Life goals and social identity in people with severe acquired brain injury: an interpretative phenomenological analysis.

    Science.gov (United States)

    Martin, Rachelle; Levack, William M M; Sinnott, K Anne

    2015-01-01

    While there is a growing body of literature exploring life goals in rehabilitation, little research has been undertaken that includes the voice of the end-user. This study examined the views and experiences of people with severe acquired brain injury regarding the place of "life goals" in residential rehabilitation. Interpretative phenomenological analysis was used to collect and analyze data from five semi-structured interviews with participants in a residential rehabilitation setting. Three inter-related themes emerged from this study. Social connectedness (being 'part of things') emerged as a life goal of central importance for all participants (Theme 1). However, in order to achieve this sense of belonging, the participants needed to tentatively balance the opportunities arising within their environmental milieu (Theme 2) with the interpersonal factors relating to their unchanged, changed and changing self-identity (Theme 3). This study suggests that social identity and social connectedness ought to be primary foci of rehabilitation rather than matters only of secondary concern. Consideration needs to be given to both the environmental contexts and the intrapersonal strategies that support people who require residential rehabilitation services to achieve social connection, and thus their life goals, following a severe acquired brain injury. Implications for Rehabilitation There is a need to better support people with severe acquired brain injury (ABI) in terms of their social relationships and social identity during the delivery of person-centered rehabilitation services. Within the clinical setting there should be regular, in depth and open dialogue in which the individuals' values and preferences are discovered. A focus on the coherence between daily activities and the person's life goals is required for people with severe ABI. Clinicians need to consider how life goals for individual people change or are re-prioritized over the life span.

  1. Severity assessment scores to guide empirical use of antibiotics in community acquired pneumonia.

    Science.gov (United States)

    Singanayagam, Aran; Chalmers, James D

    2013-10-01

    Severity assessment scores were first developed to predict the 30 day mortality in community acquired pneumonia; however, several guidelines have extended their use to guide empirical antibiotic prescription decisions. This approach has theoretical advantages because a decrease in broad-spectrum antibiotic treatment in low-risk patients might reduce antibiotic-related side-effects, and to give broad-spectrum therapy to patients at higher risk of death is intuitive. However, evidence in support of this approach is not clear. In particular, the British Thoracic Society guidelines suggest withholding a macrolide from patients with low CURB 65 scores, despite evidence that these patients have a higher frequency of atypical pathogens than do those with a higher severity of pneumonia. Severity scores do not perform well in some groups and might overestimate disease severity in elderly people, leading to inappropriate broad-spectrum treatment to those at high risk of complications such as Clostridium difficile infection. In this Review, we discuss the evidence for antibiotic prescribing guided by severity score and suggest that more evidence of effect and implementation is needed before this approach can be universally adopted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Acquired retinal pigmentary degeneration in a child with 13q deletion syndrome.

    Science.gov (United States)

    Aguilera, Zenia P; Belin, Peter J; Cavuoto, Kara M; Jayakar, Parul; McKeown, Craig A

    2015-10-01

    Orbeli syndrome, or 13q deletion syndrome, is a rare condition caused by a distal deletion in the long arm of chromosome 13. The syndrome is characterized by severe physical malformations and developmental delays and has been associated with numerous ocular manifestations. We report the case of a 10-year-old boy with 13q deletion syndrome, who was evaluated for impaired vision and found to have bilateral retinal pigmentary changes resembling those seen in retinitis pigmentosa. There has only been one other case of retinal pigment variation in association with 13q deletion syndrome; however, this represents the first case of bilateral symmetric retinal pigmentary changes with corresponding rod and cone dysfunction on electroretinography. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  3. Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia

    Science.gov (United States)

    Gattarello, Simone; Ramírez, Sergio; Almarales, José Rafael; Borgatta, Bárbara; Lagunes, Leonel; Encina, Belén; Rello, Jordi

    2015-01-01

    Objective To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. Methods A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. Results In the case of communityacquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions. Conclusion The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions. PMID:25909312

  4. Novel Therapeutic and Prophylactic Modalities to Protect the United States Armed Forces Against Mayor Biological Threat Agents

    Science.gov (United States)

    2007-08-01

    molecular weight forms of ADAMTS13 in plasma, suggesting its cleavage by proteases in addition to decreased synthesis in the liver.71 ADAMTS13... fulminate liver failure and death 101. In our experiments, PAI-1 is increased 2-fold in Sterne challenged mice (days 1-3) and 3-fold in ∆- Sterne...cells is affected by anthrax exposure is novel. AKT is also a regulator of glycogen synthesis via the phosphorylation of glycogen synthase kinase

  5. Social communication features in children following moderate to severe acquired brain injury: a cross-sectional pilot study.

    Science.gov (United States)

    Breau, Lynn M; Clark, Brenda; Scott, Ori; Wilkes, Courtney; Reynolds, Shawn; Ricci, Florencia; Sonnenberg, Lyn; Zwaigenbaum, Lonnie; Rashid, Marghalara; Goez, Helly R

    2015-04-01

    We compared the social communication deficits of children with moderate to severe acquired brain injury or autism spectrum disorder, while accounting for the role of attention-deficit hyperactivity disorder (ADHD) symptoms. Parents of 20 children aged 6 to 10 years (10 acquired brain injury; 10 autism spectrum disorder) completed the Social Communication Questionnaire, and Conners 3 Parent Short. A multivariate analysis of covariance revealed significant differences between groups in Social Communication Questionnaire restricted repetitive behavior scores, but not reciprocal social interaction or social communication. Multiple linear regressions indicated diagnosis did not predict reciprocal social interaction or social communication scores and that Conners 3 Parent Short Form hyperactivity scores were the strongest predictor of Social Communication Questionnaire reciprocal social interaction scores after accounting for age and Intelligence Quotient. The lack of difference in social communication deficits between groups may help in understanding the pathophysiology underlying the behavioral consequences of acquired brain injury. The link between hyperactivity and reciprocal interaction suggests that targeting hyperactivity may improve social outcomes in children following acquired brain injury. © The Author(s) 2014.

  6. TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B. [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Revetta, Frank [Department of Pathology, Vanderbilt University, Nashville, TN (United States); Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Department of Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States)

    2015-01-01

    The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. - Highlights: • Chemical inhibition of TGFβ signaling advances collective invasion

  7. Hydrocephalus is a rare outcome in community-acquired bacterial meningitis in adults

    DEFF Research Database (Denmark)

    Bodilsen, Jacob; Schønheyder, Henrik Carl; Nielsen, Henrik I

    2013-01-01

    BACKGROUND: Community-acquired bacterial meningitis (CABM) continues to have a high mortality rate and often results in severe sequelae among survivors. Lately, an increased effort has been focused on describing the neurological complications of meningitis including hydrocephalus. To aid in this ......BACKGROUND: Community-acquired bacterial meningitis (CABM) continues to have a high mortality rate and often results in severe sequelae among survivors. Lately, an increased effort has been focused on describing the neurological complications of meningitis including hydrocephalus. To aid...... in this field of research we set out to ascertain the risk and outcome of hydrocephalus in patients with community-acquired bacterial meningitis (CABM) in North Denmark Region. METHODS: We conducted a retrospective population-based cohort study of CABM cases above 14 years of age. Cases diagnosed during a 13......-year period, 1998 through 2010, were identified in a laboratory register and data were acquired through patient records. Cases not confirmed by culture met other strict inclusion criteria. The diagnosis of hydrocephalus relied upon the radiologists' reports on cranial imaging. Outcome was graded...

  8. Acquired Factor Xiii Deficiency: An Uncommon But Easily Missed Cause Of Severe Bleeding

    LENUS (Irish Health Repository)

    Fogarty, H

    2018-05-01

    Factor XIII (FXIII) is a plasma clotting protein involved in clot stabilization. Severe FXIII deficiency may present with severe, even fatal bleeding. Critically however, routine coagulation assays may be normal and only specific FXIII assays will detect the abnormality. Herein we discuss a case report of a patient with acquired FXIII deficiency in order to highlight the clinical challenges associated with establishing the diagnosis and discuss the treatment approach. A 70-year-old man presented with a gluteal haematoma despite no preceding personal history of bleeding. Extensive initial haemostatic investigations were normal until a specific FXIII assay showed a marked reduction in FXIII levels. With directed treatment, bleeding episodes ceased and remission was achieved. Clinical awareness of FXIII deficiency is important, so appropriate testing can be implemented in patients with unexplained bleeding diatheses, particularly those in whom bleeding responds poorly to standard replacement therapy.

  9. Severe Community-acquired Pneumonia Due to Legionella pneumophila Serogroup 6

    Directory of Open Access Journals (Sweden)

    Chung-Yu Chen

    2006-01-01

    Full Text Available Legionella pneumophila is a common cause of sporadic community-acquired pneumonia, but culture-proven legionellosis is rarely diagnosed. There is no laboratory test for Legionnaires' disease that can detect all patients with the disease. Culture is the standard diagnostic method and should be initiated as soon as possible in suspected cases. We describe a rare case of community-acquired pneumonia caused by L. pneumophila serogroup 6. A 77-year-old man was admitted to a tertiary care hospital because of high fever, productive cough, and progressive dyspnea. Chest radiography showed bilateral pneumonia, which led to respiratory failure necessitating mechanical ventilatory support. Despite antibiotic therapy, his condition continued to deteriorate and acute renal failure also developed. Urine was negative for L. pneumophila. Culture of the sputum yielded L. pneumophila serogroup 6, although there was no elevation of the serum antibody titer. Pneumonia resolved gradually and he was extubated after treatment with levofloxacin followed by erythromycin. L. pneumophila other than serogroup 1 should be included in the differential diagnosis of patients with suspected atypical community-acquired pneumonia.

  10. The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants

    DEFF Research Database (Denmark)

    He, Yi; Zheng, Qinlong; Jiang, Mengmeng

    2015-01-01

    contribution of ADAMTS-4 and ADAMTS-5 to cartilage degradation upon catabolic stimulation; ii) To investigate the effect of regulating the activities of key enzymes by mean of broad-spectrum inhibitors. Methods Bovine full-depth cartilage explants stimulated with tumor necrosis factor alpha (TNF...... protease for the generation of 374ARGS aggrecan fragment in the TNF-α/OSM stimulated bovine cartilage explants. This study addresses the need to determine the roles of ADAMTS-4 and ADAMTS-5 in human articular degradation in OA and hence identify the attractive target for slowing down human cartilage......Objective The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative...

  11. Acquired hyperostosis syndrome. Pt. 2

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W.; Hering, L.; Bargon, G.W.

    1988-12-01

    In the second part of this publication, we describe some additional findings in cases of sternocostoclavicular hyperostosis (SCCH). These include focal hyperostosis of the spine, in the pelvis and in the extremities and psoriatric skin lesions and severe forms of acne (acne conglobata, acne fulminans). An analysis of our 13 patients and of the relevant literature indicates that the hyperostosis is due to increased bone metabolism and heterotopic ossification of fibrous tissue and that these are the pathogenic bases of the changes in the axial skeleton, the pelvis and the bones of the extremities. We have suggested a scheme which would categorise the syndrom into complete, incomplete and possibly acquired forms. (orig./GDG).

  12. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

    Directory of Open Access Journals (Sweden)

    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  13. Increased expression of HIF-1α, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency

    Science.gov (United States)

    Misra, Sanjay; Shergill, Uday; Yang, Binxia; Janardhanan, Rajiv; Misra, Khamal D.

    2010-01-01

    Purpose A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. We tested the hypothesis that there is increased gene expression of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor- A (VEGF-A) and its receptors (VEGFR-1, -2), matrix metalloproteinase-2 (MMP-2), -9 (MMP-9), tissue inhibitor of metalloproteinase-1, -2 (TIMP-1, -2), and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. Materials and methods Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal insufficiency and characterized in eight mice. Twenty eight days later, an AVF (n=11) was created from the right carotid artery to ipsilateral jugular vein and the mice were sacrificed at day 7 (n=4) and day 14 (n=4). The outflow and control veins were removed for gene expression. Three mice were sacrificed at day 28 for histologic analysis. Results The mean serum blood urea nitrogen remained significantly elevated for 8 weeks when compared to baseline (P<0.05). By day 7, there was a significant increase in the expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with HIF-1α and TIMP-1 being significantly elevated at day 14 (P<0.05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. Conclusions A mouse model of renal insufficiency with AVF was developed which had increased expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28. PMID:20598569

  14. Increased expression of HIF-1alpha, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency.

    Science.gov (United States)

    Misra, Sanjay; Shergill, Uday; Yang, Binxia; Janardhanan, Rajiv; Misra, Khamal D

    2010-08-01

    A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. The authors tested the hypothesis that there is increased gene expression of hypoxia-inducible factor-1 alpha (HIF-1alpha); vascular endothelial growth factor-A (VEGF-A) and its receptors (VEGFR-1, -2); matrix metalloproteinase-2 (MMP-2), -9 (MMP-9); tissue inhibitor of metalloproteinase-1, -2 (TIMP-1, -2); and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal function characterized in eight animals. Twenty eight days later, an AVF (n = 11) was created from the right carotid artery to ipsilateral jugular vein, and the mice were killed at day 7 (n = 4) and day 14 (n = 4). The outflow and control veins were removed for gene expression. Three mice were killed at day 28 for histologic analysis. The mean serum blood urea nitrogen level remained significantly elevated for 8 weeks when compared with baseline (P < .05). By day seven, there was a significant increase in the expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein, with HIF-1alpha and TIMP-1 levels significantly elevated at day 14 (P < .05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. A mouse model of renal insufficiency with AVF was developed that had increased expression of HIF-1alpha, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28. Copyright (c) 2010 SIR. Published by Elsevier Inc. All rights reserved.

  15. Usefulness of Plasma YKL-40 in Management of Community-Acquired Pneumonia Severity in Patients

    Directory of Open Access Journals (Sweden)

    Hsiang-Ling Wang

    2013-11-01

    Full Text Available Plasma YKL-40 level has been reported as playing a significant role in community-acquired pneumonia (CAP. However, the correlation between plasma level of YKL-40 and the severity of CAP has not been reported. This study identifies the relationship between plasma level changes of the YKL-40 gene in adult patients hospitalized with CAP. The ELISA was used to measure the plasma YKL-40 level from 61 adult CAP patients before and after antibiotic treatment and from 60 healthy controls. The plasma YKL-40 levels were significantly increased in patients with CAP compared to normal controls. Moreover, the plasma concentration of YKL-40 correlated with the severity of CAP based on the pneumonia severity index (PSI score (r = 0.630, p < 0.001, the CURB-65 (confusion, uremia, respiratory rate, BP, age 65 years score (r = 0.640, p < 0.001, the Acute Physiology And Chronic Health Evaluation II (APACHE II score (r = 0.539, p < 0.001 and length of hospital stay (r = 0.321, p = 0.011, respectively. In conclusion, plasma YKL-40 may play a role in the diagnosis and clinical assessment of CAP severity, which could potentially guide the development of treatment strategies.

  16. The acquired hyperostosis syndrome. Pt. 2

    International Nuclear Information System (INIS)

    Dihlmann, W.; Hering, L.; Bargon, G.W.

    1988-01-01

    In the second part of this publication, we describe some additional findings in cases of sternocostoclavicular hyperostosis (SCCH). These include focal hyperostosis of the spine, in the pelvis and in the extremities and psoriatric skin lesions and severe forms of acne (acne conglobata, acne fulminans). An analysis of our 13 patients and of the relevant literature indicates that the hyperostosis is due to increased bone metabolism and heterotopic ossification of fibrous tissue and that these are the pathogenic bases of the changes in the axial skeleton, the pelvis and the bones of the extremities. We have suggested a scheme which would categorise the syndrom into complete, incomplete and possibly acquired forms. (orig./GDG) [de

  17. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview

    Directory of Open Access Journals (Sweden)

    Soichi Takeda

    2016-05-01

    Full Text Available A disintegrin and metalloproteinase (ADAM family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the “ADAM_CR” domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates.

  18. 26 CFR 1.9002-6 - Acquiring corporation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5(d) of the... corporation by another corporation in a distribution or transfer described in section 381(a) of the Code the...

  19. Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity.

    Science.gov (United States)

    Muravlyova, Larissa; Molotov-Luchankiy, Vilen; Bakirova, Ryszhan; Klyuyev, Dmitriy; Demidchik, Ludmila; Lee, Valentina

    2016-03-15

    At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. To sum up, our derived data show, that injury of erythrocytes' redox-status and blood plasma components plays an essential role in development and progression CAP.

  20. Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

    Science.gov (United States)

    Mörtzell, M; Berlin, G; Nilsson, T; Axelsson, C G; Efvergren, M; Audzijoni, J; Griskevicius, A; Ptak, J; Blaha, M; Tomsova, H; Liumbruno, G M; Centoni, P; Newman, E; Eloot, S; Dhondt, A; Tomaz, J; Witt, V; Rock, G; Stegmayr, B

    2011-10-01

    Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact

  1. Endogenous carboxyhemoglobin concentrations in the assessment of severity in patients with community-acquired pneumonia.

    Science.gov (United States)

    Corbacioglu, Seref Kerem; Kilicaslan, Isa; Bildik, Fikret; Guleryuz, Atacan; Bekgoz, Burak; Ozel, Ayca; Keles, Ayfer; Demircan, Ahmet

    2013-03-01

    Previous studies have shown that carbon monoxide, which is endogenously produced, is increased in community-acquired pneumonia (CAP). However, it has not been studied enough whether severity of pneumonia is correlated with increased carboxyhemoglobin (COHb) concentrations in CAP. The aim of this study was to determine whether endogenous carbon monoxide levels in patients with CAP were higher compared with the control group and, if so, to determine whether COHb concentrations could predict severity in CAP. Eighty-two patients with CAP were evaluated in this cross-sectional study during a 10-month period. Demographic data, pneumonia severity index and confusion, uremia, rate respiratory, pressure blood, age>65 (CURB-65) scores, hospital admission or discharge decisions, and 30-day hospital mortality rate were recorded. In addition, 83 control subjects were included to study. The COHb concentration was measured in arterial blood sample. The levels of COHb in patients with CAP were 1.70% (minimum-maximum, 0.8-3.2), whereas those in control subjects, 1.40% (minimum-maximum, 0.8-2.9). The higher COHb concentrations in patients with CAP were statistically significant (P < .05). Concentration of COHb correlated with pneumonia severity index (P = .04, r = 0.187); however, it did not correlate with CURB-65 (P = .218, r = 0.112). Although COHb concentrations show an increase in patients with pneumonia, it was concluded that this increase did not act as an indicator in diagnosis process or prediction of clinical severity for the physicians. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity,

    Directory of Open Access Journals (Sweden)

    Vojislav Cupurdija

    2015-02-01

    Full Text Available Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP, correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65 scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively. The major cost drivers, in descending order, were the opportunity cost (lost productivity; diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe.

  3. Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia

    Directory of Open Access Journals (Sweden)

    Kok-Khun Yong

    2016-01-01

    Full Text Available Monocyte chemoattractant protein (MCP-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP. However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II; confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65; and pneumonia severity index (PSI scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs and neutrophils as well as the level of C-reactive protein (CRP and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001, CURB-65 (r = 0.468, p < 0.001, and APACHE II (r = 0.360, p < 0.001 scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

  4. Effects of baseline and early acquired thrombocytopaenia on long-term mortality in patients undergoing percutaneous coronary intervention with bivalirudin.

    Science.gov (United States)

    Ali, Ziad A; Qureshi, Yasir H; Karimi Galougahi, Keyvan; Poludasu, Shyam; Roye, Swathi; Krishnan, Prakash; Zalewski, Adrian; Shah, Zainab Z; Bhatti, Navdeep; Kalapatapu, Kumar; Mehran, Roxana; Dangas, George; Kini, Annapoorna S; Sharma, Samin K

    2016-04-08

    Bivalirudin use as a procedural anticoagulant in patients undergoing percutaneous coronary intervention (PCI) is associated with a lower incidence of thrombocytopaenia compared to other antithrombotic agents. We aimed to evaluate the prognostic impact of baseline thrombocytopaenia and early changes in platelet counts among patients undergoing PCI with exclusive use of bivalirudin. We evaluated 7,505 patients who underwent PCI over a period of eight years. Patients who received unfractionated heparin and glycoprotein IIb/IIIa receptor inhibitors were specifically excluded. Eight hundred and fifty-eight (11.4%) patients had baseline thrombocytopaenia and 451 (6.0%) developed acquired thrombocytopaenia. After adjustment for potential covariates, moderate to severe acquired thrombocytopaenia was the strongest independent predictor (HR 4.34, 95% CI: 2.13-8.84; pevents, which included major adverse cardiac events and major bleeding complications. Age, male gender, baseline platelet count and intra-aortic balloon pump (IABP) insertion were independent predictors of in-hospital acquired thrombocytopaenia. After a mean follow-up of 2.6±1.7 years, moderate to severe baseline thrombocytopaenia (HR 2.42, 95% CI: 1.79-3.29; p67 k) were significant predictors of mortality. In patients undergoing PCI with bivalirudin, moderate to severe baseline and acquired thrombocytopaenia along with severe changes in platelet count are associated with higher long-term mortality.

  5. Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

    Science.gov (United States)

    Asai, Nobuhiro; Motojima, Shinji; Ohkuni, Yoshihiro; Matsunuma, Ryo; Nakasima, Kei; Iwasaki, Takuya; Nakashita, Tamao; Otsuka, Yoshihito; Kaneko, Norihiro

    2012-06-11

    Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP. A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients' characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups. Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group. Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to

  6. Using data-driven rules to predict mortality in severe community acquired pneumonia.

    Directory of Open Access Journals (Sweden)

    Chuang Wu

    Full Text Available Prediction of patient-centered outcomes in hospitals is useful for performance benchmarking, resource allocation, and guidance regarding active treatment and withdrawal of care. Yet, their use by clinicians is limited by the complexity of available tools and amount of data required. We propose to use Disjunctive Normal Forms as a novel approach to predict hospital and 90-day mortality from instance-based patient data, comprising demographic, genetic, and physiologic information in a large cohort of patients admitted with severe community acquired pneumonia. We develop two algorithms to efficiently learn Disjunctive Normal Forms, which yield easy-to-interpret rules that explicitly map data to the outcome of interest. Disjunctive Normal Forms achieve higher prediction performance quality compared to a set of state-of-the-art machine learning models, and unveils insights unavailable with standard methods. Disjunctive Normal Forms constitute an intuitive set of prediction rules that could be easily implemented to predict outcomes and guide criteria-based clinical decision making and clinical trial execution, and thus of greater practical usefulness than currently available prediction tools. The Java implementation of the tool JavaDNF will be publicly available.

  7. 13 CFR 107.880 - Assets acquired in liquidation of Portfolio securities.

    Science.gov (United States)

    2010-01-01

    ... SMALL BUSINESS INVESTMENT COMPANIES Financing of Small Businesses by Licensees Structuring Licensee's Financing of An Eligible Small Business: Terms and Conditions of Financing § 107.880 Assets acquired in... Financing(s) to the Small Business must not exceed your overline limit under § 107.740; and (2) Your total...

  8. Isolated acquired factor VII deficiency: review of the literature.

    Science.gov (United States)

    Mulliez, Sylvie M N; Devreese, Katrien M J

    2016-04-01

    Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

  9. Dynamics of Severe and Non-Severe Invasive Pneumococcal Disease in Young Children in Israel Following PCV7/PCV13 Introduction.

    Science.gov (United States)

    Glikman, Daniel; Dagan, Ron; Barkai, Galia; Averbuch, Diana; Guri, Alex; Givon-Lavi, Noga; Ben-Shimol, Shalom

    2018-05-10

    The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on non-severe IPD (mostly occult bacteremia) has not yet been fully elucidated.We assessed severe and non-severe IPD (SIPD and NSIPD, respectively) rate dynamics in children <5 years in Israel before and after PCV7/PCV13 implementation. A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015, were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not-hospitalized or hospitalized in a non-intensive care unit <5 days, without mortality). Three sub-periods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated. Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified.In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined non-significantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR=0.4; 0.32-0.51) and 64% (IRR=0.36; 0.32-0.42), respectively. Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the two groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

  10. Self-esteem as a predictor of psychological distress after severe acquired brain injury: an exploratory study.

    Science.gov (United States)

    Cooper-Evans, Samantha; Alderman, Nick; Knight, Caroline; Oddy, Michael

    2008-01-01

    This study explored the effects of severe acquired brain injury (ABI) on self-esteem. A within-subjects design investigated 22 severe ABI survivors' self-reported responses on measures of self-esteem, mood and awareness of deficit. Data on cognitive ability and awareness of degree of executive impairment were included in the analysis. Self-esteem was measured using Rosenberg's Self-Esteem Scale (Rosenberg) and psychological distress by the Hospital Anxiety and Depression Scale (HADS). Self-esteem was found to be consistent over a two-week interval. Participants reported that their self-esteem had suffered following ABI when contrasting their current self-esteem with their retrospective perceptions. Self-esteem was highly correlated with psychological distress. More intact cognitive functioning and awareness of deficit were associated with lower self-esteem. The paradoxical finding that survivors who were more impaired cognitively and/or less aware of their deficits reported higher self-esteem poses an ethical dilemma for clinicians. It is hoped that this finding, along with the consistency of self-esteem ratings sparks further debate about how best to address issues of self-esteem among severe ABI survivors, particularly in the context of psychological distress, during rehabilitation.

  11. Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Adrian Ceccato

    Full Text Available Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial.We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone and corticosteroid arm (placebo or corticosteroids. The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure.The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374; however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31% vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24% vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0% vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009. We found

  12. Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

    Directory of Open Access Journals (Sweden)

    Asai Nobuhiro

    2012-06-01

    Full Text Available Abstract Background Non-HIV Pneumocystis pneumonia (PCP can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS, the CURB-65 score of the British Respiratory Society (BTS and the Pneumonia Severity Index (PSI of the Infectious Diseases Society of America (IDSA are widely used in patients with community-acquired pneumonia (CAP in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP. Methods A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR for respiratory samples with chest x-ray and computed tomography (CT findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups. Results Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%, and 7/15 (46.7% died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%, and 8 of the 16 (50% died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100% developed respiratory failure and 8/14 (57.1% died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group. Conclusions Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay

  13. Association of the position of a hospital-acquired condition diagnosis code with changes in medicare severity diagnosis-related group assignment.

    Science.gov (United States)

    Johnson, Tricia; Kane, Jason M; Odwazny, Richard; McNutt, Robert

    2014-11-01

    Incentives to improve quality include paying less for adverse events, including the Centers for Medicare and Medicaid Services' policy to not pay additionally for events classified as hospital-acquired conditions (HACs). This policy is controversial, as variable coding practices at hospitals may lead to differences in the inclusion and position of HACs in the list of codes used for Medicare Severity Diagnosis-Related Group (MS-DRG) assignment. Evaluate changes in MS-DRG assignment for patients with an HAC and test the association of the position of an HAC in the list of International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes with change in MS-DRG assignment. Retrospective analysis of patients discharged from hospital members of the University HealthSystem Consortium's Clinical Data Base between October 2007 and April 2008. Comparisons were made between the MS-DRG assigned when the HAC was not included in the list of ICD-9 diagnosis codes and the MS-DRG that would have been assigned had the HAC code been included in the assignment. Of the 7027 patients with an HAC, 13.8% changed MS-DRG assignment when the HAC was removed. An HAC in the second position versus third position or lower was associated with a 40-fold increase in the likelihood of MS-DRG change. The position of an HAC in the list of diagnosis codes, rather than the presence of an HAC, is associated with a change in MS-DRG assignment. HACs have little effect on reimbursement unless the HAC is in the second position and patients have minor severity of illness. © 2014 Society of Hospital Medicine.

  14. Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

    Science.gov (United States)

    Girard, Timothy D; Self, Wesley H; Edwards, Kathryn M; Grijalva, Carlos G; Zhu, Yuwei; Williams, Derek J; Jain, Seema; Jackson, James C

    2018-06-01

    Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

  15. Intravenous saline administration in patients with severe acquired brain injury and orthostatic intolerance for tilt-table mobilization

    DEFF Research Database (Denmark)

    Riberholt, Christian; Olesen, Niels; Hovind, Peter

    2018-01-01

    Primary objective: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin–angiotensin–aldosterone system before and after HUT in patients with severe acquired brain injury (ABI). Research...... artery blood flow velocity. Blood samples were collected before and after two HUT sessions separated by 1 hour and saline was administered in between. Main outcomes and results: Patients’ ability to stand upright did not change after saline administration due to OH. The patients showed signs of reduced...... fluid administration. Research focusing on the ability to retain fluid after bed rest is warranted....

  16. Acquired ventricular septal defect due to infective endocarditis

    Directory of Open Access Journals (Sweden)

    Randi E Durden

    2018-01-01

    Full Text Available Acquired intracardiac left-to-right shunts are rare occurrences. Chest trauma and myocardial infection are well-known causes of acquired ventricular septal defect (VSD. There have been several case reports describing left ventricle to right atrium shunt after infective endocarditis (IE. We present here a patient found to have an acquired VSD secondary to IE of the aortic and tricuspid valves in the setting of a known bicuspid aortic valve. This is the first case reported of acquired VSD in a pediatric patient in the setting of IE along with literature review of acquired left-to-right shunts.

  17. An extra X does not prevent acquired hemophilia - Pregnancy-associated acquired hemophilia A.

    Science.gov (United States)

    Barg, Assaf A; Livnat, Tami; Kenet, Gili

    2017-03-01

    Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). With an estimated annual incidence of 1.3 to 1.5 per million, AHA is a rare disease. An extremely rare form of AHA has been described among women in the peripartum period, and may present with peripartum hemorrhage. Notably, although hemorrhagic symptoms commonly present 1-4 months around delivery, they may occur up to 1 year after parturition. When caring for a mother with AHA it is important to note that Factor VIII inhibitor may be transferred via the placenta from the mother to the fetus. Hence the newborn may also be affected. It is important to increase the awareness of Gynecologists for clinical symptoms and laboratory signs of AHA in order to avoid delayed diagnosis. Treatment may involve use of bypass agents to control hemorrhage, despite the risk of thrombosis, while immunomodulation (with increasing role for Rituximab) may be required to eradicate the inhibiting antibodies. Our review will evaluate the epidemiology, diagnosis, clinical course and treatment of peripartum AHA, focusing upon mother and infant care. © 2017 Elsevier Ltd. All rights reserved.

  18. Challenges in dengue fever in the elderly: atypical presentation and risk of severe dengue and hospital-acquired infection [corrected].

    Directory of Open Access Journals (Sweden)

    Emily K Rowe

    2014-04-01

    Full Text Available BACKGROUND/METHODS: To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO dengue classification and outcomes between adult (<60 and elderly (≥60 dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included. RESULTS: Of the 6989 cases, 295 (4.4% were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF (29.2% vs. 21.4% and severe dengue (SD (20.3% vs. 14.6% (p<0.05. Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4% (p = 0.014, but not WHO 2009 probable dengue (75.3% vs. 71.5%. Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006 and malaise/lethargy (p = 0.033 while the adults had significantly more mucosal bleeding (p<0.001. Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days, and suffered more pneumonia (3.8% vs. 0.7% and urinary infection (1.9% vs. 0.3% (p = 0.003. Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37-2.88, critical illness (aOR 5.13, 95%CI 2.59-9.75, HAI (aOR 12.06, 95%CI 7.39-19.9, Charlson score (aOR 6.9, 95%CI 2.02-22.56 and severe dengue (DHF/dengue shock syndrome/SD (aOR 2.24, 95%CI 1.83-2.74. CONCLUSION: Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside from dengue

  19. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

    Science.gov (United States)

    Knoebl, P; Marco, P; Baudo, F; Collins, P; Huth-Kühne, A; Nemes, L; Pellegrini, F; Tengborn, L; Lévesque, H

    2012-04-01

    Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA. © 2012 International Society on Thrombosis and Haemostasis.

  20. Corpus callosum demyelination associated with acquired stuttering.

    Science.gov (United States)

    Decker, Barbara McElwee; Guitar, Barry; Solomon, Andrew

    2018-04-21

    Compared with developmental stuttering, adult onset acquired stuttering is rare. However, several case reports describe acquired stuttering and an association with callosal pathology. Interestingly, these cases share a neuroanatomical localisation also demonstrated in developmental stuttering. We present a case of adult onset acquired stuttering associated with inflammatory demyelination within the corpus callosum. This patient's disfluency improved after the initiation of immunomodulatory therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. p13 from group II baculoviruses is a killing-associated gene

    Directory of Open Access Journals (Sweden)

    Yipeng Qi

    2012-12-01

    Full Text Available p13 gene was first described in Leucania separata multinuclearpolyhedrosis virus (Ls-p13 several years ago, but the functionof P13 protein has not been experimentally investigated todate. In this article, we indicated that the expression of p13from Heliothis armigera single nucleocapsid nucleopolyhedrovirus(Ha-p13 was regulated by both early and late promoter.Luciferase assay demonstrated that the activity of Ha-p13promoter with hr4 enhancer was more than 100 times inheterologous Sf9 cells than that in nature host Hz-AM1 cells.Both Ls-P13 and Ha-P13 are transmembrane proteins. Confocalmicroscopic analysis showed that both mainly located in thecytoplasm membrane at 48 h. Results of RNA interferenceindicated that Ha-p13 was a killing-associated gene for hostinsects H. armigera. The AcMNPV acquired the mentionedkilling activity and markedly accelerate the killing rate whenexpressing Ls-p13. In conclusion, p13 is a killing associatedgene in both homologous and heterologous nucleopolyhedrovirus.

  2. Disease: H00225 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ID:18574040 ... AUTHORS ... Sadler JE ... TITLE ... Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopen...MID:17124092 ... AUTHORS ... Sadler JE ... TITLE ... Thrombotic thrombocytopenic purpura: a moving target. ... JOURN

  3. The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections.

    Science.gov (United States)

    van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Frencken, Jos F; Scicluna, Brendon P; Klein Klouwenberg, Peter M C; Zwinderman, Aeilko H; Lutter, Rene; Horn, Janneke; Schultz, Marcus J; Bonten, Marc M J; Cremer, Olaf L; van der Poll, Tom

    2017-08-15

    Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses. To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not. Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication. Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications. Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.

  4. Management of Acquired Atresia of the External Auditory Canal.

    Science.gov (United States)

    Bajin, Münir Demir; Yılmaz, Taner; Günaydın, Rıza Önder; Kuşçu, Oğuz; Sözen, Tevfik; Jafarov, Shamkal

    2015-08-01

    The aim was to evaluate surgical techniques and their relationship to postoperative success rate and hearing outcomes in acquired atresia of the external auditory canal. In this article, 24 patients with acquired atresia of the external auditory canal were retrospectively evaluated regarding their canal status, hearing, and postoperative success. Acquired stenosis occurs more commonly in males with a male: female ratio of 2-3:1; it seems to be a disorder affecting young adults. Previous ear surgery (13 patients, 54.2%) and external ear trauma (11 patients, 45.8%) were the main etiological factors of acquired ear canal stenosis. Mastoidectomy (12/13) and traffic accidents (8/11) comprise the majority of these etiological factors. Endaural incision is performed in 79.2% and postauricular incision for 20.8% of cases during the operation. As types of surgical approach, transcanal (70.8%), transmastoid (20.8%), and combined (8.4%) approaches are chosen. The atretic plate is generally located at the bony-cartilaginous junction (37.5%) and in the cartilaginous canal (33.3%); the bony canal is involved in a few cases only. Preserved healthy canal skin, split- or full-thickness skin grafts, or pre- or postauricular skin flaps are used to line the ear canal, but preserved healthy canal skin is preferred. The results of surgery are generally satisfactory, and complications are few if surgical principles are followed.

  5. Clinical Predictors of Hospital-acquired Pneumonia Associated with Acute Ischemic

    Directory of Open Access Journals (Sweden)

    Alexis Suárez Quesada

    2015-06-01

    Full Text Available Background: hospital-acquired pneumonia is a constant challenge given the current microbiological spectrum, antimicrobial resistance together with its high mortality, morbidity and hospital costs. Objective: to identify the clinical predictors of pneumonia associated with acute ischemic stroke. Methods: a prospective cohort study was conducted in 201 patients diagnosed with acute ischemic stroke consecutively admitted to the stroke unit of the General Carlos Manuel de Céspedes Teaching Hospital during the first seven days after the onset, from January 2012 through December 2013. The independent predictors of hospital-acquired pneumonia were obtained using multivariable logistic regression. Results: fifty six point seven percent were male. The mean age was 64.17 ± 14.33 years. Cases of hospital-acquired pneumonia associated with stroke accounted for 19, 9 %. Subjects who developed pneumonia were older (68.55 ± 13.51 vs. 63.08 ± 14.36 years, had a lower score in the Glasgow Coma Scale (8.00 ± 2.60 vs. 14.00 ± 2.82, and an increased number of leukocytes at admission (10.888 ± 3.487 vs. 9.233 ± 2.539 × 109/L. The following independent factors were identified: Glasgow Coma Scale ≤ 11 (OR: 26.099; 95 % CI 7.164-85.075, history of chronic obstructive pulmonary disease (OR: 8.896; 95 % CI 1.203-65.779, dysphagia (OR: 7.652; 95 % CI 2.369- 24.720, history of heart failure (OR: 4.583; 95 % CI 1.240- 16.932 and dysarthria/severe motor aphasia (OR: 4.222; 95 % CI 1.374- 12.975. Conclusions: the resulting logistic regression model is valid for predicting post-stroke pneumonia based on data routinely acquired.

  6. Severe community-acquired pneumonia caused by Mycoplasma pneumoniae in young female patient

    Directory of Open Access Journals (Sweden)

    Milačić Nena

    2015-07-01

    Full Text Available Mycoplasma pneumonia is common agent causing community acquired pneumonia in younger population. However, the course of illness is usually benign and is rarely associated with pulmonary complications. We report a 27 years old female patient with unilateral pneumonia followed by pleural effusion and adhesions on the same side. This potential source of infection should be considered in young patients where resolution of symptoms from pneumonia is delayed.

  7. A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults)

    NARCIS (Netherlands)

    Patterson, Scott; Webber, Chris; Patton, Michael; Drews, Wayne; Huijts, Susanne M.; Bolkenbaas, Marieke; Gruber, William C.; Scott, Daniel A.; Bonten, Marc J M

    2016-01-01

    Background: The Community Acquired Pneumonia immunization Trial in Adults (CAPiTA) was conducted to evaluate 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) in adults

  8. Diagnosis and Treatment of Community-Acquired Pneumonia in Children

    Directory of Open Access Journals (Sweden)

    I.A. Karymdzhanov

    2016-02-01

    The initial antibiotic therapy of community-acquired pneumonia is carried out empirically. In the treatment of severe community-acquired pneumonia in children from 2 months to 5 years, the drug of choice is amoxicillin orally. Macrolides are the drugs of choice for children aged 5 to 16 years. In severe pneumonia, drugs of choice are amoxicillin clavulanate, 2nd–4th generation cephalosporins. In general, the duration of antibiotic therapy in the community-acquired pneumonia caused by typical bacteria is 7–10 days, by atypical bacteria — 10–14 days. In the real clinical practice, the errors associated with the choice of drug, route of administration, dosage, regimen of application, length of treatment are frequent during antibacterial therapy.

  9. Investigating the Acquisition, Generalization, and Emergence of Untrained Verbal Operants for Mands Acquired Using the Picture Exchange Communication System in Adults with Severe Developmental Disabilities

    Science.gov (United States)

    Ziomek, M. M.; Rehfeldt, R. A.

    2008-01-01

    This study compared the total amount of training time and total number of trial blocks for individuals with severe developmental disabilities to acquire mands under control of unconditioned establishing operations and mands under control of transitive conditioned establishing operations for manual sign and for the Picture Exchange Communication…

  10. Non-ST Elevation Myocardial Infarction and Severe Peripheral Artery Disease in a 20-Year-Old with Perinatally Acquired Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    Purva Sharma

    2018-01-01

    Full Text Available Human immunodeficiency virus (HIV infection confers an increased risk of cardiovascular disease, including acute coronary syndrome (ACS. Patients with perinatally acquired HIV may be at increased risk due to the viral infection itself and exposure to HAART in utero or as part of treatment. A 20-year-old female with transplacentally acquired HIV infection presented with symptoms of transient aphasia, headache, palpitations, and blurry vision. She was admitted for hypertensive emergency with blood pressure 203/100 mmHg. Within a few hours, she complained of typical chest pain, and ECG showed marked ST depression. Troponin I levels escalated from 0.115 to 10.8. She underwent coronary angiogram showing 95% stenosis of the right coronary artery (RCA and severe peripheral arterial disease including total occlusion of both common iliacs and 95% infrarenal aortic stenosis with collateral circulation. She underwent successful percutaneous intervention with a drug-eluting stent to the mid-RCA. Patients with HIV are at increased risk for cardiovascular disease. Of these, coronary artery disease is one of the most critical complications of HIV. Perinatally acquired HIV infection can be a high-risk factor for cardiovascular disease. A high degree of suspicion is warranted in such patients, especially if they are noncompliant to their ART.

  11. Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

    Directory of Open Access Journals (Sweden)

    Starla Hayward

    2016-04-01

    Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.

  12. Zakrzepowa plamica małopłytkowa – diagnostyka i leczenie

    Directory of Open Access Journals (Sweden)

    Jolanta Korsak

    2013-12-01

    Full Text Available Zakrzepowa plamica małopłytkowa (thrombotic thrombocytopenic purpura, TTP początkowo charakteryzowała się pentadą objawów: małopłytkowością, niedokrwistością hemolityczną mikroangiopatyczną, zaburzeniami układu nerwowego, niewydolnością nerek i gorączką. Jednak u 35% chorych z rozpoznaniem TTP nie stwierdza się wszyst‑ kich tych dolegliwości: nie występują u nich objawy neurologiczne, zaburzenia funkcji nerek oraz gorączka. Obec‑ nie zakrzepową plamicę małopłytkową rozpoznaje się na podstawie małopłytkowości i niedokrwistości mikroangiopatycznej. Diagnostyka obejmuje badanie morfologiczne krwi obwodowej wraz z rozmazem, badanie czynności nerek i oznaczenie aktywności LDH. Pomocne w rozpoznaniu jest oznaczenie aktywności metaloprote‑ azy ADAMTS13 i miana przeciwciał anty-ADAMTS13. W terapii w pierwszym rzucie stosuje się plazmaferezę lecz‑ niczą – powinna ona zostać przeprowadzona nawet wtedy, gdy diagnoza jest niepewna. Plazmafereza usuwa mul‑ timery ULvWF i nabyte przeciwciała skierowane przeciw ADAMTS13. Przetoczenie osocza nie jest tak efektywne jak plazmafereza, lecz może być stosowane tymczasowo. Efekt leczenia oceniany jest na podstawie unormowa‑ nia się aktywności LDH oraz ustąpienia małopłytkowości, niedokrwistości i zmian neurologicznych. Inną możli‑ wością terapeutyczną jest podawanie glikokortykosteroidów oraz immunoglobulin. U niektórych chorych korzystne może być wykonanie splenektomii. Ostatnio stosuje się także rytuksymab – powoduje on redukcję miana inhibitora ADAMTS13 i wzrost aktywności enzymu. Po leczeniu rytuksymabem odnotowano remisje kliniczne w przypad‑ kach, w których zawiodły inne metody terapii.

  13. Severe virus associated community acquired pneumonia: predictors of lethality

    Directory of Open Access Journals (Sweden)

    T. O. Pertseva

    2016-06-01

    Full Text Available Despite the fact that the influenza virus pathogenicity factors have been well studied in vitro, in vivo lack is presented in understanding of the those risk factors, objective and laboratory parameters, which related most of all to the fatal virus-associated community-aquired pneumonia (CAP. That is why the purpose of the study was to study the clinical and laboratory characteristics of patients with severe virus-associated CAP during the 2015–2016 influenza epidemic and their role as predictors of patients’ mortality. To do this, patients with severe virus-associated CAP were examined. They were divided into 2 groups depending on the outcome of treatment: 1st- deaths from the virus-associated severe CAP and 2nd - patients with successful treatment of the severe virus-associated CAP. Special statistical method was used – one-dimensional analysis of variance to compare individual parameters between the two groups of patients (surviving and deceased. Pearson χ2 test (contingency table was used for categorical variables. Factors that were significant predictors of mortality as a result of univariate analysis were tested using multifactorial analysis using logistic regression. In the final model, each parameter must have had a significant impact on mortality. It was found that risk factors for death in patients with severe virus-associated CAP according to univariate analysis were: presence of obesity, disorders of consciousness, BH≥35 min, SaO2<80%, PaO2<50 mm Hg, mmHg PaCO2 ≥50 mmHg during hospitalization. Independent predictors of mortality according to the logistic regression are the presence of obesity, disorders of consciousness, PaO2<50 mm Hg, mmHg PaCO2 ≥50 mmHg. Given that among clinical and laboratory parameters key parameters that significantly influence the outcome, are indicators of the severity of hypoxia and hypoxemia, a major step in determining the severity of the patients with virus-associated severe emergency is

  14. Epidemiological Study of Hospital-Acquired Bacterial Conjunctivitis in a Level III Neonatal Unit

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    Catarina Dias

    2013-01-01

    Full Text Available Background. Conjunctivitis is one of the most frequently occurring hospital-acquired infections among neonates, although it is less studied than potentially life-threatening infections, such as sepsis and pneumonia. Objectives. The aims of our work were to identify epidemiologic characteristics, pathogens, and susceptibility patterns of bacterial hospital-acquired conjunctivitis (HAC in a level III neonatal unit. Materials and Methods. Data were collected retrospectively from patient charts and laboratory databases. Hospital-acquired conjunctivitis was defined in accordance with the Centers for Disease Control/National Healthcare Safety Network (CDC/NHSN diagnostic criteria. Results. One or more episodes of HAC were diagnosed in 4,0% ( of 1492 neonates admitted during the study period. Most of the episodes involved premature (75,4% and low birth weight (75,4% neonates. Infection rates were higher among patients undergoing noninvasive mechanical ventilation (46,7%, parenteral nutrition (13,6%, and phototherapy (6,8%. Predominant pathogens included Serratia marcescens (27,9%, Escherichia coli (23%, and Pseudomonas aeruginosa (18%. Susceptibility patterns revealed bacterial resistances to several antibiotic classes. Gentamicin remains the adequate choice for empirical treatment of HAC in our NICU. Conclusion. It is important to know the local patterns of the disease in order to adjust prevention strategies. Our work contributes to the epidemiological characterization of a sometimes overlooked disease.

  15. An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.

    Directory of Open Access Journals (Sweden)

    Simone Accordini

    Full Text Available Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD study (www.geird.org, 326 subjects (aged 20-64 with ever asthma were identified from the general population in Verona (Italy between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes was analysed. A symptom and treatment score (STS and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR. SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4 was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04, whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2 = 0.94 in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09. Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1 or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever

  16. [Validation of the Pneumonia Severity Index for hospitalizing patients with community-acquired pneumonia].

    Science.gov (United States)

    Querol-Ribelles, José M; Tenías, José M; Querol-Borrás, José M; González-Granda, Damiana; Hernández, Manuel; Ferreruela, Rosa; Martínez, Isidoro

    2004-04-10

    Our main objective was to assess the utility of the Pneumonia Severity Index (PSI) to decide the site of care home or hospital of patients with community-acquired pneumonia (CAP). All CAP patients who came to the emergency department from 1 January to 31 December, 2000, were prospectively assessed with a protocol based on the PSI and additional admission criteria applied to classes I, II and III. Mortality within 30 days and poor outcome were used as endpoints. We tested the diagnostic efficacy of the PSI scale in predicting mortality or unfavourable events by calculating the area below the ROC curve. Of the 243 CAP patients included, 124 (51%) belonged to classes I, II and III, and 119 (49%) belonged to classes IV and V. One hundred and fifty six (64%) patients were admitted. Fifteen (6.2%) patients died, all of them belonging to classes IV and V. Forty four (18%) patients showed a poor outcome. Only one patient who was initially sent home had a poor outcome. The prognostic value of the PSI scale to predict mortality (ROC = 0.92; CI 95%, 0.88-0.95) was high. Our results confirm that the PSI scale is a good prognostic index in clinical practice for predicting mortality due to CAP. In order to use the PSI to decide the site of care of patients with CAP, not only the score obtained but also additional factors should be taken into account.

  17. Acquire information about neutrino parameters by detecting supernova neutrinos

    OpenAIRE

    Huang, Ming-Yang; Guo, Xin-Heng; Young, Bing-Lin

    2010-01-01

    We consider the supernova shock effects, the Mikheyev-Smirnov-Wolfenstein (MSW) effects, the collective effects, and the Earth matter effects in the detection of type II supernova neutrinos on the Earth. It is found that the event number of supernova neutrinos depends on the neutrino mass hierarchy, the neutrino mixing angle $\\theta_{13}$, and neutrino masses. Therefore, we propose possible methods to identify the mass hierarchy and acquire information about $\\theta_{13}$ and neutrino masses ...

  18. T cell responses in senior patients with community-acquired pneumonia related to disease severity.

    Science.gov (United States)

    Bian, Lu-Qin; Bi, Ying; Zhou, Shao-Wei; Chen, Zi-Dan; Wen, Jun; Shi, Jin; Mao, Ling; Wang, Ling

    2017-12-01

    Senior individuals older than 65 years of age are at a disproportionally higher risk of developing pneumonia. Impaired capacity to defend against airway infections may be one of the reasons. It is generally believed that weaker regulatory T cell responses may be beneficial to host defense against pathogens. In senior patients with community-acquired bacterial pneumonia, we investigated the frequencies and functions of regulatory T cells. Interestingly, we found that compared to age- and sex-matched healthy controls, senior pneumonia patients presented lower frequencies of Foxp3-expressing and Helios-expressing CD4 + T cells. The quantity of Foxp3 and Helios being expressed, measured by their mRNA transcription levels, was also lower in CD4 + T cells from pneumonia patients. Furthermore, following TCR and TGF-β stimulation, pneumonia patients presented impaired capacity to upregulate Foxp3 and Helios. Functional analyses revealed that CD4 + T cells from pneumonia patients secreted lower amounts of IL-10 and TGF-β, two cytokines critical to regulatory T cell-mediated suppression. Also, the expression of granzyme B and perforin, which were cytolytic molecules potentially utilized by regulatory T cells to mediate the elimination of antigen-presenting cells and effector T cells, were reduced in CD4 + CD25 + T cells from senior pneumonia patients. In addition, the CD4 + CD25 + T cells from senior pneumonia patients presented reduced capacity to suppress effector CD4 + and CD8 + T cell proliferation. Moreover, the value of pneumonia severity index was inversely correlated with several parameters of regulatory T cell function. Together, our results demonstrated that senior pneumonia patients presented a counterintuitive impairment in regulatory T cell responses that was associated with worse prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. C-reactive protein, procalcitonin, clinical pulmonary infection score, and pneumonia severity scores in nursing home acquired pneumonia.

    Science.gov (United States)

    Porfyridis, Ilias; Georgiadis, Georgios; Vogazianos, Paris; Mitis, Georgios; Georgiou, Andreas

    2014-04-01

    Patients with nursing home acquired pneumonia (NHAP) present a distinct group of lower respiratory track infections with different risk factors, clinical presentation, and mortality rates. To evaluate the diagnostic value of clinical pulmonary infection score (CPIS), C-reactive protein, and procalcitonin and to compare the accuracy of pneumonia severity scores (confusion, urea nitrogen, breathing frequency, blood pressure, ≥ 65 y of age [CURB-65]; pneumonia severity index; NHAP index; systolic blood pressure, multilobar involvement, albumin, breathing frequency, tachycardia, confusion, oxygen, arterial pH [SMART-COP]; and systolic blood pressure, oxygen, age > 65 y, breathing frequency [SOAR]) in predicting in-patient mortality from NHAP. Nursing home residents admitted to the hospital with acute respiratory illness were enrolled in the study. Subjects were classified as having NHAP (Group A) or other pulmonary disorders (Group B). Clinical, imaging, and laboratory data were assessed to compute CPIS and severity scores. C-reactive protein and procalcitonin were measured by immunonephelometry and immunoassay, respectively. Fifty-eight subjects were diagnosed with NHAP (Group A) and 29 with other pulmonary disorders (Group B). The mean C-reactive protein ± SD was 16.38 ± 8.6 mg/dL in Group A and 5.2 ± 5.6 mg/dL in Group B (P 1.1 ng/mL was an independent predictor of in-patient mortality. Of the pneumonia severity scores, CURB-65 showed greater accuracy in predicting in-patient mortality (area under the curve of 0.68, 95% CI 0.53-0.84, P = .06). CPIS, procalcitonin, and C-reactive protein are reliable for the diagnosis of NHAP. Procalcitonin and CURB-65 are accurate in predicting in-patient mortality in NHAP.

  20. Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

    Science.gov (United States)

    Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

    2012-01-01

    A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

  1. How Did Light Acquire a Velocity?

    Science.gov (United States)

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  2. Principles of Antibiotic Management of Community-Acquired Pneumonia.

    Science.gov (United States)

    Bender, Michael T; Niederman, Michael S

    2016-12-01

    Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae . We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Case report: unicameral bone cysts in a young patient with acquired generalized lipodystrophy.

    Science.gov (United States)

    Gregory, James M; Arkader, Alexandre; Bokhari, Aqiba; Bothari, Aqiba; Dormans, John P

    2010-05-01

    We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs.

  4. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

    Directory of Open Access Journals (Sweden)

    Mervi Toriseva

    Full Text Available Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13 in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/- and wild type (WT mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42% at day 21 in Mmp13(-/- mice. Granulation tissue in Mmp13(-/- mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/- mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/- mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/- granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/- mice compared to WT mice. Mmp13(-/- mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

  5. Acquiring information about neutrino parameters by detecting supernova neutrinos

    Science.gov (United States)

    Huang, Ming-Yang; Guo, Xin-Heng; Young, Bing-Lin

    2010-08-01

    We consider the supernova shock effects, the Mikheyev-Smirnov-Wolfenstein effects, the collective effects, and the Earth matter effects in the detection of type II supernova neutrinos on the Earth. It is found that the event number of supernova neutrinos depends on the neutrino mass hierarchy, the neutrino mixing angle θ13, and neutrino masses. Therefore, we propose possible methods to identify the mass hierarchy and acquire information about θ13 and neutrino masses by detecting supernova neutrinos. We apply these methods to some current neutrino experiments.

  6. Botulinum toxin in the management of sialorrhoea in acquired brain injury

    LENUS (Irish Health Repository)

    Carroll, A

    2016-06-01

    Sialorrhoea as a consequence of severe acquired brain injury can significantly negatively impact on quality of life. Medications used in its management have many side effects which can cause problems in the severely disabled. Botulinum toxin is an effective treatment of sialorrhoea in a number of neurological conditions but may also have a role to play in the management of sialorrhoea following severe ABI. We report on 4 cases of sialorrhoea following acquired brain injury causing a variety of problems, whose parotid glands were injected with Botulinum toxin type A (Dysport) 50mu each, under ultrasound guidance. All cases had a clinically and statistically significant reduction in drooling as measured by the teacher drooling scale (p=0.005) and carers Visual Analogue Scale (p=0.012). There were no side effects reported. Botulinum toxin is an effective treatment for sialorrhoea associated with acquired brain injury.

  7. Genetic study of intracranial aneurysms.

    Science.gov (United States)

    Yan, Junxia; Hitomi, Toshiaki; Takenaka, Katsunobu; Kato, Masayasu; Kobayashi, Hatasu; Okuda, Hiroko; Harada, Kouji H; Koizumi, Akio

    2015-03-01

    Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, leading to immediate death or severe disability. Identification of the genetic factors involved is critical for disease prevention and treatment. We aimed to identify the susceptibility genes for IAs. Exome sequencing was performed in 12 families with histories of multiple cases of IA (number of cases per family ≥3), with a total of 42 cases. Various filtering strategies were used to select the candidate variants. Replicate association studies of several candidate variants were performed in probands of 24 additional IA families and 426 sporadic IA cases. Functional analysis for the mutations was conducted. After sequencing and filtering, 78 variants were selected for the following reasons: allele frequencies of variants in 42 patients was significantly (PIA within ≥1 family; variants predicted damage to the structure or function of the protein by PolyPhen-2 (Polymorphism Phenotyping V2) and SIFT (Sorting Intolerance From Tolerant). We selected 10 variants from 9 genes (GPR63, ADAMST15, MLL2, IL10RA, PAFAH2, THBD, IL11RA, FILIP1L, and ZNF222) to form 78 candidate variants by considering commonness in families, known disease genes, or ontology association with angiogenesis. Replicate association studies revealed that only p.E133Q in ADAMTS15 was aggregated in the familial IA cases (odds ratio, 5.96; 95% confidence interval, 2.40-14.82; P=0.0001; significant after the Bonferroni correction [P=0.05/78=0.0006]). Silencing ADAMTS15 and overexpression of ADAMTS15 p.E133Q accelerated endothelial cell migration, suggesting that ADAMTS15 may have antiangiogenic activity. ADAMTS15 is a candidate gene for IAs. © 2015 American Heart Association, Inc.

  8. Family function and its relationship to injury severity and psychiatric outcome in children with acquired brain injury: a systematized review.

    Science.gov (United States)

    Lax Pericall, Maria Teresa; Taylor, Eric

    2014-01-01

    The psychological and psychiatric outcome of children with acquired brain injury is influenced by many variables. A review was undertaken to clarify the contribution of family function, how it relates to injury severity, and what particular aspects of family function influence psychological outcome in this group. A systematized review of the literature of studies published between 1970 and 2012 from OvidMedline, PsychoInfo, PsycARTICLES, and Cochrane was undertaken focusing on family function, injury severity, and psychiatric outcome. Thirty-six papers met the inclusion criteria. Injury severity was linked to the development of organic personality change. Family function before injury, measured by the Family Assessment Device or the Clinical Rating Scale, had a statistically significant effect on general psychological functioning in six out of eight studies. Family function had a significant effect for oppositional defiant disorder and secondary attention-deficit-hyperactivity disorder. The effects of family function may differ depending on the age of the child and the severity of the injury. Some styles of parenting moderated recovery. After injury, family function was related to the child's contemporaneous psychiatric symptoms. The level of evidence for these papers was 3 or 4 (Oxford Centre for Evidence-based Medicine criteria). Screening for some aspects of family functioning before injury and family function during the rehabilitation phase may identify children at risk of psychiatric disorders. © 2013 Mac Keith Press.

  9. The impact of blood glucose on community-acquired pneumonia

    DEFF Research Database (Denmark)

    Jensen, Andreas Vestergaard; Egelund, Gertrud Baunbæk; Andersen, Stine Bang

    2017-01-01

    Hyperglycaemia is common in patients with community-acquired pneumonia (CAP) and is a predictor of severe outcomes. Data are scarce regarding whether this association is affected by diabetes mellitus (DM) and also regarding its importance for severe outcomes in hospital. We determined the impact...

  10. The usefulness of the surgical knowledge and skills acquired via the university curriculum for doctors' medical practice several years after graduation.

    Science.gov (United States)

    Zyluk, Andrzej; Puchalski, Piotr; Szlosser, Zbigniew

    2015-01-01

    Teaching surgery during university curriculum comprises transferring theoretical knowledge traditionally and simultaneously acquiring manual skills, i.e., suturing, stitch removal, limb immobilization, catheterization, and assisting operations. Observations of doctors several years after graduation led to the reflection that teachers' ideas about surgical knowledge and skills that are useful in daily practice frequently fail to meet the facts of the case. The objective of this study was to determine which part of the surgical knowledge and skills taught via the university surgical curriculum proved to be useful in the daily practice of young doctors. A custom-made questionnaire was designed and mailed to 200 randomly chosen doctors who had graduated from the medical faculty at the authors' university 5 to 6 years previously. The questionnaire comprised 9 items concerning the knowledge and skills that proved to be the most useful in participants' daily practice, regardless of their specialty. A total of 64 completed questionnaires were returned (32% of 200 sent) and were the subject of analysis. The most useful knowledge in daily practice was that acquired from general surgery, followed by oncological and vascular surgery. The most useful was knowledge about the rational interpretation of clinical symptoms and signs acquired from examination of the patient, followed by arriving at an accurate diagnosis through logical analysis, and next developing "oncological sensitivity" to diagnosing neoplasms. The most effective teaching model was specialized outpatient clinic rounds, followed by training manual skills on a model and classical ward-round teaching. The most frequently learned (acquired) manual skills were removal of stitches, rectal examination, and examination of the abdomen. Of these skills, the most useful in daily practice appeared to be removal of stitches, catheterization of the urinary bladder, and wound suturing. Learning and practicing manual skills

  11. Analysis of stable isotope assisted metabolomics data acquired by GC-MS

    International Nuclear Information System (INIS)

    Wei, Xiaoli; Shi, Biyun; Koo, Imhoi; Yin, Xinmin; Lorkiewicz, Pawel; Suhail, Hamid; Rattan, Ramandeep; Giri, Shailendra; McClain, Craig J.

    2017-01-01

    Stable isotope assisted metabolomics (SIAM) measures the abundance levels of metabolites in a particular pathway using stable isotope tracers (e.g., 13 C, 18 O and/or 15 N). We report a method termed signature ion approach for analysis of SIAM data acquired on a GC-MS system equipped with an electron ionization (EI) ion source. The signature ion is a fragment ion in EI mass spectrum of a derivatized metabolite that contains all atoms of the underivatized metabolite, except the hydrogen atoms lost during derivatization. In this approach, GC-MS data of metabolite standards were used to recognize the signature ion from the EI mass spectra acquired from stable isotope labeled samples, and a linear regression model was used to deconvolute the intensity of overlapping isotopologues. A mixture score function was also employed for cross-sample chromatographic peak list alignment to recognize the chromatographic peaks generated by the same metabolite in different samples, by simultaneously evaluating the similarity of retention time and EI mass spectrum of two chromatographic peaks. Analysis of a mixture of 16 13 C-labeled and 16 unlabeled amino acids showed that the signature ion approach accurately identified and quantified all isotopologues. Analysis of polar metabolite extracts from cells respectively fed with uniform 13 C-glucose and 13 C-glutamine further demonstrated that this method can also be used to analyze the complex data acquired from biological samples. - Highlights: • A signature ion approach is developed for analysis of stable isotope GC-MS data. • GC-MS data of compound standards are used for selection of the signature ion. • Linear regression model is used to deconvolute the overlapping isotopologue peaks. • The developed method was tested by known compounds and biological samples.

  12. Foodborne listeriosis acquired in hospitals.

    Science.gov (United States)

    Silk, Benjamin J; McCoy, Morgan H; Iwamoto, Martha; Griffin, Patricia M

    2014-08-15

    Listeriosis is characterized by bacteremia or meningitis. We searched for listeriosis case series and outbreak investigations published in English by 2013, and assessed the strength of evidence for foodborne acquisition among patients who ate hospital food. We identified 30 reports from 13 countries. Among the case series, the median proportion of cases considered to be hospital-acquired was 25% (range, 9%-67%). The median number of outbreak-related illnesses considered to be hospital-acquired was 4.0 (range, 2-16). All patients were immunosuppressed in 18 of 24 (75%) reports with available data. Eight outbreak reports with strong evidence for foodborne acquisition in a hospital implicated sandwiches (3 reports), butter, precut celery, Camembert cheese, sausage, and tuna salad (1 report each). Foodborne acquisition of listeriosis among hospitalized patients is well documented internationally. The number of listeriosis cases could be reduced substantially by establishing hospital policies for safe food preparation for immunocompromised patients and by not serving them higher-risk foods. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. A Case of Fibrillary Glomerulonephritis Associated with Thrombotic Microangiopathy and Anti-Glomerular Basement Membrane Antibody

    Directory of Open Access Journals (Sweden)

    Akishi Momose

    2015-02-01

    Full Text Available We present the first report of a case of fibrillary glomerulonephritis (FGN associated with thrombotic microangiopathy (TMA and anti-glomerular basement membrane antibody (anti-GBM antibody. A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction. Laboratory data revealed normocytic-normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia, increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative results for both direct and indirect Coombs tests. Based on these results, we diagnosed TMA. Assays conducted several days later indicated a disintegrin-like and metalloprotease with a thrombospondin motif 13 (ADAMTS13 activity of 31.6%, and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day, and mild convulsions developed. Based on magnetic resonance imaging of the head, the patient was diagnosed with reversible posterior leukoencephalopathy syndrome. Hypertension persisted despite administration of multiple antihypertensive agents, and the patient experienced a sudden generalized seizure. Computed tomography of the head showed multiple cerebral hemorrhages. However, his blood pressure subsequently decreased and the platelet count increased. TMA remitted following 36 plasma exchange sessions, but renal function was not restored, and maintenance hemodialysis was continued. The patient was discharged on the 119th day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM antibody were closely related.

  14. A Bias for the Natural? Children's Beliefs about Traits Acquired through Effort, Bribes, or Medicine

    Science.gov (United States)

    Lockhart, Kristi L.; Keil, Frank C.; Aw, Justine

    2013-01-01

    Three studies compared beliefs about natural and late blooming positive traits with those acquired through personal effort, extrinsic rewards or medicine. Young children (5-6 years), older children (8-13 years), and adults all showed a strong bias for natural and late blooming traits over acquired traits. All age groups, except 8- to 10-year-olds,…

  15. Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report.

    Science.gov (United States)

    Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Unlu, Serkan; Ertem, Kadir; Nizam, Ilknur

    2014-08-01

    Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. Copyright © 2014. Published by Elsevier Ltd.

  16. The impact of community-acquired pneumonia on the health-related quality-of-life in elderly.

    Science.gov (United States)

    Mangen, Marie-Josée J; Huijts, Susanne M; Bonten, Marc J M; de Wit, G Ardine

    2017-03-14

    The sustained health-related quality-of-life of patients surviving community-acquired pneumonia has not been accurately quantified. The aim of the current study was to quantify differences in health-related quality-of-life of community-dwelling elderly with and without community-acquired pneumonia during a 12-month follow-up period. In a matched cohort study design, nested in a prospective randomized double-blind placebo-controlled trial on the efficacy of the 13-valent pneumococcal vaccine in community-dwelling persons of ≥65 years, health-related quality-of-life was assessed in 562 subjects hospitalized with suspected community-acquired pneumonia (i.e. diseased cohort) and 1145 unaffected persons (i.e. non-diseased cohort) matched to pneumonia cases on age, sex, and health status (EQ-5D-3L-index). Health-related quality-of-life was determined 1-2 weeks after hospital discharge/inclusion and 1, 6 and 12 months thereafter, using Euroqol EQ-5D-3L and Short Form-36 Health survey questionnaires. One-year quality-adjusted life years (QALY) were estimated for both diseased and non-diseased cohorts. Separate analyses were performed for pneumonia cases with and without radiologically confirmed community-acquired pneumonia. The one-year excess QALY loss attributed to community-acquired pneumonia was 0.13. Mortality in the post-discharge follow-up year was 8.4% in community-acquired pneumonia patients and 1.2% in non-diseased persons (p pneumonia patients, compared to non-diseased persons, but differences in health-related quality-of-life between radiologically confirmed and non-confirmed community-acquired pneumonia cases were not statistically significant. Community-acquired pneumonia was associated with a six-fold increased mortality and 16% lower quality-of-life in the post-discharge year among patients surviving hospitalization for community-acquired pneumonia, compared to non-diseased persons. ClinicalTrials.gov, NCT00812084 .

  17. Possibilities of predicting of the non-severe community-acquired pneumonia outcomes in patients with type 2 diabetes mellitus or chronic heart failure

    Directory of Open Access Journals (Sweden)

    O. S. Makharynska

    2014-06-01

    Full Text Available Aim. Сommunity-acquired pneumonia is life-threatening disease with level of fatal events in hospitals within 12-36 %. In turn, presence of congestive heart failure or type 2 diabetes increases the risk of adverse outcomes in patients with community-acquired pneumonia. Methods and results. In the modern world’s literature there are many models predicting clinical outcomes of community-acquired pneumonia, but none of them includes questionnaires data for such patients. In our study, we used two questionnaires: "The scale of assessment community-acquired pneumonia" R. el Moussaoui and CapSym-12. C Сonclusion. Using logistic regression, we have found statistically significant indices sample questionnaires prognostic opportunities which were used in this study to assess the health and dynamics of symptoms of community-acquired pneumonia and that allows us to predict the outcome community-acquired pneumonia.

  18. Clinical, general, hemocoagulation and pathologicanatomical features of patients with moderate and severe community acquired pneumonia by the data of retrospective analysis

    Directory of Open Access Journals (Sweden)

    Pertseva T.A.

    2017-10-01

    Full Text Available According to literature data, patients with community acquired pneumonia (CAP fall into several groups of unfavorable prognostic factors. Development of thrombotic complications is one of causes of mortality of hospitalized patients. In this case systemic inflammation, which is always present in moderate and severe CAP, is the starting mechanism of formation of disorders in the hemostasis system. The aim of our work was to determine anamnestic, clinical, laboratory and pathologic anatomical features in patients with CAP, taking into account markers of systemic inflammation and coagulogram indices, as well as predicting the occurrence of complications. In the course of the work, a retrospective analysis of 151 medical histories of hospitalized patients with CAP was made. We analyzed anthropometric indicators, complaints at the time of hospitalization, results of physical examination, results of the chest X-ray, clinical and laboratory indicators, microbiological sputum analysis and to assess the possibility of thrombotic complications a RAM scale was used. It was found that late asking for medical help, the presence of mixed infection, underestimation of the severity of condition and severe systemic inflammation increase the risk of lethal outcome in patients with CAP. Considering a high risk of thrombosis in patients with CAP, it is necessary to assess the risk of thrombotic complications with the help of special scales, as well as timely detection and correction of disorders from the hemostasis system.

  19. Differences in microbiological profile between community-acquired, healthcare-associated and hospital-acquired infections.

    Science.gov (United States)

    Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Sarmento, António

    2013-01-01

    Microbiological profiles were analysed and compared for intra-abdominal, urinary, respiratory and bloodstream infections according to place of acquisition: community-acquired, with a separate analysis of healthcare-associated, and hospital-acquired. Prospective cohort study performed at a university tertiary care hospital over 1 year. Inclusion criteria were meeting the Centers for Disease Control definition of intra-abdominal, urinary, respiratory and bloodstream infections. A total of 1035 patients were included in the study. More than 25% of intra-abdominal infections were polymicrobial; multi-drug resistant gram-negatives were 38% in community-acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was the most prevalent among urinary infections: 69% in community-acquired, 56% in healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens were 10% in healthcare-associated and 3% in community-acquired and hospital-acquired. In respiratory infections Streptococcus pneumoniae was the most prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and hospital-acquired (24%). A significant association was found between MRSA respiratory infection and hospitalization in the previous year (adjusted OR = 6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic therapy (adjusted OR = 5.7); no cases were documented among patients without risk factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare-associated and 19% in hospital-acquired infection. This study shows that healthcare-associated has a different microbiologic profile than those from community or hospital acquired for the four main focus of infection. Knowledge of this fact is important because the existing guidelines for community-acquired are not entirely applicable for this group of patients.

  20. Audit Domain Acquire And Implement dengan Cobit 4.1 pada PT Erajaya Swasembada Tbk

    Directory of Open Access Journals (Sweden)

    Viany Utami Tjhin

    2014-12-01

    Full Text Available The main priority aspect of information and communication technologies is given to control mechanisms, both internal and external in enterprises. It ensures that the reports and the decisions received and generated by the management will support their decision-making. The decisions have honesty and high integrity based on the results of the audit conducted on systems of information and communication technology. The objective of this research is to deliver audit reports of information systems for management and make recommendations on the audit findings in PT Erajaya Swasembada Tbk. Business processes studied included sales, purchasing, finance, and the warehouse. The system used was "Erajaya Live Application Server" and ERP (Enterprise Resource Planning-based. This research used thedomain of COBIT 4.1: Acquire and Implement. The domain included several sub-domains, which were:identify automated solutions (AI1, acquire and maintain application software (AI2, acquire and maintain technology infrastructure (AI3, enable operation and use (AI4, procure IT resources (AI5, manage changes (AI6, and install and accredit solutions and changes (AI7. Data were collected from interviewing IT Department, distributing questionnaires to respondents, and observing the business processes of this enterprise. Research obtained 57 audit findings on IT implementation. The results of process reference model formulation are 3 findings on AI1subdomain, 5 findings on AI2subdomain, 9 findings on AI3subdomain, 6 findings on AI4 subdomain, 11 findings on AI5subdomain, 13 findings pada AI6subdomain, and 10 findings on AI7subdomain. The level of maturity model of this domain, Acquire and Implement (AI, was found on level 3.

  1. Informant Report of Financial Capacity for Individuals With Chronic Acquired Brain Injury: An Assessment of Informant Accuracy.

    Science.gov (United States)

    Sunderaraman, Preeti; Cosentino, Stephanie; Lindgren, Karen; James, Angela; Schultheis, Maria

    2018-03-29

    Primarily, to investigate the association between informant report and objective performance on specific financial capacity (FC) tasks by adults with chronic, moderate to severe acquired brain injury, and to examine the nature of misestimates by the informants. Cross-sectional design. A postacute, community-based rehabilitation center. Data were obtained from 22 chronic acquired brain injury (CABI) adults, mean age of 46.6 years (SD = 8.67), mean years of education of 13.45 years (SD = 2.15), with moderate to severe acquired brain injury (86% had traumatic brain injury), with a mean postinjury period of 17.14 years (SD = 9.5). Whereas the CABI adults completed the Financial Competence Assessment Inventory interview-a combination of self-report and performance-based assessment, 22 informants completed a specifically designed parallel version of the interview. Pearson correlations and 1-sample t tests based on the discrepancy scores between informant report and CABI group's performance were used. The CABI group's performance was not associated with its informant's perceptions. One-sample t tests revealed that informants both underestimated and overestimated CABI group's performance. Results indicate lack of correspondence between self- and informant ratings. Further investigation revealed that misestimations by informants occurred in contrary directions with CABI adults' performance being inaccurately rated. These findings raise critical issues related to assuming that the informant report can be used as a "gold standard" for collecting functional data related to financial management, and the idea that obtaining objective data on financial tasks may represent a more valid method of assessing financial competency in adults with brain injury.

  2. Application of 13C-labeling and 13C-13C COSY NMR experiments in the structure determination of a microbial natural product.

    Science.gov (United States)

    Kwon, Yun; Park, Sunghyouk; Shin, Jongheon; Oh, Dong-Chan

    2014-08-01

    The elucidation of the structures of complex natural products bearing many quaternary carbons remains challenging, even in this advanced spectroscopic era. (13)C-(13)C COSY NMR spectroscopy shows direct couplings between (13)C and (13)C, which comprise the backbone of a natural product. Thus, this type of experiment is particularly useful for natural products bearing consecutive quaternary carbons. However, the low sensitivity of (13)C-based NMR experiments, due to the low natural abundance of the (13)C nucleus, is problematic when applying these techniques. Our efforts in the (13)C labeling of a microbial natural product, cyclopiazonic acid (1), by feeding (13)C-labeled glucose to the fungal culture, enabled us to acquire (13)C-(13)C COSY NMR spectra on a milligram scale that clearly show the carbon backbone of the compound. This is the first application of (13)C-(13)C COSY NMR experiments for a natural product. The results suggest that (13)C-(13)C COSY NMR spectroscopy can be routinely used for the structure determination of microbial natural products by (13)C-enrichment of a compound with (13)C-glucose.

  3. Microangiopatias trombóticas: púrpura trombocitopênica trombótica e síndrome hemolítico-urêmica Thrombotic microangiopathies: thrombotic thrombocytopenic purpura / hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Maria Goretti Polito

    2010-09-01

    disease that may play a paramount role in particular in familial and recurrent forms. In the case of diarrhea-associated HUS (D+HUS, renal endothelial damage is mediated (at least in large part by the bacterial agent Shigatoxin (Stx, which is actually a family of toxins elaborated by certain strains of Escherichia coli and Shigella dysenteriae. Outcome is usually good in childhood, Shiga toxin-associated HUS, whereas renal and neurological sequelae are more frequently reported in adult, atypical, and familial forms of HUS and in TTP. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease ADAMTS13, due to deficiency of ADAMTS13 can be genetic or more common, acquired, resulting from autoimmune production of inhibitory anti-ADAMTS13 antibodies, that causes TTP. During the last decade, atypical HUS (aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH, factor I (CFI and membrane cofactor protein (MCP or CD46, or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13. Platelet transfusions are contraindicated. Plasma infusion or exchange (PE is the only treatment of proven efficacy.

  4. Music evoked autobiographical memory after severe acquired brain injury: preliminary findings from a case series.

    Science.gov (United States)

    Baird, A; Samson, S

    2014-01-01

    Music evoked autobiographical memories (MEAMs) have been characterised in the healthy population, but not, to date, in patients with acquired brain injury (ABI). Our aim was to investigate music compared with verbal evoked autobiographical memories. Five patients with severe ABI and matched controls completed the experimental music (MEAM) task (a written questionnaire) while listening to 50 "Number 1 Songs of the Year" (from 1960 to 2010). Patients also completed the Autobiographical Memory Interview (AMI) and a standard neuropsychological assessment. With the exception of Case 5, who reported no MEAMs and no autobiographical incidents on the AMI and who also had impaired pitch perception, the range of frequency and type of MEAMs in patients was broadly in keeping with their matched controls. The relative preservation of MEAMs in four cases was particularly noteworthy given their impaired verbal and/or visual anterograde memory, and in three cases, autobiographical memory impairment. The majority of MEAMs in both cases and matched controls were of a person/people or a period of life. In three patients music was more efficient at evoking autobiographical memories than the AMI verbal prompts. This is the first study of MEAMs after ABI. The findings suggest that music is an effective stimulus for eliciting autobiographical memories, and may be beneficial in the rehabilitation of autobiographical amnesia, but only in patients without a fundamental deficit in autobiographical recall memory and intact pitch perception.

  5. DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.

    Directory of Open Access Journals (Sweden)

    Marion Avril

    Full Text Available During blood stage infection, Plasmodium falciparum infected erythrocytes (IE bind to host blood vessels. This virulence determinant enables parasites to evade spleen-dependent killing mechanisms, but paradoxically in some cases may reduce parasite fitness by killing the host. Adhesion of infected erythrocytes is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1, a family of polymorphic adhesion proteins encoded by var genes. Whereas cerebral binding and severe malaria are associated with parasites expressing DC8 and DC13 var genes, relatively little is known about the non-brain endothelial selection on severe malaria adhesive types. In this study, we selected P. falciparum-IEs on diverse endothelial cell types and demonstrate that DC8 and DC13 var genes were consistently among the major var transcripts selected on non-brain endothelial cells (lung, heart, bone marrow. To investigate the molecular basis for this avid endothelial binding activity, recombinant proteins were expressed from the predominant upregulated DC8 transcript, IT4var19. In-depth binding comparisons revealed that multiple extracellular domains from this protein bound brain and non-brain endothelial cells, and individual domains largely did not discriminate between different endothelial cell types. Additionally, we found that recombinant DC8 and DC13 CIDR1 domains exhibited a widespread endothelial binding activity and could compete for DC8-IE binding to brain endothelial cells, suggesting they may bind the same host receptor. Our findings provide new insights into the interaction of severe malaria adhesive types and host blood vessels and support the hypothesis that parasites causing severe malaria express PfEMP1 variants with a superior ability to adhere to diverse endothelial cell types, and may therefore endow these parasites with a growth and transmission advantage.

  6. A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

    Science.gov (United States)

    Viner, Maya; Murakhovskaya, Irina

    2017-07-01

    : Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

  7. Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-2-0138 TITLE: Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome PRINCIPAL INVESTIGATOR...Immunogenicity to Metals Affects Orthopaedic pla t Outcome 5b. GRANT NUMBER W91ZSQ0135N646 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nadim James...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEM ENTARY NOTES 14. ABSTRACT The effects of battlefield

  8. Association of hypercapnia on admission with increased length of hospital stay and severity in patients admitted with community-acquired pneumonia: a prospective observational study from Pakistan.

    Science.gov (United States)

    Iqbal, Nousheen; Irfan, Muhammad; Zubairi, Ali Bin Sarwar; Awan, Safia; Khan, Javaid A

    2017-06-15

    To determine whether the presence of hypercapnia on admission in adult patients admitted to a university-based hospital in Karachi, Pakistan with community-acquired pneumonia (CAP) correlates with an increased length of hospital stay and severity compared with no hypercapnia on admission. A prospective observational study. Tertiary care hospital in Karachi, Pakistan. Patients who met the inclusion criteria were enrolled in the study. The severity of pneumonia was assessed by CURB-65 and PSI scores. An arterial blood gas analysis was obtained within 24 hours of admission. Based on arterial PaCO 2 levels, patients were divided into three groups: hypocapnic (PaCO 2 45 mm Hg) and normocapnic (PaCO 2 <35-45 mm Hg). The primary outcome was the association of hypercapnia on admission with mean length of hospital stay. Secondary outcomes were the need for mechanical ventilation, ICU admission and in-hospital mortality. A total of 295 patients of mean age 60.20±17.0 years (157 (53.22%) men) were enrolled over a 1-year period. Hypocapnia was found in 181 (61.35%) and hypercapnia in 57 (19.32%) patients. Hypercapnic patients had a longer hospital stay (mean 9.27±7.57 days), increased requirement for non-invasive mechanical ventilation (NIMV) on admission (n=45 (78.94%)) and longer mean time to clinical stability (4.39±2.0 days) compared with the other groups. Overall mortality was 41 (13.89%), but there was no statistically significant difference in mortality (p=0.35) and ICU admission (p=0.37) between the three groups. On multivariable analysis, increased length of hospital stay was associated with NIMV use, ICU admission, hypercapnia and normocapnia. Hypercapnia on admission is associated with severity of CAP, longer time to clinical stability, increased length of hospital stay and need for NIMV. It should be considered as an important criterion to label the severity of the illness and also a determinant of patients who will require a higher level of hospital

  9. Clinical role of Cefixime in community-acquired infections.

    Science.gov (United States)

    Dreshaj, Sh; Doda-Ejupi, T; Tolaj, I Q; Mustafa, A; Kabashi, S; Shala, N; Geca, Nj; Aliu, A; Daka, A; Basha, N

    2011-01-01

    Cefixime is an oral third generation cephalosporin, frequently used in respiratory tract infections (RTI) in the pediatric population. However, in some publications cefixime has demonstrated poor efficacy against staphylococci and streptococci. of this study was to evaluate the efficacy of cefixime in the treatment of community-acquired infections in a country where parenteral third generation cephalosporins have been used for a long time. The present study was designed to assess the clinical efficacy, bacteriological eradication rates and tolerability of cefixime in children with community-acquired upper RTI (URTI), lower RTI (LRTI) and uncomplicated urinary tract infections (UTI). The study was prospective, open, and included 89 patients, from 6 months to 28 years, of both sexes, with the diagnosis of community-acquired URTI, LRTI and UTI. The treatment with cefixime was successful in 30/30 (100%) patients suffering from acute otitis media (AOM), in 10/12 (83.3%) with acute sinusitis, in 12/12 patients (100%) with pneumonia, in 31/35 (88.57) with uncomplicated UTI. The antibiotic was well tolerated. In 10 days treatment we recorded one case (1.3%) with acute gastroenteritis and two cases (2.6%) of maculopapular rash. Side-effects were transient and disappeared after finishing therapy in all three of the cases. Community-acquired infections, such as AOM, LRTI and UTI, caused by susceptible pathogens, can be treated with cefixime, as a good choice for a successful clinical response.

  10. First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

    Science.gov (United States)

    Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

    2011-01-01

    Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

  11. Oral Antibiotics for Community acquired Pneumonia with Chest indrawing in Children Aged Below Five Years: A Systematic Review.

    Science.gov (United States)

    Lodha, Rakesh; Randev, Shivani; Kabra, Sushil K

    2016-06-08

    To determine the efficacy of oral antibiotics in under-five children with pneumonia and chest indrawing. We included controlled clinical trials (randomized or quasi randomized) that compared the efficacy of oral antibiotics versus parenteral antibiotics for treatment of community acquired pneumonia with chest indrawing (severe pneumonia as defined by the World Health Organizations guidelines) in children below 60 months of age. Data were extracted and managed using RevMan software. Main outcome variables were: treatment failure rate, relapse rate, death rate, need for hospitalization, and severe adverse effects. We identified four randomized controlled trials involving 4400 children who were diagnosed to have severe pneumonia but were feeding well and not hypoxic. Baseline characteristics of children in the two treatment arms (oral and parenteral antibiotics) were similar. In two studies, oral antibiotics were administered on an ambulatory basis, while in two, oral antibiotics were used in hospitalized children. Failure rate in children receiving oral antibiotics was 13% (288/2208) while that in children receiving parenteral antibiotics was 13.8% (302/2183) (OR 0.93; 95% CI 0.78, 1.11). Failure rates were not affected by the type of oral antibiotic, or presence of wheeze. Relapse rates, hospitalization or serious adverse events were similar in the two groups. Children with tachypnea with chest indrawing without signs and symptoms of very severe pneumonia may be treated with oral antibiotics.

  12. 13 CFR 143.32 - Equipment.

    Science.gov (United States)

    2010-01-01

    ... awarding agency. (d) Management requirements. Procedures for managing equipment (including replacement... return. (e) Disposition. When original or replacement equipment acquired under a grant or subgrant is no... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Equipment. 143.32 Section 143.32...

  13. A new look at acquired heart diseases in a contemporary sub-Saharan African pediatric population: the case of Yaoundé, Cameroon.

    Science.gov (United States)

    Nkoke, Clovis; Menanga, Alain; Boombhi, Jerome; Chelo, David; Kingue, Samuel

    2015-12-01

    Acquired heart diseases (AHD) in children cause significant morbidity and mortality especially in low resource settings. There is limited description of acquired childhood heart diseases in Cameroon, making it difficult to estimate its current contribution to childhood morbidity and mortality. Echocardiography is the main diagnostic modality in low resource settings and has a key role in the characterization and management of these disorders. We aimed to determine the prevalence and spectrum of AHD in children in Yaoundé-Cameroon, in an era of echocardiography. These data are needed for health service and policy formulation. Echocardiography records from August 2003 to December 2013 were reviewed. Echocardiography records of children ≤18 years with an echocardiographic diagnosis of a definite AHD were identified and relevant data extracted from their records. One hundred and fifty eight children (13.4%) ≤18 years had an AHD. The mean [± standard deviations (SD)] age was 11.9 (±4.4) years .The most common affected age group was 15-18 years (36.1%). Heart failure (20.3%), suspicion of rheumatic heart disease (RHD) (12.0%) and the presence of a heart murmur (8.9%) were the most common indications for echocardiography. RHD (41.1%), pericardial disease (25.3%), dilated cardiomyopathy (DCM) (15.8%) and endomyocardial fibrosis (EMF) (13.9%) were the most common AHD. Cor pulmonale was rare (1.3%). Fifty-seven (87.7%) children with RHD had mitral regurgitation alone or in combination with other heart valve lesions and 63.3% of the lesions were severe. RHD remains the most common AHD in children in this setting and is frequently severe. Multicenter collaborative studies will help to better describe the pattern of AHD and there should be a renewed focus on the prevention of RHD.

  14. Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2017-11-01

    Full Text Available Objective The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Methods Six samples (three in each group were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs between the two groups. Results 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypo-methylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3, acyl-CoA synthetase long chain family member 1 (ACSL1, ryanodine receptor 1 (RYR1, acyl-CoA oxidase 2 (ACOX2, peroxisome proliferator activated receptor-gamma2 (PPARG2, netrin 1 (NTN1, ras and rab interactor 2 (RIN2, microtubule associated protein RP/EB family member 1 (MAPRE1, ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2, myomesin 1 (MYOM1, zinc finger, DHHC type containing 13 (ZDHHC13, and SH3 and PX domains 2B (SH3PXD2B. The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. Conclusion In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3

  15. Myocardial perfusion quantification using simultaneously acquired 13 NH3 -ammonia PET and dynamic contrast-enhanced MRI in patients at rest and stress.

    Science.gov (United States)

    Kunze, Karl P; Nekolla, Stephan G; Rischpler, Christoph; Zhang, Shelley HuaLei; Hayes, Carmel; Langwieser, Nicolas; Ibrahim, Tareq; Laugwitz, Karl-Ludwig; Schwaiger, Markus

    2018-04-19

    Systematic differences with respect to myocardial perfusion quantification exist between DCE-MRI and PET. Using the potential of integrated PET/MRI, this study was conceived to compare perfusion quantification on the basis of simultaneously acquired 13 NH 3 -ammonia PET and DCE-MRI data in patients at rest and stress. Twenty-nine patients were examined on a 3T PET/MRI scanner. DCE-MRI was implemented in dual-sequence design and additional T 1 mapping for signal normalization. Four different deconvolution methods including a modified version of the Fermi technique were compared against 13 NH 3 -ammonia results. Cohort-average flow comparison yielded higher resting flows for DCE-MRI than for PET and, therefore, significantly lower DCE-MRI perfusion ratios under the common assumption of equal arterial and tissue hematocrit. Absolute flow values were strongly correlated in both slice-average (R 2  = 0.82) and regional (R 2  = 0.7) evaluations. Different DCE-MRI deconvolution methods yielded similar flow result with exception of an unconstrained Fermi method exhibiting outliers at high flows when compared with PET. Thresholds for Ischemia classification may not be directly tradable between PET and MRI flow values. Differences in perfusion ratios between PET and DCE-MRI may be lifted by using stress/rest-specific hematocrit conversion. Proper physiological constraints are advised in model-constrained deconvolution. © 2018 International Society for Magnetic Resonance in Medicine.

  16. 13 CFR 120.911 - Land contributions.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Land contributions. 120.911 Section 120.911 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development... Project Property) previously acquired by the Borrower. [68 FR 57987, Oct. 7, 2003] ...

  17. Learning-by-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo Gaetano; Moreira, Solon; Rabbiosi, Larissa

    2016-01-01

    In horizontal acquisitions, the post-acquisition integration of the R&D function often damages the inventive labor force and results in lower innovative productivity of acquired inventors. In this paper we study post-acquisition integration in terms of R&D team reorganization-i.e., the creation...... of new teams with both inventors of the acquiring and acquired firms-and assess the impact of this integration action in the period that immediately follows the acquisition. Drawing on social identity and self-categorization theories, we argue that R&D team reorganization increases the acquired inventors...

  18. Acquired alopecia, mental retardation, short stature, microcephaly, and optic atrophy

    NARCIS (Netherlands)

    Hennekam, R. C.; Renckens-Wennen, E. G.

    1990-01-01

    We report on a female patient who had acquired total alopecia, short stature, microcephaly, optic atrophy, severe myopia, and mental retardation. A survey of published reports failed to show an identical patient, despite various similar cases

  19. Age-related pattern and monocyte-acquired haemozoin associated production of erythropoietin in children with severe malarial anaemia in Ghana.

    Science.gov (United States)

    Abugri, James; Tetteh, John Kweku Amissah; Oseni, Lateef Adebayo; Mensah-Brown, Henrietta Esi; Delimini, Rupert Kantunye; Obuobi, David Osei; Akanmori, Bartholomew Dicky

    2014-08-20

    Malaria continues to be a global health challenge, affecting more than half the world's population and causing approximately 660,000 deaths annually. The majority of malaria cases are caused by Plasmodium falciparum and occur in sub-Saharan Africa. One of the major complications asscociated with malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the parasite. Anaemia due to falciparum malaria in children has multifactorial pathogenesis, which includes suppression of bone marrow activity. Recent studies have shown that haemozoin, which is a by-product of parasite haemoglobin digestion, may play an important role in suppression of haemoglobin production, leading to anaemia. In this study we correlated the levels of erythropoietin (EPO), as an indicator of stimulation of haemoglobin production, to the levels of monocyte acquired haemozoin in children with both severe and uncomplicated malaria. There was a significantly negative correlation between levels of haemozoin-containing monocytes and EPO, which may suggest that haemozoin suppresses erythropoiesis in severe malaria. A multiple linear regression analysis and simple bar was used to investigate associations between various haematological parameters. To examine the levels of erythropoietin in the age categories, the levels of erythropoietin was measured using a commercial Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used to determine percentage pigment containing monocytes. The haemozoin containing monocytes was expressed as a percentage of the total number of monocytes. To obtain the number of haemozoin containing monocytes/μL the percentage of haemozoin containing monocytes was multiplied by the absolute number of monocytes/μL from the automated haematology analyzer. The levels of erythropoietin in younger children (<3 years) was significantly higher than in older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005). Haemozoin

  20. Frequency of hospital acquired hyponatremia in a pediatric tertiary care setting

    International Nuclear Information System (INIS)

    Bibi, S.; Haq, A.U.; Billo, A.G.; Bibi, S.; Gilani, S.Y.H.; Shah, S.R.A.

    2015-01-01

    Background: Hyponatremia is the most commonly encountered electrolyte disorder in children. In our country the epidemiology of hospital acquired hyponatremia has hardly ever been explored whereas the administration of hypotonic IV fluids is widely practiced here. Therefore we pioneered to conduct this study to determine the frequency of hospital acquired hyponatremia. Method: This was a cross sectional study carried out at Aga Khan University Hospital, Karachi in paediatric ward and ICU over a period of 12 months. All children (>1 month and <15 years of age) admitted in paediatric units and on maintenance IV fluids who had serum sodium level measured on admission were included in the study and followed to identify patients who had a drop in serum sodium during hospitalization. Informed consent was taken from parents and collected data was recorded on a proforma. Results: A total of 865 patients were enrolled in the study. Hyponatremia was recorded in 405 patients on admission (46.8 percentage) while hospital acquired hyponatremia was documented in 240. children (27.7 percentage). Out of these 142 (59.2 percentage) were male and 98 (40.8 percentage) were female. Mean age of children in hospital acquired hyponatremia group was 60.67 months. Severity of hospital acquired hyponatremia was recorded as mild in 191 (79.6 percentage), moderate in 35 (14.6 percentage) and severe in 14 (5.8) children. Major disease categories included gastrointestinal disorder (30.4 percentage), respiratory illness (12.5 percentage), oncological disease (16.3 percentage), cardiovascular disease (11.7 percentage), infectious disease (9.2 percentage) and neurological illness (8.3 percentage). Conclusion: Hospital acquired hyponatremia is frequently encountered in our hospitalized children with majority of them receiving hypotonic IV solutions. (author)

  1. 13 CFR 143.33 - Supplies.

    Science.gov (United States)

    2010-01-01

    ... residual inventory of unused supplies exceeding $5,000 in total aggregate fair market value upon... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Supplies. 143.33 Section 143.33..., and Subawards § 143.33 Supplies. (a) Title. Title to supplies acquired under a grant or subgrant will...

  2. Acquired neuropathies.

    Science.gov (United States)

    Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

    2013-09-01

    Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

  3. Understanding and Targeting Epigenetic Alterations in Acquired Bone Marrow Failure

    Science.gov (United States)

    2014-05-01

    hematopoiesis, lym- phatics and immunity. Blood. 2013 Nov 13. [Epub ahead of print] 8. West RR, Hsu AP, Holland SM, Cuellar- Rodriguez J, Hickstein DD. Acquired...MA 02114 11Department of Molecular Biology and 12Department of Bioinformatics and Computational Biology, Genentech, South San Francisco , CA 94080...other groups (Subramanian et al., 2005). We identified gene sets enriched in HSCs (Ramalho- Santos et al., 2002) and apoptosis (http:// www.genome.jp

  4. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Joselli S Silva

    Full Text Available Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02 in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4 compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01. These changes in the spleen were associated with higher frequency of severe disease (7/12 in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01 splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

  5. Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice.

    Science.gov (United States)

    Zheng, Wenhao; Feng, Zhenhua; You, Shengban; Zhang, Hui; Tao, Zhenyu; Wang, Quan; Chen, Hua; Wu, Yaosen

    2017-04-01

    Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Fisetin, a polyphenol extracted from fruits and vegetables, has been reported to have anti-inflammatory effects. Our study aimed to investigate the effect of fisetin on OA both in vitro and in vivo. In vitro, chondrocytes were pretreated with fisetin alone or fisetin combined with sirtinol (an inhibitor of SIRT1) for 2h before IL-1β stimulation. Production of NO, PGE2, TNF-α and IL-6 were evaluated by the Griess reaction and ELISAs. The mRNA (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, Sox-9, aggrecan and collagen-II) and protein expression (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5 and SIRT1) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and SIRT1. SIRT1 activity was quantified with SIRT1 fluorometric assay kit. The in vivo effect of fisetin was evaluated by gavage in mice OA models induced by destabilization of the medial meniscus (DMM). We found that fisetin inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5. Besides, fisetin remarkably decreased IL-1β-induced degradation of Sox-9, aggrecan and collagen-II. Furthermore, fisetin significantly inhibited IL-1β-induced SIRT1 decrease and inactivation. However, the inhibitory effect of fisetin was obvious abolished by sirtinol, suggesting that fisetin exerts anti-inflammatory effects through activating SIRT1. In vivo, fisetin-treated mice exhibited less cartilage destruction and lower OARSI scores. Moreover, fisetin reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that fisetin may be a potential agent in the treatment of OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/β-Catenin Pathway

    Directory of Open Access Journals (Sweden)

    Sara Cheleschi

    2017-01-01

    Full Text Available Mechanical loading and hydrostatic pressure (HP regulate chondrocytes’ metabolism; however, how mechanical stimulation acts remain unclear. MicroRNAs (miRNAs play an important role in cartilage homeostasis, mechanotransduction, and in the pathogenesis of osteoarthritis (OA. This study investigated the effects of a cyclic HP (1–5 MPa, in both normal and OA human chondrocytes, on the expression of miR-27a/b, miR-140, miR-146a/b, and miR-365, and of their target genes (MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4. Furthermore, we assessed the possible involvement of Wnt/β-catenin pathway in response to HP. Chondrocytes were exposed to HP for 3h and the evaluations were performed immediately after pressurization, and following 12, 24, and 48 h. Total RNA was extracted and used for real-time PCR. β-catenin was detected by Western blotting analysis and immunofluorescence. In OA chondrocytes, HP induced a significant increase (p < 0.01 of the expression levels of miR-27a/b, miR-140, and miR-146a, and a significant reduction (p < 0.01 of miR-365 at all analyzed time points. MMP-13, ADAMTS-5, and HDAC-4 were significantly downregulated following HP, while no significant modification was found for IGFBP-5. β-catenin levels were significantly increased (p < 0.001 in OA chondrocytes at basal conditions and significantly reduced (p < 0.01 by HP. Pressurization did not cause any significant modification in normal cells. In conclusion, in OA chondrocytes, HP restores the expression levels of some miRNAs, downregulates MMP-13, ADAMTS-5, and HDAC-4, and modulates the Wnt/β-catenin pathway activation.

  7. Community-Acquired Acute Kidney Injury: A Nationwide Survey in China.

    Science.gov (United States)

    Wang, Yafang; Wang, Jinwei; Su, Tao; Qu, Zhen; Zhao, Minghui; Yang, Li

    2017-05-01

    This study aimed to describe the burden of community-acquired acute kidney injury (AKI) in China based on a nationwide survey about AKI. Cross-sectional and retrospective study. A national sample of 2,223,230 hospitalized adult patients from 44 academic/local hospitals in Mainland China was used. AKI was defined according to the 2012 KDIGO AKI creatinine criteria or an increase or decrease in serum creatinine level of 50% during the hospital stay. Community-acquired AKI was identified when a patient had AKI that could be defined at hospital admission. The rate, cause, recognition, and treatment of community-acquired AKI were stratified according to hospital type, latitude, and economic development of the regions in which the patients were admitted. All-cause in-hospital mortality and recovery of kidney function at hospital discharge. 4,136 patients with community-acquired AKI were identified during the 2 single-month snapshots (January 2013 and July 2013). Of these, 2,020 (48.8%) had cases related to decreased kidney perfusion; 1,111 (26.9%), to intrinsic kidney disease; and 499 (12.1%), to urinary tract obstruction. In the north versus the south, more patients were exposed to nephrotoxins or had urinary tract obstructions. 536 (13.0%) patients with community-acquired AKI had indications for renal replacement therapy (RRT), but only 347 (64.7%) of them received RRT. Rates of timely diagnosis and appropriate use of RRT were higher in regions with higher per capita gross domestic product. All-cause in-hospital mortality was 7.3% (295 of 4,068). Delayed AKI recognition and being located in northern China were independent risk factors for in-hospital mortality, and referral to nephrology providers was an independent protective factor. Possible misclassification of AKI and community-acquired AKI due to nonstandard definitions and missing data for serum creatinine. The features of community-acquired AKI varied substantially in different regions of China and were closely

  8. Validation of the Infectious Diseases Society of America/American Thoracic Society criteria to predict severe community-acquired pneumonia caused by Streptococcus pneumoniae.

    Science.gov (United States)

    Kontou, Paschalina; Kuti, Joseph L; Nicolau, David P

    2009-10-01

    Severe community-acquired pneumonia (CAP) is usually defined as pneumonia that requires intensive care unit (ICU) admission; the primary pathogen responsible for ICU admission is Streptococcus pneumoniae. In this study, the 2007 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) consensus criteria for ICU admission were compared with other severity scores in predicting ICU admission and mortality. We retrospectively studied 158 patients with pneumococcal CAP (1999-2003). Clinical and laboratory features at the emergency department were recorded and used to calculate the 2007 IDSA/ATS rule, the 2001 ATS rule, 2 modified 2007 IDSA/ATS rules, the Pneumonia Severity Index (PSI), and the CURB (confusion, urea, respiratory rate, blood pressure) score. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were assessed for the various indices. We also determined the criteria that were independently predictive of ICU admission and of mortality in our population. The 2007 IDSA/ATS criteria performed as well as the 2001 ATS rule in predicting ICU admission both demonstrated high sensitivity (90%) and NPV (97%). For the prediction of mortality, the best tool proved to be the PSI score (sensitivity, 95%; NPV, 99%). The variables associated with ICU admission in this patient population included tachypnea, confusion, Pao(2)/Fio(2) ratio of 250 or lower, and hypotension requiring fluid resuscitation. Mechanical ventilation and PSI class V were independently associated with mortality. This study confirms the usefulness of the new criteria in predicting severe CAP. The 2001 ATS criteria seem an attractive alternative because they are simple and as effective as the 2007 IDSA/ATS criteria.

  9. Severe hypertriglyceridemia in Japan: Differences in causes and therapeutic responses.

    Science.gov (United States)

    Murase, Toshio; Okubo, Minoru; Ebara, Tetsu; Mori, Yasumichi

    Severe hypertriglyceridemia (>1000 mg/dL) has a variety of causes and frequently leads to life-threating acute pancreatitis. However, the origins of this disorder are unclear for many patients. We aimed to characterize the causes of and responses to therapy in rare cases of severe hypertriglyceridemia in a group of Japanese patients. We enrolled 121 patients from a series of case studies that spanned 30 years. Subjects were divided into 3 groups: (1) primary (genetic causes); (2) secondary (acquired); and (3) disorders of uncertain causes. In the last group, we focused on 3 possible risks factors for hypertriglyceridemia: obesity, diabetes mellitus, and heavy alcohol intake. Group A (n = 20) included 13 patients with familial lipoprotein lipase deficiency, 3 patients with apolipoprotein CII deficiency, and other genetic disorders in the rest of the group. Group B patients (n = 15) had various metabolic and endocrine diseases. In Group C (uncertain causes; n = 86), there was conspicuous gender imbalance (79 males, 3 females) and most male subjects were heavy alcohol drinkers. In addition, 18 of 105 adult patients (17%) had histories of acute pancreatitis. The cause of severe hypertriglyceridemia is uncertain in many patients. In primary genetic forms of severe hypertriglyceridemia, genetic diversity between populations is unknown. In the acquired forms, we found fewer cases of estrogen-induced hypertriglyceridemia than in Western countries. In our clinical experience, the cause of most hypertriglyceridemia is uncertain. Our work suggests that genetic factors for plasma triglyceride sensitivity to alcohol should be explored. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Parenting and psychiatric rehabilitation: Can parents with severe mental illness benefit from a new approach? : 1-3 October

    NARCIS (Netherlands)

    Joanne Nicholson; dr. P.C. van der Ende; Jaap van Weeghel; Dr. Lies Korevaar; Jooske T. van Busschbach

    2015-01-01

    Can parents with severe mental illness benefit from a new approach? XIthENMESH International Conference in Málaga (Spain). 1-3 October, 2015. With these results at hand we developed a new program and evaluated it . In this presentation we will reflect on the merits of this program but also share

  11. [Ceftaroline fosamil in community-acquired and nosocomial pneumonia].

    Science.gov (United States)

    Calbo, Esther; Zaragoza, Rafael

    2014-03-01

    Community-acquired pneumonia (CAP) is a common infection in developed countries and causes a large number of hospital admissions and deaths. In recent years, the incidence of this disease has increased, caused by progressive population aging. Following the introduction of the conjugate vaccine against Streptococcus pneumoniae, there have been significant epidemiological changes that require close monitoring because of the possible emergence of new patterns of resistance. This article aims to review the role of ceftaroline fosamil, a new parenteral cephalosporin with antibacterial activity against Gram-negative and Gram-positive pathogens, in the treatment of pneumonia. Several in vitro and in vivo studies have shown the efficacy of ceftaroline fosamil against penicillin-resistant S. pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). Additionally, ceftaroline has shown similar efficacy and safety to ceftriaxone in the treatment of community-acquired pneumonia with severe prognosis (prognostic severity index III and IV) in two phase III clinical trials. Although a non-inferiority design was used for these clinical trials, some data suggest a superior efficacy of ceftaroline, with earlier clinical response and higher cure rate in infections caused by S. pneumoniae, making this drug particularly interesting for critically-ill patients admitted to the intensive care unit. Ceftaroline may also be considered for empirical and directed treatment of MRSA pneumonia. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  12. Acquired Credit Unions: Drivers of Takeover

    Directory of Open Access Journals (Sweden)

    R. Raymond Sant

    2015-08-01

    Full Text Available In this paper we study acquired credit unions and analyze their financial performance up to six years prior to merger, on a quarterly basis. The primary focus is on balance sheet (asset liability management and profitability variables (return on assets. We find that acquired credit unions during the period 2008 (third quarter to 2014 (first quarter experienced negative return on assets for several quarters prior to their takeover. This was the result of a declining loan portfolio and increasing charge offs. In spite of decreasing lending activity, such credit unions continued to increase their deposits, i.e., adding to their cost base. Due to declining loans, their net interest margin as a proportion of deposits was also in decline. We argue that this is an indicator of poor management ability. Furthermore, our analysis finds that operating expenses were increasing over time, something that has been documented in previous literature also for smaller credit unions and is attributable to lack of economies of scale. The average asset size of the acquired credit unions in our sample is about $22 million just before acquisition. We attribute our findings to poor business strategy followed by such credit unions. We also conclude that signs of trouble are evident up to two years before merger on average and regulatory policy may have to become more proactive to manage the consolidation challenge faced by the credit union industry in general.

  13. Response actions to difficulties in using everyday technology after acquired brain injury.

    Science.gov (United States)

    Larsson Lund, Maria; Lövgren Engström, Ann-Louice; Lexell, Jan

    2012-03-01

    People with acquired brain injury (ABI) have difficulties using everyday technology (ET) in daily tasks at home and in society. To support them in managing the demands imposed by using ET, knowledge is needed concerning their response actions to the difficulties. The aim of this study was to explore and describe what characterizes response actions to difficulties using ET, their conditions, and how they influence the experiences of tasks in daily life among people with ABI. Interviews and observations were undertaken with 13 persons with an ABI. Data were analysed qualitatively using the constant comparative method. The participants' response actions were categorized as (i) deliberate and organized planning, (ii) random and inflexible repeating (iii), re-evaluating tasks, (iv) explaining difficulties related to others, and (iv) proving and protecting capability. Certain conditions were decisive for the different response actions to be applied and also for their effectiveness in enabling engagement in tasks in daily life. Each participant used several types of response actions and the same action could be applied in several situations. To support people with an ABI to manage the demands imposed by using ET, it is important to identify the uniqueness of each client and his or her response actions to difficulties using ET and thereafter adjust the interventions accordingly.

  14. Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

    Directory of Open Access Journals (Sweden)

    Marlene Pereira Garanito

    2014-09-01

    Full Text Available Objective: To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. Methods: Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. Results: The overall response rate at six months was 34.6% (9/26, and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66% at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7% at five years with both clonal evolutions in non -responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%. Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States. Resumo: Objetivo: Avaliar o resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina como tratamento inicial em nosso instituto. Métodos: Análise retrospectiva de 26 pacientes pediátricos com anemia aplástica tratados entre 1996 e 2011 com globulina antitimocítica de coelho e ciclosporina. Resultados: A taxa de resposta geral em seis meses foi de 34,6% (9/26, e a incidência acumulada de recorrência foi de 26,5% (intervalo de confiança [IC] de 95%,1,4%-66% em cinco anos. A incidência acumulada de evolução clonal após a terapia imunossupressora foi de 8,3% (IC 95%, 0,001%-53,7% em cinco anos, com ambas as evoluções clonais em pacientes sem resposta que adquiriram o cariótipo com monossomia 7. A sobrevida geral em cinco anos foi de 73,6% (IC 95%, 49

  15. Visual rehabilitation with Retimax Vision Trainer in patients with severe Acquired Brain Injury: report of two cases

    Directory of Open Access Journals (Sweden)

    Margherita Chiari

    2014-04-01

    Full Text Available Retimax Vision Trainer is a device that has the purpose to improve visual function by means of the detection of a visual evoked potential associated with a sound feedback. We evaluated the effectiveness of rehabilitative treatment in two patients with Acquired Brain Injury (ABI. Results, subjectively appreciated, are objectively confirmed by the improvement of visual function.

  16. Mechanical property and conductivity changes in several copper alloys after 13.5 dpa neutron irradiation

    International Nuclear Information System (INIS)

    Ames, M.; Kohse, G.; Lee, T.S.; Grant, N.J.; Harling, O.K.

    1986-01-01

    A scoping experiment in which 25 different copper materials of 17 alloy compositions were irradiated to approx.13.5 dpa approx.400 0 C in a fast reactor is described. The materials include rapidly solidified (RS) alloys, with and without oxide dispersion strengthening, as well as conventionally processed alloys. Immersion density (swelling), electrical conductivity (which can be related to thermal conductivity), and yield stress and ductility by miniature disk bend testing have been measured before and after irradiation. It was found, in general, that the Rs alloys are stable under irradiation to 13.5 dpa, showing small conductivity changes and little or no swelling. Reduction of strength and ductility, in post-irradiation tests at the irradiation temperature, are not generally observed. Some conventionally processed alloys also performed well, although irradiation softening and swelling of several percent were observed in some cases, and pure copper swelled in excess of 5%. It is concluded that a number of copper alloys should receive further study, and that higher dose irradiations will be required to establish the limits of swelling suppression in these alloys

  17. Behavior Management for Children and Adolescents with Acquired Brain Injury

    Science.gov (United States)

    Slifer, Keith J.; Amari, Adrianna

    2009-01-01

    Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have…

  18. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China.

    Science.gov (United States)

    Yang, Jun; Li, Lin-Fa; Xu, Qin; Zhang, Jun; Weng, Wan-Wen; Zhu, Yang-Jun; Dong, Meng-Jie

    2015-03-01

    Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

  19. Severe Tricuspid Regurgitation Diagnosed 13 Years after a Car Accident: A Case Report

    Science.gov (United States)

    Acar, Burak; Suleymanoglu, Muhammed; Burak, Cengiz; Demirkan, Burcu Mecit; Guray, Yesim; Tufekcioglu, Omac; Aydogdu, Sinan

    2015-01-01

    Abstract Blunt chest traumas mostly occur due to car accidents and can cause many cardiac complications such as septal rupture, free-wall rupture, coronary artery dissection or thrombosis, heart failure, arrhythmias, and chordae and papillary muscle rupture. One of the most serious complication is tricuspid regurgitation (TR), which can be simply diagnosed by physical examination and confirmed by echocardiography. We describe a 48-year-old female patient, diagnosed with severe TR 13 years after a blunt chest trauma due to a car accident. TR was diagnosed with transthoracic echocardiography and three dimensional transthoracic echocardiography had defined the exact pathology of the tricuspid valve. The patient underwent successful surgery with bioprosthetic valve implantation and was discharged at 6th postoperative day without any complication. The patient had no problem according to the follow-up one month and six months after operation. PMID:26157464

  20. Cerebral involvement in acquired immunodeficiency syndrome (AIDS)

    International Nuclear Information System (INIS)

    Krestin, G.P.; Juergens, R.; Steinbrich, W.; Diederich, N.; Koeln Univ.

    1986-01-01

    Involvement of the central nervous system in acquired immune deficiency syndrome (AIDS) is usually due to opportunistic infections; these frequently offer a difficult differential diagnostic problem. Imaging methods play an important part in the elucidation of symptoms. CT and MR findings were analysed in 13 patients with AIDS and neurological symptoms. Some infections of the central nervous system (encephalitis of unknown aetiology, cytomegalic encephalitis, meningitis) may show cerebral atrophy or even no morphological changes. Toxoplasmosis and PML are the most common opportunistic infections typical changes on CT and MR may lead to diagnosis. MR offers advantages compared with CT in its higher sensitivity for the demonstration even of small lesions. (orig.) [de

  1. 13 CFR 107.50 - Definition of terms.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Definition of terms. 107.50 Section 107.50 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT... acquired business satisfies paragraphs (1) and (2) of this definition. Temporary Debt has the meaning set...

  2. Community-Acquired Pneumonia: a Comparison between elderly and nonelderly patients

    Directory of Open Access Journals (Sweden)

    S. Jafari

    2006-08-01

    Full Text Available Background: Community-acquired pneumonia could be a life-threatening condition especially in elderly patients. The factors influencing the outcome in elderly patients are thought to be different from those in young adults. We compared the clinical and paraclinical profiles in elderly and nonelderly patients with community-acquired pneumonias. Methods: In this cross-sectional study, seventy nine patients who were hospitalized with community acquired pneumonia over a period of one year were included. Patients' medical records were reviewed; and data related to comorbid conditions, signs and symptoms, laboratory and radiographic findings were gathered using a checklist. Results: The clinical features, laboratory parameters and complications from pneumonia were almost similar in 41 elderly (group I, age ≥65years and 38 young (group II, age<65years subjects. Delirium was seen more in elderly group (p=0.05. The average body temperature and pulse rate were significantly higher in nonelderly group. Sixty one percent of elderly patients and 21% of young patients have Po2 less than 60 (p=0.02. Smoking (29.1%, neurological disturbances (19%, congestive heart failure (15.2%, chronic obstructive pulmonary disease and diabetes mellitus (13.9% were associated comorbidities in both groups. In non elderly group, immune compromise and IV drug use were more common as underlying comorbid conditions. Two of three mortalities were due to elder patients. Conclusion: Community acquired pneumonia could have more serious clinical and abnormal laboratory features in the elderly than younger patients. Mortality rate may be higher in older patients. Comorbid conditions are frequently seen in both elderly and nonelderly patients with community acquired pneumonia, but IV drug use and immune compromise are more frequent in nonelderly patients.

  3. Severe community-acquired Enterobacter pneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia

    Science.gov (United States)

    2011-01-01

    Background Patients with Enterobacter community-acquired pneumonia (EnCAP) were admitted to our intensive care unit (ICU). Our primary aim was to describe them as few data are available on EnCAP. A comparison with CAP due to common and typical bacteria was performed. Methods Baseline clinical, biological and radiographic characteristics, criteria for health-care-associated pneumonia (HCAP) were compared between each case of EnCAP and thirty age-matched typical CAP cases. A univariate and multivariate logistic regression analysis was performed to determine factors independently associated with ENCAP. Their outcome was also compared. Results In comparison with CAP due to common bacteria, a lower leukocytosis and constant HCAP criteria were associated with EnCAP. Empiric antibiotic therapy was less effective in EnCAP (20%) than in typical CAP (97%) (p < 0.01). A delay in the initiation of appropriate antibiotic therapy (3.3 ± 1.6 vs. 1.2 ± 0.6 days; p < 0.01) and an increase in duration of mechanical ventilation (8.4 ± 5.2 vs. 4.0 ± 4.3 days; p = 0.01) and ICU stay were observed in EnCAP patients. Conclusions EnCAP is a severe infection which is more consistent with HCAP than with typical CAP. This retrospectively suggests that the application of HCAP guidelines should have improved EnCAP management. PMID:21569334

  4. Identification and Severity Determination of Wheat Stripe Rust and Wheat Leaf Rust Based on Hyperspectral Data Acquired Using a Black-Paper-Based Measuring Method

    Science.gov (United States)

    Ruan, Liu; Wang, Rui; Liu, Qi; Ma, Zhanhong; Li, Xiaolong; Cheng, Pei; Wang, Haiguang

    2016-01-01

    It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R2) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies. PMID:27128464

  5. Identification and Severity Determination of Wheat Stripe Rust and Wheat Leaf Rust Based on Hyperspectral Data Acquired Using a Black-Paper-Based Measuring Method.

    Science.gov (United States)

    Wang, Hui; Qin, Feng; Ruan, Liu; Wang, Rui; Liu, Qi; Ma, Zhanhong; Li, Xiaolong; Cheng, Pei; Wang, Haiguang

    2016-01-01

    It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R2) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies.

  6. Post-injury personality in the prediction of outcome following severe acquired brain injury.

    Science.gov (United States)

    Cattran, Charlotte Jane; Oddy, Michael; Wood, Rodger Llewellyn; Moir, Jane Frances

    2011-01-01

    The aim of the study was to examine the utility of five measures of non-cognitive neurobehavioural (NCNB) changes that often occur following acquired brain injury, in predicting outcome (measured in terms of participation and social adaptation) at 1-year follow-up. The study employed a longitudinal, correlational design. Multiple regression was employed to investigate the value of five new NCNB measures of social perception, emotional regulation, motivation, impulsivity and disinhibition in the prediction of outcome as measured by the Mayo-Portland Adaptability Inventory (MPAI). Two NCNB measures (motivation and emotional regulation) were found to significantly predict outcome at 1-year follow-up, accounting for 53% of the variance in MPAI total scores. These measures provide a method of quantifying the extent of NCNB changes following brain injury. The predictive value of the measures indicates that they may represent a useful tool which could aid clinicians in identifying early-on those whose symptoms are likely to persist and who may require ongoing intervention. This could facilitate the planning of rehabilitation programmes.

  7. Community-acquired bacterial meningitis

    NARCIS (Netherlands)

    van de Beek, Diederik; Brouwer, Matthijs; Hasbun, Rodrigo; Koedel, Uwe; Whitney, Cynthia G.; Wijdicks, Eelco

    2016-01-01

    Meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. It can be acquired spontaneously in the community - community-acquired bacterial meningitis - or in the hospital as a complication of invasive procedures or head trauma

  8. Acquired Methemoglobinaemia

    Directory of Open Access Journals (Sweden)

    Adil Al-Lawati

    2012-05-01

    Full Text Available Acquired methemoglobinaemia is a relatively rare condition and, therefore infrequently encountered in acute medical practice. Suspicion of the condition may be triggered when the measured PaO2 is ‘out of keeping’ with the oxygen saturations that are discovered with pulse oximetry. We describe two separate cases of acquired methemoglobinaemia secondary to the recreational use of alkyl nitrites (’poppers’. The patients presented at separate times to two different teaching hospitals in London, UK. The similarity of these cases has led the authors to conclude that a raised awareness of this potentially fatal condition, and its association with a widely-available recreational drug, is necessary to ensure a correct and timely diagnosis.

  9. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  10. Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

    Science.gov (United States)

    Agrawal, Swati; Townley, Robert G

    2014-02-01

    Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

  11. Community-Acquired Pneumonia Visualized on CT Scans but Not Chest Radiographs: Pathogens, Severity, and Clinical Outcomes.

    Science.gov (United States)

    Upchurch, Cameron P; Grijalva, Carlos G; Wunderink, Richard G; Williams, Derek J; Waterer, Grant W; Anderson, Evan J; Zhu, Yuwei; Hart, Eric M; Carroll, Frank; Bramley, Anna M; Jain, Seema; Edwards, Kathryn M; Self, Wesley H

    2018-03-01

    The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain. In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data. The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%). Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography. Copyright © 2017 American College of Chest Physicians. All rights reserved.

  12. The role of electron localization in the atomic structure of transition-metal 13-atom clusters: the example of Co13, Rh13, and Hf13.

    Science.gov (United States)

    Piotrowski, Maurício J; Piquini, Paulo; Cândido, Ladir; Da Silva, Juarez L F

    2011-10-14

    The crystalline structure of transition-metals (TM) has been widely known for several decades, however, our knowledge on the atomic structure of TM clusters is still far from satisfactory, which compromises an atomistic understanding of the reactivity of TM clusters. For example, almost all density functional theory (DFT) calculations for TM clusters have been based on local (local density approximation--LDA) and semilocal (generalized gradient approximation--GGA) exchange-correlation functionals, however, it is well known that plain DFT fails to correct the self-interaction error, which affects the properties of several systems. To improve our basic understanding of the atomic and electronic properties of TM clusters, we report a DFT study within two nonlocal functionals, namely, the hybrid HSE (Heyd, Scuseria, and Ernzerhof) and GGA+U functionals, of the structural and electronic properties of the Co(13), Rh(13), and Hf(13) clusters. For Co(13) and Rh(13), we found that improved exchange-correlation functionals decrease the stability of open structures such as the hexagonal bilayer (HBL) and double simple-cubic (DSC) compared with the compact icosahedron (ICO) structure, however, DFT-GGA, DFT-GGA+U, and DFT-HSE yield very similar results for Hf(13). Thus, our results suggest that the DSC structure obtained by several plain DFT calculations for Rh(13) can be improved by the use of improved functionals. Using the sd hybridization analysis, we found that a strong hybridization favors compact structures, and hence, a correct description of the sd hybridization is crucial for the relative energy stability. For example, the sd hybridization decreases for HBL and DSC and increases for ICO in the case of Co(13) and Rh(13), while for Hf(13), the sd hybridization decreases for all configurations, and hence, it does not affect the relative stability among open and compact configurations.

  13. Expression of matrix metalloproteinase genes during basement membrane degradation in the metamorphosis of Bombyx mori.

    Science.gov (United States)

    Kawasaki, Hideki; Manickam, Asaithambi; Shahin, Rima; Ote, Manabu; Iwanaga, Masashi

    2018-01-05

    The present study was conducted to clarify the involvement of the basement membrane (BM) in insect metamorphosis through analysis of the expression profile of two types of metalloproteinase (MMP and ADAMTS) genes in several organs, their ecdysone involvement, and the histological change of BM. BM was observed around wing sac and in the wing cavity and around fat bodies at the W0 stage but disappeared after the W3 stage, and wing discs evaginated and fat body cells scattered after the W3 stage. The disappearance of the BM of midgut and silk glands was not observed after the W3 stage, but degenerated epithelium cells in the midgut and shrunken cells in the silk gland were observed after the W3 stage. BmMMP1 showed a peak at P0 in the wing discs, fat bodies, midgut, and silk gland. BmMMP2 showed a broad peak around pupation in the wing discs, fat bodies, midgut, and silk gland. BmADAMTS-1 showed enhanced expression at W2 in the wing discs, fat bodies, midgut, and hemocyte, while BmADAMTS-L showed enhanced expression at W3 in the fat bodies, midgut, silk gland, and hemocyte. After pupation, they showed a different expression in different organs. All of four genes were induced by 20-hydroxyecdysone in wing discs in vitro. The present results suggested the involvement of MMPs and ADAMTS in the BM digestion and the morphogenesis of organs during Bombyx metamorphosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Sigmoid plate dehiscence: Congenital or acquired condition?

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhaohui, E-mail: lzhtrhos@163.com [Capital Medical University, Beijing Tongren Hospital, No 1 Dong Jiao Min Street, Dongcheng District, Beijing 100730 (China); Li, Jing, E-mail: lijingxbh@yahoo.com.cn [Capital Medical University, Beijing Tongren Hospital, No 1 Dong Jiao Min Street, Dongcheng District, Beijing 100730 (China); Zhao, Pengfei, E-mail: zhaopengf05@163.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Lv, Han, E-mail: chrislvhan@126.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Dong, Cheng, E-mail: derc007@sina.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Liu, Wenjuan, E-mail: wenjuanliu@163.com [Jining No. 1 People' s Hospital, No. 6 Health Street, Jining 272100 (China); Wang, Zhenchang, E-mail: cjr.wzhch@vip.163.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China)

    2015-05-15

    Highlights: • CT with multiplanar reformations can accurately display the sigmoid platet dehiscence. • The prevalence of sigmoid plate dehiscence was no significant difference among different age groups. • The size of sigmoid plate bony defects were not statistically different among different age groups. • The sigmoid plate dehiscence is more commonly a congenital than an acquired condition. - Abstract: Background and purpose: The imaging features of sigmoid plate dehiscence-induced pulsatile tinnitus have been presented. The origin of the sigmoid plate dehiscence, however, remains unclear. Our aim was to assess the prevalence and extent of sigmoid plate dehiscence on computed tomography (CT) images in multiple age groups to determine whether this condition is more likely to be congenital or acquired. Materials and methods: We retrospectively reviewed contrast-enhanced CT images of sigmoid plates of temporal bones in 504 patients. Each temporal bone was characterized as normal or dehiscent. Patients were then subcategorized into four age groups, and the prevalence and extent of dehiscent sigmoid plates in each group were calculated and compared. Results: Overall, 80 patients had sigmoid plate dehiscence, nine of whom had it bilaterally. In successively older age groups, the prevalences of sigmoid plate dehiscence were 18.9%, 20.1%, 14.5%, and 12.7%, respectively. Respective average anteroposterior bony defect diameters were 3.7 ± 1.7, 3.0 ± 1.3, 3.1 ± 1.5, and 3.0 ± 1.1 mm. Respective average vertical bony defect diameters were 3.6 ± 2.3, 2.6 ± 1.2, 3.2 ± 1.5, and 3.0 ± 1.7 mm. The prevalence and extent of sigmoid plate dehiscence were not statistically different among the four age groups. Conclusions: The similar radiologic prevalence and extent of dehiscent sigmoid plates among the age groups suggest that the dehiscence is more commonly a congenital than an acquired condition.

  15. Sigmoid plate dehiscence: Congenital or acquired condition?

    International Nuclear Information System (INIS)

    Liu, Zhaohui; Li, Jing; Zhao, Pengfei; Lv, Han; Dong, Cheng; Liu, Wenjuan; Wang, Zhenchang

    2015-01-01

    Highlights: • CT with multiplanar reformations can accurately display the sigmoid platet dehiscence. • The prevalence of sigmoid plate dehiscence was no significant difference among different age groups. • The size of sigmoid plate bony defects were not statistically different among different age groups. • The sigmoid plate dehiscence is more commonly a congenital than an acquired condition. - Abstract: Background and purpose: The imaging features of sigmoid plate dehiscence-induced pulsatile tinnitus have been presented. The origin of the sigmoid plate dehiscence, however, remains unclear. Our aim was to assess the prevalence and extent of sigmoid plate dehiscence on computed tomography (CT) images in multiple age groups to determine whether this condition is more likely to be congenital or acquired. Materials and methods: We retrospectively reviewed contrast-enhanced CT images of sigmoid plates of temporal bones in 504 patients. Each temporal bone was characterized as normal or dehiscent. Patients were then subcategorized into four age groups, and the prevalence and extent of dehiscent sigmoid plates in each group were calculated and compared. Results: Overall, 80 patients had sigmoid plate dehiscence, nine of whom had it bilaterally. In successively older age groups, the prevalences of sigmoid plate dehiscence were 18.9%, 20.1%, 14.5%, and 12.7%, respectively. Respective average anteroposterior bony defect diameters were 3.7 ± 1.7, 3.0 ± 1.3, 3.1 ± 1.5, and 3.0 ± 1.1 mm. Respective average vertical bony defect diameters were 3.6 ± 2.3, 2.6 ± 1.2, 3.2 ± 1.5, and 3.0 ± 1.7 mm. The prevalence and extent of sigmoid plate dehiscence were not statistically different among the four age groups. Conclusions: The similar radiologic prevalence and extent of dehiscent sigmoid plates among the age groups suggest that the dehiscence is more commonly a congenital than an acquired condition

  16. Hospital-acquired pneumonia is an independent predictor of poor global outcome in severe traumatic brain injury up to 5 years after discharge.

    Science.gov (United States)

    Kesinger, Matthew Ryan; Kumar, Raj G; Wagner, Amy K; Puyana, Juan Carlos; Peitzman, Andrew P; Billiar, Timothy R; Sperry, Jason L

    2015-02-01

    Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Limited information exists regarding the significance of infectious complications on long-term outcomes after TBI. We sought to characterize risks associated with HAP on outcomes 5 years after TBI. This study involved data from the merger of an institutional trauma registry and the Traumatic Brain Injury Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale [AIS] score ≥ 4) who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scale-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into low (GOSE score GOSE score ≥ 6). Logistic regression was used to determine adjusted odds of low GOSE score associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS) score, ventilation days, and other important confounders. A general estimating equation model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation. A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS score. Logistic regression demonstrated that HAP was independently associated with low GOSE scores at follow-up (1 year: odds ratio [OR], 6.39; 95% confidence interval [CI], 1.76-23.14; p = 0.005) (2 years: OR, 7.30; 95% CI, 1.87-27.89; p = 0.004) (5-years: OR, 6.89; 95% CI, 1.42-33.39; p = 0.017). Stratifying by GCS score of 8 or lower and early intubation, HAP remained a significant independent predictor of low GOSE score in all strata. In the general estimating equation model, HAP continued to be an independent

  17. Hospital Acquired Pneumonia is an Independent Predictor of Poor Global Outcome in Severe Traumatic Brain Injury up to 5 Years after Discharge

    Science.gov (United States)

    Kesinger, Matthew R.; Kumar, Raj G.; Wagner, Amy K.; Puyana, Juan C.; Peitzman, Andrew P.; Billiar, Timothy R.; Sperry, Jason L.

    2016-01-01

    Objectives Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Little information exists regarding the significance of infectious complications on long-term outcomes post-TBI. We sought to characterize risks associated with HAP on outcomes 5 years post-TBI. Methods Ddata from the merger of an institutional trauma registry and the TBI Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale≥4), who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scaled-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into LOW (GOSEGOSE≥6). Logistic regression was utilized to determine adjusted odds of LOW-GOSE associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS), ventilation days, and other important confounders. A general estimating equation (GEE) model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation. Results A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS. Logistic regression demonstrated that HAP was independently associated with LOW-GOSE scores at follow-up (1year: OR=6.39, 95%CI: 1.76-23.14, p=0.005; 2-years: OR=7.30, 95%CI 1.87-27.89, p=0.004; 5-years: OR=6.89, 95%CI: 1.42-33.39, p=0.017). Stratifying by GCS≤8 and early intubation, HAP remained a significant independent predictor of LOW-GOSE in all strata. In the GEE model, HAP continued to be an independent predictor of LOW-GOSE (OR: 4.59; 95%CI: 1.82-11.60′ p=0.001). Conclusion HAP is independently associated with poor outcomes in severe-TBI extending 5

  18. Multiple myeloma associated with acquired cutis laxa.

    Science.gov (United States)

    Cho, S Y; Maguire, R F

    1980-08-01

    Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

  19. The dynamics of naturally acquired immunity to Plasmodium falciparum infection.

    Directory of Open Access Journals (Sweden)

    Mykola Pinkevych

    Full Text Available Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings. The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well understood. Here we analyse the dynamics of Plasmodium falciparum malaria infection after treatment in a cohort of 197 healthy study participants of different ages in order to model naturally acquired immunity. We find that both delayed time-to-infection and reductions in asymptomatic parasitaemias in older age groups can be explained by immunity that reduces the growth of blood stage as opposed to liver stage parasites. We found that this mechanism would require at least two components - a rapidly acting strain-specific component, as well as a slowly acquired cross-reactive or general immunity to all strains. Analysis and modelling of malaria infection dynamics and naturally acquired immunity with age provides important insights into what mechanisms of immune control may be harnessed by malaria vaccine strategists.

  20. Neurosis of acquired helplessness and role of hypoxia in the formation of this disorder in rats.

    Science.gov (United States)

    Vvedenskaya, O Yu; Avrushchenko, M A; Bol'shakova, T D; Khitrov, N K; Moroz, V V

    2003-04-01

    Acquisition of instrumental defense response with pain reinforcement uncertainty (25% reinforcement) induced the development of acquired helplessness in 50% rats. Acquired helplessness is characterized by the absence of responses to conditioned (light) and unconditioned stimuli (pain), minor response of plasma corticosterone to learning, gas markers of circulatory cerebral hypoxia (Delta A/V pO2 carotid artery/jugular vein), low sensitivity to severe hypobaric conditions, and high resistance of Purkinje cells in the cerebellum. Piracetam improved learning and prevented the development of acquired helplessness. Local changes in cerebral blood flow and energy deficit in neurons responsible for emotional stress during acquired helplessness impair adaptive capacity, but reduce energy consumption and protect neuronal structures.

  1. The association between childhood sexual and physical abuse with incident adult severe obesity across 13 years of the National Longitudinal Study of Adolescent Health

    Science.gov (United States)

    Richardson, Andrea S.; Dietz, William H.; Gordon-Larsen, Penny

    2013-01-01

    Background Severe obesity has increased yet childhood antecedents of adult severe obesity are not well understood. Objective Estimate adult-onset severe obesity risk in individuals with history of childhood physical and/or sexual abuse compared to those who did not report abuse. Methods Longitudinal analysis of participants from the U.S. National Longitudinal Study of Adolescent Health (N=10,774) Wave II (1996; aged 12–22 years) followed through Wave IV (2008–09; aged 24–34 years). New cases of adult-onset severe obesity (BMI≥40 kg/m2 using measured height and weight) in individuals followed over 13 years who were not severely obese during adolescence (BMI childhood was associated with an increased risk of incident severe obesity in adulthood in non-minority females (Hazard Ratio=2.5; 1.3, 4.8) and males (Hazard Ratio=3.6; 1.5, 8.5) compared to individuals with no history of abuse. Conclusion In addition to other social and emotional risks, exposure to sexual and physical abuse during childhood may increase risk of severe obesity later in life. Consideration of the confluence of childhood abuse might be considered as part of preventive and therapeutic approaches to address severe obesity. PMID:24115589

  2. Genomic scan reveals loci under altitude adaptation in Tibetan and Dahe pigs.

    Directory of Open Access Journals (Sweden)

    Kunzhe Dong

    Full Text Available High altitude environments are of particular interest in the studies of local adaptation as well as their implications in physiology and clinical medicine in human. Some Chinese pig breeds, such as Tibetan pig (TBP that is well adapted to the high altitude and Dahe pig (DHP that dwells at the moderate altitude, provide ideal materials to study local adaptation to altitudes. Yet, it is still short of in-depth analysis and understanding of the genetic adaptation to high altitude in the two pig populations. In this study we conducted a genomic scan for selective sweeps using FST to identify genes showing evidence of local adaptations in TBP and DHP, with Wuzhishan pig (WZSP as the low-altitude reference. Totally, we identified 12 specific selective genes (CCBE1, F2RL1, AGGF1, ZFPM2, IL2, FGF5, PLA2G4A, ADAMTS9, NRBF2, JMJD1C, VEGFC and ADAM19 for TBP and six (OGG1, FOXM, FLT3, RTEL1, CRELD1 and RHOG for DHP. In addition, six selective genes (VPS13A, GNA14, GDAP1, PARP8, FGF10 and ADAMTS16 were shared by the two pig breeds. Among these selective genes, three (VEGFC, FGF10 and ADAMTS9 were previously reported to be linked to the local adaptation to high altitudes in pigs, while many others were newly identified by this study. Further bioinformatics analysis demonstrated that majority of these selective signatures have some biological functions relevant to the altitude adaptation, for examples, response to hypoxia, development of blood vessels, DNA repair and several hematological involvements. These results suggest that the local adaptation to high altitude environments is sophisticated, involving numerous genes and multiple biological processes, and the shared selective signatures by the two pig breeds may provide an effective avenue to identify the common adaptive mechanisms to different altitudes.

  3. Molar-incisor hypomineralization: Prevalence, severity and clinical characteristics in 8- to 13-year-old children of Udaipur, India

    OpenAIRE

    Shubha Arehalli Bhaskar; Sapna Hegde

    2014-01-01

    Background: The last couple of decades has seen an increasing interest in molar-incisor hypomineralization (MIH). Although the reported prevalence of MIH ranges from 2.4% to 40.2% worldwide, very little data is available from India. Objective: To assess the prevalence, clinical characteristics, distribution, severity and association with caries of MIH defects in children aged 8-13 years of Udaipur, Rajasthan. Study design: This cross-sectional descriptive study consisted of 1173 children aged...

  4. Arthritis in adults with community-acquired bacterial meningitis: a prospective cohort study

    NARCIS (Netherlands)

    Weisfelt, M.; van de Beek, D.; Spanjaard, L.; de Gans, J.

    2006-01-01

    Background: Although the coexistence of bacterial meningitis and arthritis has been noted in several studies, it remains unclear how often both conditions occur simultaneously. Methods: We evaluated the presence of arthritis in a prospective nationwide cohort of 696 episodes of community-acquired

  5. Brain injury and severe eating difficulties at admission

    DEFF Research Database (Denmark)

    Kjærsgaard, Annette; Kaae Kristensen, Hanne

    Objective: The objective of this pilot study was to explore and interpret the way that individuals with acquired brain injury, admitted to inpatient neurorehabilitation with severe eating difficulties, experienced eating nine to fifteen months after discharge. Methods: Four individuals with acqui......Objective: The objective of this pilot study was to explore and interpret the way that individuals with acquired brain injury, admitted to inpatient neurorehabilitation with severe eating difficulties, experienced eating nine to fifteen months after discharge. Methods: Four individuals...... with acquired brain injury were interviewed via qualitative semi-structured interviews. An explorative study was conducted to study eating difficulties. Qualitative content analysis was used. Results: Four main themes emerged from the analysis: personal values related to eating, swallowing difficulties, eating......-of-life. The preliminary findings provide knowledge regarding the patient perspective of adapting to and developing new strategies for activities related to eating, however, further prospective, longitudinal research in a larger scale and with repeated interviews is needed....

  6. Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood

    DEFF Research Database (Denmark)

    Baumann, Irith; Führer, Monika; Behrendt, Sonja

    2012-01-01

    To evaluate the reproducibility and reliability of the histomorphological criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory cytopenia of childhood (RCC), the most frequently acquired hypocellular bone marrow conditions of childhood.......To evaluate the reproducibility and reliability of the histomorphological criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory cytopenia of childhood (RCC), the most frequently acquired hypocellular bone marrow conditions of childhood....

  7. Community-acquired pneumonia.

    Science.gov (United States)

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  8. Severe Weather Field Experience: An Undergraduate Field Course on Career Enhancement and Severe Convective Storms

    Science.gov (United States)

    Godfrey, Christopher M.; Barrett, Bradford S.; Godfrey, Elaine S.

    2011-01-01

    Undergraduate students acquire a deeper understanding of scientific principles through first-hand experience. To enhance the learning environment for atmospheric science majors, the University of North Carolina at Asheville has developed the severe weather field experience. Participants travel to Tornado Alley in the Great Plains to forecast and…

  9. Why do nonsurvivors from community-acquired pneumonia not receive ventilatory support?

    Science.gov (United States)

    Bauer, Torsten T; Welte, Tobias; Strauss, Richard; Bischoff, Helge; Richter, Klaus; Ewig, Santiago

    2013-08-01

    We investigated rates and predictors of ventilatory support during hospitalization in seemingly not severely compromised nonsurvivors of community-acquired pneumonia (CAP). We used the database from the German nationwide mandatory quality assurance program including all hospitalized patients with CAP from 2007 to 2011. We selected a population not residing in nursing homes, not bedridden, and not referred from another hospital. Predictors of ventilatory support were identified using a multivariate analysis. Overall, 563,901 patients (62.3% of the whole population) were included. Mean age was 69.4 ± 16.6 years; 329,107 (58.4%) were male. Mortality was 39,895 (7.1%). A total of 28,410 (5.0%) received ventilatory support during the hospital course, and 76.3% of nonsurvivors did not receive ventilatory support (62.6% of those aged ventilatory support during hospitalization. Death from CAP occurred significantly earlier in the nonventilated group (8.2 ± 8.9 vs. 13.1 ± 14.1 days; p ventilatory support is disturbingly high, particularly in younger patients. Both performance predictors for not being ventilated remain ambiguous, because they may reflect either treatment restrictions or deficient clinical performance. Elucidating this ambiguity will be part of the forthcoming update of the quality assurance program.

  10. Impact of chronic liver disease in intensive care unit acquired pneumonia: a prospective study.

    Science.gov (United States)

    Di Pasquale, Marta; Esperatti, Mariano; Crisafulli, Ernesto; Ferrer, Miquel; Bassi, Gianluigi Li; Rinaudo, Mariano; Escorsell, Angels; Fernandez, Javier; Mas, Antoni; Blasi, Francesco; Torres, Antoni

    2013-10-01

    To assess the impact of chronic liver disease (CLD) on ICU-acquired pneumonia. This was a prospective, observational study of the characteristics, microbiology, and outcomes of 343 consecutive patients with ICU-acquired pneumonia clustered according to the presence of CLD. Sixty-seven (20%) patients had CLD (67% had liver cirrhosis, LC), MELD score 26 ± 9, 20% Child-Pugh class C). They presented higher severity scores than patients without CLD both on admission to the ICU (APACHE II, LC 19 ± 6 vs. other CLD 18 ± 6 vs. no CLD 16 ± 6; p CLD patients. LC patients had higher 28- and 90-day mortality (63 vs. 28%, p CLD patients. Presence of LC was independently associated with decreased 28- and 90-day survival (95% confidence interval [CI], 1.982-17.250; p = 0.001; 95% confidence interval [CI], 2.915-20.699, p = 0.001, respectively). In critically ill patients with ICU-acquired pneumonia, CLD is associated with a more severe clinical presentation and poor clinical outcomes. Moreover, LC is independently associated with 28- and 90-day mortality. The results of this study are important for future trials focused on mortality.

  11. Independent radiographic prognostic factors in patients with hospital-treated community-acquired pneumonia

    International Nuclear Information System (INIS)

    Wilhelm, K.; Textor, J.; Schild, H.; Ewig, S.; Luederitz, B.; Krollmann, G.

    1999-01-01

    Purpose: To evaluate the independent prognostic impact of the chest radiograph for mortality from community-acquired pneumonia requiring hospitalization. Methods: Chest radiographs of 67 patients with hospital-treated community-acquired pneumonia were analyzed with regard to the prognostic implications of radiographic patterns, extent and density of infiltrates, and its evolution during treatment. Results: Non-survivors had a significantly higher extent of infiltrates (p=0.008), density of infiltrates (p=0.05), and radiographic spread during follow-up within 48-72 hours (p=0.0001). In multivariate analysis, persistent or progressive infiltrates were associated with a 47fold increase, and persistent or progressive density of infiltrates with an 18fold increase in risk of mortality. The presence of both parameters could correctly predict 96% of survivors and 90% of non-survivors. Conclusions: The chest radiograph is an independent predictor of the severity of pneumonia. Both persistent or progressive infiltrates and persistent or progressive density of infiltrates are independently associated with mortality from community-acquired pneumonia. (orig.) [de

  12. Iris recognition: on the segmentation of degraded images acquired in the visible wavelength.

    Science.gov (United States)

    Proença, Hugo

    2010-08-01

    Iris recognition imaging constraints are receiving increasing attention. There are several proposals to develop systems that operate in the visible wavelength and in less constrained environments. These imaging conditions engender acquired noisy artifacts that lead to severely degraded images, making iris segmentation a major issue. Having observed that existing iris segmentation methods tend to fail in these challenging conditions, we present a segmentation method that can handle degraded images acquired in less constrained conditions. We offer the following contributions: 1) to consider the sclera the most easily distinguishable part of the eye in degraded images, 2) to propose a new type of feature that measures the proportion of sclera in each direction and is fundamental in segmenting the iris, and 3) to run the entire procedure in deterministically linear time in respect to the size of the image, making the procedure suitable for real-time applications.

  13. Image Reconstruction. Chapter 13

    Energy Technology Data Exchange (ETDEWEB)

    Nuyts, J. [Department of Nuclear Medicine and Medical Imaging Research Center, Katholieke Universiteit Leuven, Leuven (Belgium); Matej, S. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States)

    2014-12-15

    This chapter discusses how 2‑D or 3‑D images of tracer distribution can be reconstructed from a series of so-called projection images acquired with a gamma camera or a positron emission tomography (PET) system [13.1]. This is often called an ‘inverse problem’. The reconstruction is the inverse of the acquisition. The reconstruction is called an inverse problem because making software to compute the true tracer distribution from the acquired data turns out to be more difficult than the ‘forward’ direction, i.e. making software to simulate the acquisition. There are basically two approaches to image reconstruction: analytical reconstruction and iterative reconstruction. The analytical approach is based on mathematical inversion, yielding efficient, non-iterative reconstruction algorithms. In the iterative approach, the reconstruction problem is reduced to computing a finite number of image values from a finite number of measurements. That simplification enables the use of iterative instead of mathematical inversion. Iterative inversion tends to require more computer power, but it can cope with more complex (and hopefully more accurate) models of the acquisition process.

  14. The ability of clinical and laboratory findings to predict in-hospital death in patients with thrombotic thrombocytopenic purpura in an internal and emergency medicine department

    Directory of Open Access Journals (Sweden)

    Filippo Pieralli

    2012-01-01

    Full Text Available Introduction: Thrombotic thrombocytopenic purpura (TTP is a rare, life-threatening syndrome characterized by microangiopathic anemia, thrombocytopenia, diffuse microvascular thrombosis, and ischemia. It is associated with very low levels of ADAMTS-13. Measurement of ADAMTS-13 levels is used for diagnostic and prognostic purposes, but in every-day clinical practice, this type of analysis is not always readily available. In this retrospective study, we evaluated prognostic value of clinical and laboratory findings in patients with TTP. Materials and methods: We retrospectively investigated patients with clinically diagnosed TTP treated in a unit of Internal and Emergency Medicine (1996-2007. Clinical and laboratory findings were collected and analyzed in order to assess their ability to predict in-hospital death. Results: Twelve patients were identified (mean age 59 + 22 years; 58% were women. Five (42% died during the hospitalization, and the variables significantly associated with this outcome were: a delay between diagnosis and symptom onset (HR 1.36; 95% CI 1.04-1.78; p < 0.05; a higher severity score (HR 1.48; 95%CI 1,23-3.86; p < 0.05; hemodynamic instability with hypotension and/or shock (HR 3.35; 95%CI 3.02-9.26; p < 0.01; a higher schistocyte count on blood smear (HR 1.84; 95%CI 1.04-3.27; p < 0.05; and higher lactate values (HR 1.85; 95%CI 1.08- 3.16; p < 0.05. Conclusions: TTP is a rare and potentially fatal disease with protean manifestations. Delayed diagnosis after symptom onset is a major determinant of poor outcome. Hypotension and shock are also prognostically unfavourable. Laboratory evidence of cardiocirculatory compromise (i.e., elevated lactate levels and extension of the disease process (i.e., schistocyte count > 3 are predictive of in-hospital death, independently of the hemodynamic profile on admission.

  15. 48 CFR 1845.502-70 - Contractor-acquired property.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contractor-acquired... Possession of Contractors 1845.502-70 Contractor-acquired property. All contractor-acquired property must be... contractor-acquired. (2) Submission of DD Form 1419, DOD Industrial Plant Requisition, or equivalent format...

  16. Molar-incisor hypomineralization: Prevalence, severity and clinical characteristics in 8- to 13-year-old children of Udaipur, India

    Directory of Open Access Journals (Sweden)

    Shubha Arehalli Bhaskar

    2014-01-01

    Full Text Available Background: The last couple of decades has seen an increasing interest in molar-incisor hypomineralization (MIH. Although the reported prevalence of MIH ranges from 2.4% to 40.2% worldwide, very little data is available from India. Objective: To assess the prevalence, clinical characteristics, distribution, severity and association with caries of MIH defects in children aged 8-13 years of Udaipur, Rajasthan. Study design: This cross-sectional descriptive study consisted of 1173 children aged 8-13 years selected by random sampling procedure. The European Academy of Pediatric Dentistry criteria were followed for MIH diagnosis. The presence of dental caries and treatment need for MIH-affected teeth were recorded as per the WHO criteria. Results: The prevalence of MIH in the children examined was 9.46%. Severity of the defects increased with the age of the children. Involvement of incisors increased when more First permanent molars (FPMs were affected. An average of 3.65 teeth was involved per MIH-affected individual. Significantly larger numbers of mandibular FPMs and maxillary central incisors were diagnosed with MIH. The association of dental caries was significantly higher with MIH-affected FPMs. Primary molars and permanent canines and premolars were also showed MIH like lesions in some of the MIH-affected children. Conclusion: MIH was observed in about 10% of the children examined. MIH-affected FPMs appear to be more vulnerable to early caries and subsequent pulp involvement with need for extensive dental treatment.

  17. The VCU Pressure Ulcer Summit: Collaboration to Operationalize Hospital-Acquired Pressure Ulcer Prevention Best Practice Recommendations.

    Science.gov (United States)

    Brindle, C Tod; Creehan, Sue; Black, Joyce; Zimmermann, Deb

    2015-01-01

    This executive summary reports outcomes of an interprofessional collaboration between experts in pressure ulcer prevention, bedside clinicians, regulatory agencies, quality improvement, informatics experts, and professional nursing organizations. The goal of the collaboration was to develop a framework to assist facilities to operationalize best practice recommendations to sustain organizational culture change in hospital-acquired pressure ulcer prevention, to develop a hospital-acquired pressure ulcer severity score, and to address topics related to the unavoidable pressure ulcer.

  18. The association between childhood sexual and physical abuse with incident adult severe obesity across 13 years of the National Longitudinal Study of Adolescent Health.

    Science.gov (United States)

    Richardson, A S; Dietz, W H; Gordon-Larsen, P

    2014-10-01

    Severe obesity has increased, yet childhood antecedents of adult severe obesity are not well understood. Estimate adult-onset severe obesity risk in individuals with history of childhood physical and/or sexual abuse compared with those who did not report abuse. Longitudinal analysis of participants from the US National Longitudinal Study of Adolescent Health (n = 10,774) wave II (1996; aged 12-22 years) followed through wave IV (2008-2009; aged 24-34 years). New cases of adult-onset severe obesity (body mass index [BMI] ≥ 40 kg/m2 using measured height and weight) in individuals followed over 13 years who were not severely obese during adolescence (BMI childhood was associated with an increased risk of incident severe obesity in adulthood in non-minority females (hazard ratio [HR; 95% Confidence Interval] = 2.5; 1.3, 4.8) and males (HR = 3.6; 1.5, 8.5) compared with individuals with no history of abuse. In addition to other social and emotional risks, exposure to sexual and physical abuse during childhood may increase risk of severe obesity later in life. Consideration of the confluence of childhood abuse might be considered as part of preventive and therapeutic approaches to address severe obesity. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  19. Acquiring taste in home economics?

    DEFF Research Database (Denmark)

    Stenbak Larsen, Christian

    Objective: To explore how home economics was taught in Denmark before the recent Danish school reform, which also revised the objectives and content of home economics, naming it Food Knowledge (Madkundskab) Methods: Participant observation was done in home economic lessons in two case schools...... appreciated by the group of boys, and others again learned to stick with their idiosyncrasies when pressured by the teacher. Conclusions: Children were acquiring taste in the home economic lessons, but not only the kind of tastes that the teacher had planned for. This leads to reflections on the very complex...... process of taste acquiring and to a call for further research into taste acquiring in complex real life contexts as home economics lessons....

  20. Acquired bleeding disorders

    African Journals Online (AJOL)

    B one marrow aplasia ... Laboratory approach to a suspected acquired bleeding disorder. (LER = leuko- .... lymphocytic leukaemia, and lymphoma). ... cells), a bone marrow aspirate and trephine biopsy (BMAT) is not ..... transplantation.

  1. Thinking Allowed: Use of Egocentric Speech after Acquired Brain Injury (ABI)

    Science.gov (United States)

    Rees, Sian A.; Skidmore, David

    2011-01-01

    This paper explores the use of thinking aloud made by young people who have sustained a severe acquired brain injury (ABI). The phenomenon is compared with the concepts of egocentric speech and inner speech before the form of thinking aloud by pupils with ABI is examined. It is suggested that by using thinking aloud, this group of pupils is able…

  2. Clinical study of serum interleukin-6 in children with community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Ahmed A. Khattab

    2018-06-01

    Full Text Available Background: Community-acquired pneumonia (CAP is an important childhood killer. Excessive production of cytokines, including interleukin-6 (IL-6, might be associated with severe disease course but pediatric data is limited. Aim: To assess value of IL-6 in predicting CAP severity in children. Methods: A prospective study conducted on 73 children hospitalized for CAP and 15 healthy controls. Pneumonia severity was evaluated according to World Health Organization (WHO classification, Respiratory Index of Severity Score (RISC, Predisposition, Insult, Response, Organ dysfunction modified (PIROm score, and Pediatric Respiratory Severity Score (PRESS. Serum IL-6 was measured within 24 h of admission. The primary outcome was occurrence of any pneumonia complications or death within 30 days. Results: IL-6 was significantly higher among patients compared with controls. Unlike CRP, IL-6 was significantly higher among children with severe pneumonia as determined by WHO, PRESS, and RISC (p = 0.001 for all. IL-6 was significantly higher among children with PICU admission, mechanical ventilation, shock (p = 0.001 for all, hypoxia (p < 0.001, and lobar consolidation (p = 0.042. IL-6 had positive correlations with PRESS (rs=0.8, P < 0.001, RISC (rs=0.6, p < 0.001, and PIROm (rs=0.59, p < 0.001 while a negative correlation was found with Oxygen saturation [r = −0.61, p = 0.001]. IL-6 was not significantly correlated with CRP. Receiver Operating Characteristic curve (ROC analysis revealed large area under the curve (AUC of IL-6 for prediction of severe pneumonia as classified by WHO, PRESS, and RISC (AUC = 0.95, 0.94, and 0.89 respectively. Conclusion: IL-6 appears to be valuable for assessment of CAP severity in children compared with conventional biomarkers. Keywords: Interleukin-6, Community acquired pneumonia, C-reactive protein, Prognosis, Pediatric

  3. Chronic obstructive pulmonary disease severity is associated with severe pneumonia

    Directory of Open Access Journals (Sweden)

    Jung Seop Eom

    2015-01-01

    Full Text Available CONTEXT: Chronic obstructive pulmonary disease (COPD is a heterogeneous disorder, and various aspects of COPD may be associated with the severity of pneumonia in such patients. AIMS: We examined the risk factors associated with severe pneumonia in a COPD population. MATERIALS AND METHODS: We performed a retrospective observational study using a prospectively collected database of pneumonia patients who were admitted to our hospital through emergency department between 2008 and 2012. Patients with hospital-acquired pneumonia and those with an immunocompromised status were excluded. RESULTS: Of 148 pneumonia patients with COPD for whom chest computed tomography (CT scans were available, 106 (71.6% and 42 (28.4% were classified as non-severe and severe pneumonia, respectively. Multivariate logistic regression analysis revealed that the severity of airflow limitation [odds ratio (OR, 2.751; 95% confidence interval (CI, 1.074-7.050; P = 0.035] and the presence of emphysema on a chest CT scan (OR, 3.366; 95% CI, 1.104-10.265; P = 0.033 were independently associated with severe pneumonia in patients with COPD. CONCLUSIONS: The severity of COPD including the airflow limitation grade and the presence of pulmonary emphysema were independently associated with the development of severe pneumonia.

  4. Severe aortic valve stenosis and nosebleed

    NARCIS (Netherlands)

    Schoedel, Johannes; Obergfell, Achim; Maass, Alexander H.; Schodel, Johannes

    2007-01-01

    Aortic valve stenosis is known to be associated with loss of high molecular von Willebrand multimers. This can lead to gastrointestinal bleeding in patients with gastrointestinal angiodysplasia, the Heyde syndrome. Here we present a case of anaemia and severe epistaxis associated with acquired von

  5. Acquired pulmonary artery stenosis in four dogs.

    Science.gov (United States)

    Scansen, Brian A; Schober, Karsten E; Bonagura, John D; Smeak, Daniel D

    2008-04-15

    4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.

  6. ISP-31 OECD/NEA/CSNI International Standard Problem n.31. Cora-13 experiment on severe fuel damage. Comparison report

    International Nuclear Information System (INIS)

    Firnhaber, M.; Trambauer, K.; Hagen, S.; Hofmann, P.; Schanz, G.; Sepold, L.

    1993-07-01

    The severe fuel damage experiment CORA-13 has been offered as CSNI-International Standard Problem (ISP) No. 31. The out-of-pile experiment CORA-13 was executed in November 1990 at Kernforschungszentrum Karlsruhe. The major objectives of this experiment were to investigate the behavior of PWR fuel elements during early core degradation and fast cooldown due to refill. Measured quantities are boundary conditions, bundle temperatures, hydrogen generation and the final bundle configuration. The ISP was conducted as a blind exercise. Boundary conditions which could not be measured, but which are necessary for simplified test simulation (axial power profile, shroud insulation temperature, bundle refill flow) were estimated using ATHLET-CD. Results to the ISP were submitted by 9 participants using different versions of SCDAP/RELAP5, and codes such as FRAS-SFD, ICARE2, KESS-III, MELCOR. The thermal behavior up to significant oxidation has been predicted quite well by most of the codes. In general, the capability of the codes in calculating the main degradation phenomena has been clearly illustrated and weaknesses concerning the modelling of some degradation processes have been identified. Among the degradation phenomena involved in the test, the more severe limitations concern the UO 2 -ZrO 2 dissolution by molten Zr, the solubility limits in the resulting U-Zr-O mixture and the cladding failure by the molten mixture

  7. Antibiotics for community-acquired pneumonia in children.

    Science.gov (United States)

    Lodha, Rakesh; Kabra, Sushil K; Pandey, Ravindra M

    2013-06-04

    Pneumonia caused by bacterial pathogens is the leading cause of mortality in children in low-income countries. Early administration of antibiotics improves outcomes. To identify effective antibiotic drug therapies for community-acquired pneumonia (CAP) of varying severity in children by comparing various antibiotics. We searched CENTRAL 2012, Issue 10; MEDLINE (1966 to October week 4, 2012); EMBASE (1990 to November 2012); CINAHL (2009 to November 2012); Web of Science (2009 to November 2012) and LILACS (2009 to November 2012). Randomised controlled trials (RCTs) in children of either sex, comparing at least two antibiotics for CAP within hospital or ambulatory (outpatient) settings. Two review authors independently extracted data from the full articles of selected studies. We included 29 trials, which enrolled 14,188 children, comparing multiple antibiotics. None compared antibiotics with placebo.Assessment of quality of study revealed that 5 out of 29 studies were double-blind and allocation concealment was adequate. Another 12 studies were unblinded but had adequate allocation concealment, classifying them as good quality studies. There was more than one study comparing co-trimoxazole with amoxycillin, oral amoxycillin with injectable penicillin/ampicillin and chloramphenicol with ampicillin/penicillin and studies were of good quality, suggesting the evidence for these comparisons was of high quality compared to other comparisons.In ambulatory settings, for treatment of World Health Organization (WHO) defined non-severe CAP, amoxycillin compared with co-trimoxazole had similar failure rates (odds ratio (OR) 1.18, 95% confidence interval (CI) 0.91 to 1.51) and cure rates (OR 1.03, 95% CI 0.56 to 1.89). Three studies involved 3952 children.In children with severe pneumonia without hypoxaemia, oral antibiotics (amoxycillin/co-trimoxazole) compared with injectable penicillin had similar failure rates (OR 0.84, 95% CI 0.56 to 1.24), hospitalisation rates (OR 1.13, 95

  8. Systolic blood pressure is superior to other haemodynamic predictors of outcome in community acquired pneumonia.

    Science.gov (United States)

    Chalmers, J D; Singanayagam, A; Hill, A T

    2008-08-01

    Admission blood pressure (BP) assessment is a central component of severity assessment for community acquired pneumonia. The aim of this study was to establish which readily available haemodynamic measure on admission is most useful for predicting severity in patients admitted with community acquired pneumonia. A prospective observational study of patients admitted with community acquired pneumonia was conducted in Edinburgh, UK. The measurements compared were systolic and diastolic BP, mean arterial pressure and pulse pressure. The outcomes of interest were 30 day mortality and the requirement for mechanical ventilation and/or inotropic support. Admission systolic BP pressure pressure AUC values for each predictor of 30 day mortality were as follows: systolic BP pressure pressure AUC values for each predictor of need for mechanical ventilation and/or inotropic support were as follows: systolic BP pressure pressure blood pressure AUC 0.76 vs 0.74) and to the standard CURB65 score (0.76 vs 0.76) for the prediction of 30 day mortality. The simplified CRB65 score was equivalent for prediction of mechanical ventilation and/or inotropic support to standard CRB65 (0.77 vs 0.77) and to CURB65 (0.77 vs 0.78). Systolic BP is superior to other haemodynamic predictors of 30 day mortality and need for mechanical ventilation and/or inotropic support in community acquired pneumonia. The CURB65 score can be simplified to a modified CRB65 score by omission of the diastolic BP criterion without compromising its accuracy.

  9. Somatically acquired structural genetic differences

    DEFF Research Database (Denmark)

    Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare

    2016-01-01

    Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34....

  10. 32 CFR 1901.13 - Requirements as to identification of requester.

    Science.gov (United States)

    2010-07-01

    ... INTELLIGENCE AGENCY PUBLIC RIGHTS UNDER THE PRIVACY ACT OF 1974 Filing of Privacy Act Requests § 1901.13... acquired. (c) Requirement for representatives. The parent or guardian of a minor individual, the guardian... provide, in addition to establishing the identity of the minor or individual represented as required in...

  11. Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community acquired pneumonia in children

    International Nuclear Information System (INIS)

    Aurangzeb, B.; Hameed, A.

    2003-01-01

    Objective: To compare the clinical response to amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children and to see the cost effectiveness of each treatment. Subjects and Methods: Patients between 3 to 72 months of age, admitted in the hospital with community acquired pneumonia, were randomly divided into three groups 1,2,3. They were started on amoxicillin, cefuroxime and clarithromycin respectively. The patients were assessed daily. If there was no clinical improvements at 48 hours the antibiotic was changed. ANOVA statistical test was applied to see the clinical response to the treatment in the three groups. Cost effectiveness of the treatment was compared. Results: There was no statistical difference in the clinical response at 48 hours of initiating treatment and discharge (p>0.01 each). The mean hospital stay in group 1 and 2 was 3.3 days and group 3 was 3.2 days respectively (p>0.01). Ninety-seven percent patients in group 1 and 3, and 95% patients in group 2 showed clinical improvement. The cost of treatment of community acquired pneumonia for 8 days was Rs. 496/-, 730/-, 1018/- for amoxicillin, clarithromycin and cefuroxime respectively. Conclusion: Amoxicillin was found in the most cost effective followed by clarithromycin and cefuroxime respectively in the treatment of non-severe and severe community-acquired pneumonia. (author)

  12. Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

    Directory of Open Access Journals (Sweden)

    David Quinto-Alemany

    Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

  13. [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.

  14. Application of unsymmetrical indirect covariance NMR methods to the computation of the (13)C (15)N HSQC-IMPEACH and (13)C (15)N HMBC-IMPEACH correlation spectra.

    Science.gov (United States)

    Martin, Gary E; Hilton, Bruce D; Irish, Patrick A; Blinov, Kirill A; Williams, Antony J

    2007-10-01

    Utilization of long-range (1)H--(15)N heteronuclear chemical shift correlation has continually grown in importance since the first applications were reported in 1995. More recently, indirect covariance NMR methods have been introduced followed by the development of unsymmetrical indirect covariance processing methods. The latter technique has been shown to allow the calculation of hyphenated 2D NMR data matrices from more readily acquired nonhyphenated 2D NMR spectra. We recently reported the use of unsymmetrical indirect covariance processing to combine (1)H--(13)C GHSQC and (1)H--(15)N GHMBC long-range spectra to yield a (13)C--(15)N HSQC-HMBC chemical shift correlation spectrum that could not be acquired in a reasonable period of time without resorting to (15)N-labeled molecules. We now report the unsymmetrical indirect covariance processing of (1)H--(13)C GHMBC and (1)H--(15)N IMPEACH spectra to afford a (13)C--(15)N HMBC-IMPEACH spectrum that has the potential to span as many as six to eight bonds. Correlations for carbon resonances long-range coupled to a protonated carbon in the (1)H--(13)C HMBC spectrum are transferred via the long-range (1)H--(15)N coupling pathway in the (1)H--(15)N IMPEACH spectrum to afford a much broader range of correlation possibilities in the (13)C--(15)N HMBC-IMPEACH correlation spectrum. The indole alkaloid vincamine is used as a model compound to illustrate the application of the method. (c) 2007 John Wiley & Sons, Ltd.

  15. Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark

    DEFF Research Database (Denmark)

    Egelund, Gertrud Baunbæk; Jensen, Andreas Vestergaard; Andersen, Stine Bang

    2017-01-01

    BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin......-G/V was commonly used and not associated with increased mortality in patients with mild to moderate pneumonia. Our results are in agreement with current conservative antibiotic strategy as outlined in the Danish guidelines....

  16. Ability to manage everyday technology after acquired brain injury.

    Science.gov (United States)

    Kassberg, Ann-Charlotte; Malinowsky, Camilla; Jacobsson, Lars; Lund, Maria Larsson

    2013-01-01

    To investigate and describe how persons with an acquired brain injury (ABI) manage everyday technology (ET) in their daily activities and to explore whether the ability to manage ET was related to the severity of the disability. Eighty-one persons with ABI were observed while managing ET by using the Management of Everyday Technology Assessment (META). The Glasgow Outcome Scale-Extended (GOSE) was used to assess the severity of disability after the ABI. A computer application of a Rasch measurement model was used to generate measures of the participants' ability to manage ET and the measures were compared groupwise with analysis of covariance (ANCOVA). The degree of severity of disability had a significant main effect on the ability to manage ET. The groups with severe and moderate disability exhibited a significantly lower ability to manage ET compared to the group with good recovery. The result indicates that the ability to manage ET in daily activities can be related to the global severity of disability after ABI. This demonstrates the importance of considering the ability to manage ET to support the performance of activities at home, at work and in society in persons with ABI.

  17. Thrombotic thrombocytopenic purpura (TTP or Moschowitz syndrome: a true hematologic emergency

    Directory of Open Access Journals (Sweden)

    Deborah Melis

    2012-01-01

    Full Text Available Introduction: Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy caused by congenital or inherited disorders involving the processing of the ultra-large forms of von Willebrand factor. As a result, platelet-rich microthrombi form in the small arterial vessels of various organs, particularly those of the brain, heart, and kidneys. The idiopathic autoimmune form of TTP is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, various disseminated malignancies, and drugs. If not promptly treated, TTP is associated with high mortality, making it a true medical emergency. Materials and methods: The article is based on a review of the literature published between January and October of 2009. Its aim is to clarify the diagnosis, treatment, and follow-up of TTP. Results: Diagnostic criteria include the presence of microangiopathic hemolytic anemia associated with thrombocytopenia in the absence of other obvious causes. Assays of ADAMTS13 activity and titration of acquired antibodies against this enzyme are indicated in the follow-up of disease and as prognostic indicators. Treatment centers around daily plasma exchange associated with immunosuppressant drug therapy, particularly steroids and more recently the monoclonal anti-CD20 antibody rituximab. Discussion: Despite improved treatment, TTP is still associated with significant mortality (10—20%, particularly when plasma exchange is initiated late. Relapse also occurs in a substantial proportion of patients (10—40% although the frequency of this outcome may be reduced by rituximab therapy.

  18. Extracorporeal Membrane Oxygenation for Adult Community-Acquired Pneumonia: Outcomes and Predictors of Mortality.

    Science.gov (United States)

    Ramanathan, Kollengode; Tan, Chuen Seng; Rycus, Peter; MacLaren, Graeme

    2017-05-01

    Extracorporeal membrane oxygenation is a rescue therapy used to support severe cardiorespiratory failure. Data on outcomes from severe community-acquired pneumonia in adults receiving rescue extracorporeal membrane oxygenation are mainly confined to single-center experiences or specific pathogens. We examined data from the Extracorporeal Life Support Organisation registry to identify risk factors for poor outcomes in adult patients with community-acquired pneumonia. Retrospective data analysis. Extracorporeal Life Support Organization Registry database. We collected deidentified data on adult patients (> 18 yr) receiving extracorporeal membrane oxygenation for community-acquired pneumonia between 2002 and 2012. Patients with incomplete data or brain death were excluded. The primary outcome measure was in-hospital mortality. Other measurements included demographic information, pre-extracorporeal membrane oxygenation mechanical ventilation and biochemical variables, inotrope requirements, extracorporeal membrane oxygenation mode, duration, and complications. Initial univariate analysis assessed potential associations between survival and various pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis to identify predictors of mortality. None. One thousand fifty-five patients, who satisfied inclusion criteria, were included in the final analysis. There was an increase in the number of patients cannulated per annum over the 10-year period studied. Univariate analysis identified pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation variables associated with high mortality. Further multiple regression analysis identified certain pre-extracorporeal membrane oxygenation factors as predictors of mortality, including duration of mechanical ventilation prior to extracorporeal membrane oxygenation, lower arterial pressure, fungal

  19. Acquired Inventors’ Productivity after Horizontal Acquisition

    DEFF Research Database (Denmark)

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    Effective integration of the R&D functions of the acquired and acquiring firms is essential for knowledge recombination after acquisition. However, prior research suggests that the post-acquisition integration process often damages the inventive labor force. We argue that an examination of the mu...

  20. [PECULIARITIES OF COMMUNITY-ACQUIRED PNEUMONIA IN CHILDREN WITH NEUROLOGICAL PATHOLOGY].

    Science.gov (United States)

    Zubarenko, O; Kopiyka, G; Kravchenko, T; Koval, L; Gurienko, K

    2017-06-01

    Neurological disorders in children highly affect the course of pneumonia, its outcome and the development of possible complications. The aim of the study was to reveal clinical and paraclinical features of community-acquired pneumonia in younger children with neurologic pathology infantile cerebral palsy. Under observation were 37 children with community-acquired pneumonia aged 1 to 3 years that suffered from spastic forms of infantile cerebral palsy. The comparison group consisted of 30 children with community-acquired pneumonia without any concomitant neurological pathology. The age of the children in the comparison and study groups was the same. The results of the study show that the presence of infantile cerebral palsy allow to relate the child to the risk group of respiratory pathology development. The course of community-acquired pneumonia in children affected by infantile cerebral palsy is characterized by rapid progression of symptoms and severity of the condition, and the clinical picture also has a number of characteristic features. Thus, cough, local physical data, classical laboratory signs of inflammation in the form of leukocytosis with neutrophil shift were noticed significantly less often in children with infantile cerebral palsy. The debut of the disease was often accompanied by bronchial obstruction, the inflammatory process was localized in the lower parts of the lungs and often matched the side of the neurologically affected part of the body. Children with cerebral palsy required a longer hospital-stay and a prolonged course of antibiotic therapy. Therefore, the risk of pneumonia in children with infantile cerebral palsy should be taken into account at the primary stage of medical care for the creation of preventive programs.

  1. 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.

  2. Gaps in patient care practices to prevent hospital-acquired delirium.

    Science.gov (United States)

    Alagiakrishnan, Kannayiram; Marrie, Thomas; Rolfson, Darryl; Coke, William; Camicioli, Richard; Duggan, D'Arcy; Launhardt, Bonnie; Fisher, Bruce; Gordon, Debbie; Hervas-Malo, Marilou; Magee, Bernice; Wiens, Cheryl

    2009-10-01

    To evaluate the current patient care practices that address the predisposing and precipitating factors contributing to the prevention of hospital-acquired delirium in the elderly. Prospective cohort (observational) study. Patients 65 years of age and older who were admitted to medical teaching units at the University of Alberta Hospital in Edmonton over a period of 7 months and who were at risk of delirium. Medical teaching units at the University of Alberta. Demographic data and information on predisposing factors for hospital-acquired delirium were obtained for all patients. Documented clinical practices that likely prevent common precipitants of delirium were also recorded. Of the 132 patients enrolled, 20 (15.2%) developed hospital-acquired delirium. At the time of admission several predisposing factors were not documented (eg, possible cognitive impairment 16 [12%], visual impairment 52 [39.4%], and functional status of activities of daily living 99 [75.0%]). Recorded precipitating factors included catheter use, screening for dehydration, and medications. Catheters were used in 35 (26.5%) patients, and fluid intake-and-output charting assessed dehydration in 57 (43.2%) patients. At the time of admission there was no documentation of hearing status in 69 (52.3%) patients and aspiration risk in 104 (78.8%) patients. After admission, reorientation measures were documented in only 16 (12.1%) patients. Although all patients had brief mental status evaluations performed once daily, this was not noted to occur twice daily (which would provide important information about fluctuation of mental status) and there was no formal attention span testing. In this study, hospital-acquired delirium was also associated with increased mortality (P < .004), increased length of stay (P < .007), and increased institutionalization (P < .027). Gaps were noted in patient care practices that might contribute to hospital-acquired delirium and also in measures to identify the development

  3. A case of an immunocompetent young man obtaining community-acquired disseminated Nocardia brasiliensis.

    Science.gov (United States)

    Li, Jinna; Cao, Jie; Wu, Yueqing; Wan, Nansheng; Pan, Li; Chen, Yuanbao

    2014-01-01

    Nocardiosis is a rare but severe pyogenic or granulomatous disease and caused by Nocardia that mainly infects immunocompromised patients. We report here a case of an immunocompetent 24-year-old male student with community-acquired pneumonia with asymptomatic disseminated cerebral abscess by Brasiliensis nocardiosis. The patient was fully recovered after receiving optimized antimicrobial therapy without relapse. This case suggests the health professionals such as the physicians of pulmonary, infection, neurology department and et al should always think about unusual cause of community acquired pneumonia, even in immunocompetent patients and when having pulmonary nocardiosis we should do a radiological neurological work up, even with the absence of neurological finding or symptom. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

    Science.gov (United States)

    Gonzaga, Vivian Fonseca; Lisboa, Gustavo Sabino; Frare, Eduardo Osório

    2017-01-01

    Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. PMID:29333168

  5. Acquired ectropion uveae and secondary glaucoma due to trauma: report of 3 cases.

    Science.gov (United States)

    Markovic, Vujica; Vukovic, Dragan; Radosavljevic, Aleksandra; Marjanovic, Ivan

    2017-01-19

    To investigate the possible association between acquired ectropion uveae and blunt trauma to the eye. We present 3 cases of acquired ectropion uveae that occurred after blunt trauma to the eye. There are no previously published data on possible association of these conditions. A retrospective review was conducted of patients with ectropion uveae and eye injury at University Eye Hospital over a 10-year period (2006-2016). We analyzed medical records and clinical findings. Three eyes of 3 male patients with ocular trauma and ectropion uveae, ages 71, 68, and 5 years, were reviewed. The period between the eye injury and the diagnosis of ectropion uveae ranged from 10 to 36 months. All 3 eyes developed clinical evidence of secondary glaucoma with moderately to severely elevated intraocular pressure (IOP) (ranging from 29 to 48 mm Hg). Surgical treatment (trabeculectomy) was needed in 2 cases in order to control secondary glaucoma and conservative treatment was sufficient in 1 case. Mean patient follow-up was 19.3 ± 4.6 months. Trauma can be considered as a cause of acquired ectropion uveae. Acquired ectropion uveae following eye trauma may be associated with significant increase in IOP. All patients in our series had secondary glaucoma and 2 of 3 required surgical treatment for IOP control.

  6. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

    Science.gov (United States)

    Zhang, Zhuo; Leong, Daniel J; Xu, Lin; He, Zhiyong; Wang, Angela; Navati, Mahantesh; Kim, Sun J; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Friedman, Joel M; Sun, Hui B

    2016-06-03

    Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan

  7. Acquired intrathoracic kidney in thoracic kyphosis

    International Nuclear Information System (INIS)

    Murayama, Sadayuki; Kawashima, Akira; Ohuchida, Toshiyuki; Russell, W.J.

    1986-12-01

    Two cases of acquired intrathoracic kidney associated with thoracic kyphosis are reported, with emphasis on the radiographic manifestations. A search of the scientific literature disclosed that the acquired type of this abnormality is rare. The importance of recognizing this entity from a differential diagnostic standpoint is underscored. (author)

  8. Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

    Science.gov (United States)

    Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

    2014-08-28

    Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

  9. And the Winner is – Acquired

    DEFF Research Database (Denmark)

    Henkel, Joachim; Rønde, Thomas; Wagner, Marcus

    value in case of success—that is, a more radical innovation. In the second stage, successful entrants bid to be acquired by the incumbent. We assume that entrants cannot survive on their own, so being acquired amounts to a ‘prize’ in a contest. We identify an equilibrium in which the incumbent chooses...

  10. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

    Science.gov (United States)

    Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

    2012-11-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units.

    Directory of Open Access Journals (Sweden)

    Vu Dinh Phu

    Full Text Available Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs. We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs across Vietnam.Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included.Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing. Pneumonia accounted for 79.4% (804/1012 of HAIs Most HAIs (84.5% [855/1012] were acquired in the survey hospital with 42.5% (363/855 acquired prior to ICU admission and 57.5% (492/855 developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76, urinary catheter (OR 2.12, no involvement of a family member in patient care (OR 1.94, and surgery after admission (OR 1.66. 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%], Pseudomonas aeruginosa (100/726 [13.8%], and Klebsiella pneumoniae (84/726 [11.6%], with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287 patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively.A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.

  12. The role of haloaerosolotherapy in immunorehabilitation of convalescents after community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Olha Lemko

    2015-02-01

    Full Text Available Aim: Investigation of the peculiarities of different haloaerosoltherapy regimes influence (treatment with different intensity of haloaerosol load upon non-specific defense and cellular immunity at convalescents after community acquired pneumonia. Objectives: patients with community acquired pneumonia in the early convalescence period (after completing antibiotic therapy, who received treatment in conditions of artificial rock salt aerosol medium (haloaerosoltherapy. Material and Methods. 42 patients with non-severe community acquired pneumonia were examined in the early convalescence period before and after the course of haloaerosoltherapy, which was prescribed after antibacterial therapy. Immunological studies included: evaluation of phagocytic activity of neutrophils (PhAN - the percentage of phagocytic neutrophils, phagocytic number (PhN - average number of latex particles absorbed by a neutrophil; metabolism of neutrophils in the test with nitroblue tetrasolium (NBT-test spontaneous and induced, which allowed to assess the functional reserve of neutrophils (FR; calculation of cytochemical coefficient (CCC for lysosomal cationic proteins (LCP and for myeloperoxidase (MPO of neutrophils; number of T- and B-lymphocytes and their subpopulations (CD3+ -, CD4+ -, CD8+ -, CD22+ - lymphocytes, calculation the number of 0- lymphocytes and the ratio of CD4+ /CD8+ lymphocytes. Laboratory examinations were also conducted in 21 practically healthy individuals (control group. Two regimes of haloaerosoltherapy were used in recovery treatment of patients with community acquired pneumonia: treating complex №1 (TC-1 with standard haloaerosol load and with increased haloaerosol load (TC-2. Results. After completion the antibiotic therapy at patients with community acquired pneumonia the moderate inhibition of phagocytic activity of neutrophils (47,6±0,58% to 55,5±1,14% in control group remained and was accompanied with a decrease in neutrophil bactericidal

  13. 7 CFR 1779.90 - Disposition of acquired property.

    Science.gov (United States)

    2010-01-01

    ... Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the final... 7 Agriculture 12 2010-01-01 2010-01-01 false Disposition of acquired property. 1779.90 Section... develop a plan to fully protect the collateral, and the lender must dispose of the collateral without...

  14. Mortality predictors in community-acquired pneumonia | Tanimowo ...

    African Journals Online (AJOL)

    acquired pneumonia to themedicalwards of Ladoke Akintola University ofTeaching Hospital between Jan. 2003 andDec. 2005. The case notes of 65 patients admitted for community-acquired pneumoniawere studiedwith respect to their admission ...

  15. Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study.

    Science.gov (United States)

    Aghaizu, Adamma; Wayal, Sonali; Nardone, Anthony; Parsons, Victoria; Copas, Andrew; Mercey, Danielle; Hart, Graham; Gilson, Richard; Johnson, Anne M

    2016-09-01

    HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV. In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression. Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0·01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; pmove towards eradication of HIV. Public Health England. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Disease burden of intensive care unit-acquired pneumonia in China: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Yaowen; Yao, Zhiyuan; Zhan, Siyan; Yang, Zhirong; Wei, Dong; Zhang, Jing; Li, Jingyi; Kyaw, Moe H

    2014-12-01

    Intensive care unit (ICU)-acquired pneumonia and ventilator-associated pneumonia (VAP) are associated with poor clinical and economic outcomes. Data regarding ICU-acquired pneumonia and VAP are not readily available from developing countries, including China. The objective of this meta-analysis was to evaluate the incidence, mortality rate, length of stay, and pathogens associated with ICU-acquired pneumonia in China. A meta-analysis and systematic review of 334 publications published between January 2007 and May 2012 and retrieved from the Chinese BioMedical database, China National Knowledge Infrastructure, VIP Chinese Science and Technique Journals database, Wanfang database, and PubMed was conducted. The incidences of ICU-acquired pneumonia and VAP were 16.2% (95% confidence interval (CI) 12.8-20.4%) and 33.7% (95% CI 31.4-36.1%), respectively; mortality rates were 37.4% (95% CI 24.6-52.2%) and 34.5% (95% CI 29.2-40.1%), respectively. The durations of stay in the ICU and hospital were 12.4 (95% CI 9.6-15.3) and 17.7 (95% CI 15.6-19.7) days and 18.0 (95% CI 16.5-19.6) and 30.5 (95% CI 26.4-34.7) days for ICU-acquired pneumonia and VAP, respectively. Pseudomonas aeruginosa (19.9%) and Acinetobacter baumannii (13.9%) were the most frequently isolated pathogens, followed by Klebsiella pneumoniae (11.9%) and Staphylococcus aureus (10.4%); 82.9% of S. aureus isolates were reported to be methicillin-resistant. ICU-acquired pneumonia/VAP remains a major cause of morbidity and mortality in patients in the ICU in China. Data on organisms causing disease in this population could help guide appropriate prevention strategies and treatment. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. CORA-13 experiment on severe fuel damage

    International Nuclear Information System (INIS)

    Firnhaber, M.; Trambauer, K.; Hagen, S.; Hofmann, P.; Schanz, G.; Sepold, L.

    1993-07-01

    The major objectives of the experiment were to investigate the behavior of PWR fuel elements during early core degradation and fast cooldown due to refill. Measured quantities are boundary conditions, bundle temperatures, hydrogen generation and the final bundle configuration. Boundary conditions which could not be measured, but which are necessary for simplified test simulation (axial power profile, shroud insulation temperature, bundle refill flow) were estimated using ATHLET-CD. The capability of the codes in calculating the main degradation phenomena has been clearly illustrated and weaknesses concerning the modelling of some degradation processes have been identified. Among the degradation phenomena involved in the test, the more severe limitations concern the UO 2 -ZrO 2 dissolution by molten Zr, the solubility limits in the resulting U-Zr-O mixture and the cladding failure by the molten mixture. There is a lack concerning the Inconel spacer-grid interactions with the rods, the material interaction between control rod material and fuel rods, and in the modelling of hydrogen generation during cooldown. (orig./DG)

  18. Thrombotic Microangiopathy in Haematopoietic Cell Transplantation: an Update

    Science.gov (United States)

    Stavrou, Evi; Lazarus, Hillard M.

    2010-01-01

    Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended. PMID:21776339

  19. THROMBOTIC MICROANGIOPATHY IN HAEMATOPOIETIC CELL TRANSPLANTATION:AN UPDATE

    Directory of Open Access Journals (Sweden)

    Evi Stavrou

    2010-10-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA. In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases, patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents.  Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

  20. Evidence for short duration of antibiotic treatment for non-severe community acquired pneumonia (CAP in children - are we there yet? A systematic review of randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Shalom Ben-Shimol

    2014-03-01

    Full Text Available Context: The ideal duration of antibiotic treatment for childhood community acquired pneumonia (CAP has not yet been established. Objective: A literature search was conducted to evaluate the efficacy of shorter than 7 days duration of oral antibiotic treatment for childhood non-severe CAP. Data sources: A systematic literature search was performed using the PubMed database. The search was limited to randomised controlled trials (RCTs conducted between January 1996 and May 2013 in children up to 18 years old. Search terms included pneumonia, treatment, duration, child, children, days, short, respiratory infection and non-severe (nonsevere. Study selection: Only RCTs of oral antibiotic treatment for non-severe CAP in children were included. Data extraction: Independent extraction of articles was done by 3 authors using a preformed questionnaire. Data synthesis: Eight articles meeting the selection criteria were identified: 7 from 2 developing countries (India and Pakistan, and 1 from a developed country (The Netherlands. Studies from developing countries used the World Health Organization clinical criteria for diagnosing CAP, which includes mainly tachypnoea. None of those studies included fever, chest radiography or any laboratory test in their case definition. The Dutch study case definition used laboratory tests and chest radiographies (x-rays in addition to clinical criteria. Five articles concluded that 3 days of treatment are sufficient for non-severe childhood CAP, 2 articles found 5 days treatment to be sufficient, and one article found no difference between 3 days of amoxicillin treatment and placebo. Conclusions: The efficacy of short duration oral antibiotic treatment for non-severe CAP in children has not been established in developed countries. Current RCTs from developing countries used clinical criteria that may have failed to appropriately identify children with true bacterial pneumonia necessitating antibiotic treatment. More RCTs

  1. Surveillance for Travel and Domestically Acquired Multidrug-Resistant Human Shigella Infections-Pennsylvania, 2006-2014.

    Science.gov (United States)

    Li, Yu Lung; Tewari, Deepanker; Yealy, Courtney C; Fardig, David; M'ikanatha, Nkuchia M

    2016-01-01

    Shigellosis is a leading cause of enteric infections in the United States. We compared antimicrobial resistance in Shigella infections related to overseas travel (travel-associated) and in those acquired domestically by analyzing antimicrobial resistance patterns, geographic distributions, and pulsed-field gel electrophoresis (PFGE) patterns. We tested samples (n = 204) from a collection of isolates recovered from patients in Pennsylvania between 2006 and 2014. Isolates were grouped into travel- and non-travel-associated categories. Eighty-one (79.4%) of the Shigella isolates acquired during international travel were resistant to multiple antibiotics compared to 53 (52.1%) of the infections transmitted in domestic settings. A majority (79.4%) of isolates associated with international travel demonstrated resistance to aminoglycosides and tetracyclines, whereas 47 (46.1%) of the infections acquired domestically were resistant to tetracycline. Almost all isolates (92.2%) transmitted in domestic settings were resistant to aminoglycosides, and 5 isolates from adult male patients were resistant to azithromycin, a drug often used for empiric treatment of severe shigellosis. Twenty (19.6%) isolates associated with illnesses acquired during overseas travel in 4 countries were resistant to quinolones. One S. sonnei PFGE pattern was traced to a multidrug-resistant isolate acquired overseas that had caused a multistate outbreak of shigellosis, suggesting global dissemination of a drug-resistant species. Resistance to certain drugs-for example, tetracycline-increased in both overseas- and domestic-acquired infections during the study period. The prevalence of resistance to macrolides (azithromycin) and third-generation cephalosporins (ceftriaxone) was less than 1%; however, efforts to better monitor changes in drug resistance over time combined with increased antimicrobial stewardship are essential at the local, national, and global levels.

  2. Preschoolers Acquire General Knowledge by Sharing in Pretense

    Science.gov (United States)

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  3. Retention of laparoscopic procedural skills acquired on a virtual-reality surgical trainer

    DEFF Research Database (Denmark)

    Nielsen, Mathilde Maagaard; Sørensen, J L; Oestergaard, Jeanett

    2011-01-01

    BACKGROUND: Virtual-reality (VR) simulator training has been shown to improve surgical performance in laparoscopic procedures in the operating room. We have, in a randomised controlled trial, demonstrated transferability to real operations. The validity of the LapSim virtual-reality simulator...... as an assessment tool has been demonstrated in several reports. However, an unanswered question regarding simulator training is the durability, or retention, of skills acquired during simulator training. The aim of the present study is to assess the retention of skills acquired using the LapSim VR simulator, 6...... and 18 months after an initial training course. METHODS AND MATERIALS: The investigation was designed as a 6- and 18-month follow-up on a cohort of participants who earlier participated in a skills training programme on the LapSim VR. The follow-up cohort consisted of trainees and senior consultants...

  4. Undiagnosed diabetes mellitus in community-acquired pneumonia

    DEFF Research Database (Denmark)

    Jensen, Andreas Vestergaard; Faurholt-Jepsen, Daniel; Egelund, Gertrud Baunbæk

    2017-01-01

    Background: Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed......-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed...... diabetes mellitus. Results: Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35-4.45]), body mass index ≥25 kg/m2 (OR, 2...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Precision grip in congenital and acquired hemiparesis: similarities in impairments and implications for neurorehabilitation - review

    Directory of Open Access Journals (Sweden)

    Yannick eBleyenheuft

    2014-06-01

    Full Text Available Background: Patients with congenital and acquired hemiparesis incur long-term functional deficits, among which the loss of prehension that may impact their functional independence. Identifying, understanding and comparing the underlying mechanisms of prehension impairments represent an opportunity to better adapt neurorehabilitationObjective: The present review aims to provide a better understanding of precision grip deficits in congenital and acquired hemiparesis and to determine whether the severity and type of fine motor control impairments depend on whether or not the lesions are congenital or acquired in adulthood. Methods: Using combinations of the following key words: fingertip force, grip force, precision grip, cerebral palsy, stroke, pubmed and Scopus databases were used to search studies from 1984 to 2013. Results: Individuals with both congenital and acquired hemiparesis were able to some extent to use anticipatory motor control in precision grip tasks, even if this control was impaired in the paretic hand. In both congenital or acquired hemiparesis, the ability to plan efficient anticipatory motor control when the less-affected hand is used provides a possibility to remediate impairments in anticipatory motor control of the paretic hand. Conclusion: Surprisingly we observed very few differences between the results of studies in children with congenital hemiplegia and stroke patients. We suggest that the underlying specific strategies of neurorehabilitation developed for each one could benefit the other.

  7. Aetiological considerations of acquired aplastic anaemia

    International Nuclear Information System (INIS)

    Malik, S.; Sarwar, I.; Mehmood, T.; Naz, F.

    2009-01-01

    Acquired aplastic anaemia is one of the important causes of pancytopenia. This study was conducted to observe the mode of presentation of acquired aplastic anaemia and to find out its possible etiological factors. Methods: It is a hospital based descriptive study of 100 patients of acquired aplastic anaemia. Results: Out of 100 patients 60 were male and 40 female. Majority (44%) of the patients were between 12 - 20 years of age. Patient presented with variable symptoms majority (40%) with fever. Most of the patients had haemoglobin levels between 4 - 6 gm/dl. (53%). Seventy percent of the cases had no obvious cause, while in 30% some known causative factors were found. Chloramphenicol was found to be the most common causative drug. Mortality was 35%. Thirty patients were partially treated and 15 were lost to follow up. Twenty patients showed improvement with treatment. Conclusions: Acquired aplastic anaemia is common among males and more prevalent in younger age group. It is idiopathic in 70% cases while 30% had some cause. It has very high mortality. Doctors need to keep in mind this fatal condition in patients presenting with anaemia and should properly investigate before prescribing antibiotics and haematinics. (author)

  8. The changing face of community-acquired methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    P Kale

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA is an important cause of infection, both in hospitalised patients with significant healthcare exposure and in patients without healthcare risk factors. Community-acquired methicillin-resistant S. aureus (CA-MRSA are known for their rapid community transmission and propensity to cause aggressive skin and soft tissue infections and community-acquired pneumonia. The distinction between the healthcare-associated (HA-MRSA and CA-MRSA is gradually fading owing to the acquisition of multiple virulence factors and genetic elements. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community or HA status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacotherapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-β-lactam antibacterial agents. This review aimed at illuminating the characteristic features of CA-MRSA, virulence factors, changing clinical settings and molecular epidemiology, insurgence into the hospital settings and therapy with drug resistance.

  9. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

    Science.gov (United States)

    Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

    2018-01-01

    Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. PMID:29642504

  10. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken.

    Science.gov (United States)

    Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

    2018-04-08

    Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism ( ACACA , FASN , SCD , ACSL5 , FADS2 , FABP1 , APOA4 and ME1 ). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

  11. Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

    Directory of Open Access Journals (Sweden)

    Yonghong Zhang

    2018-04-01

    Full Text Available Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF diet and a methionine choline-deficient (MCD diet. The results showed that the dwarf Jingxing-Huang (JXH chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL and local Beijing-You (BJY breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1. This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

  12. Phase equilibrium properties of binary aqueous solutions containing ethanediamine, 1,2-diaminopropane, 1,3-diaminopropane, or 1,4-diaminobutane at several temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Nouria Chiali-Baba [LATA2M, Laboratoire de Thermodynamique Appliquee et Modelisation Moleculaire, University AbouBekr Belkaid of Tlemcen, P.O. Box 119, Tlemcen 13000 (Algeria); Negadi, Latifa, E-mail: l_negadi@mail.univ-tlemcen.d [LATA2M, Laboratoire de Thermodynamique Appliquee et Modelisation Moleculaire, University AbouBekr Belkaid of Tlemcen, P.O. Box 119, Tlemcen 13000 (Algeria); Mokbel, Ilham; Jose, Jacques [LSA, Laboratoire des Sciences Analytiques, CNRS-UMR 5180, Universite Claude Bernard - Lyon I. 43, Bd du 11 Novembre 1918, Villeurbanne Cedex 69622 (France)

    2011-05-15

    Research highlights: Vapour pressures of ethanediamine (EDA), 1,2-diaminopropane, 1,3-diaminopropane (1,3-DAP), or 1,4-diaminobutane (1,4-DAB) aqueous solutions are reported between (293 and 363) K. The two first mixtures show negative azeotropic behaviour. The aqueous solutions of EDA, 1,2-DAP, or 1,3-DAP exhibit negative G{sup E} whereas the one containing 1,4-DAB shows either negative G{sup E} or sinusoidal shape for G{sup E}. - Abstract: The vapour pressures of {l_brace}ethanediamine (EDA) + water{r_brace}, {l_brace}1,2-diaminopropane (1,2-DAP) + water{r_brace}, {l_brace}1,3-diaminopropane (1,3-DAP) + water{r_brace} or {l_brace}1,4-diaminobutane (1,4-DAB) + water{r_brace} binary mixtures, and of pure EDA, 1,2-DAP, 1,3-DAP, 1,4-DAB, and water components were measured by means of two static devices at temperatures between (293 and 363) K. The data were correlated with the Antoine equation. From these data, the excess Gibbs function (G{sup E}) was calculated for several constant temperatures and fitted to a fourth-order Redlich-Kister equation using the Barker's method. The {l_brace}ethanediamine (EDA) + water{r_brace}, and {l_brace}1,2-diaminopropane (1,2-DAP) + water{r_brace} binary systems show negative azeotropic behaviour. The aqueous solutions of EDA, 1,2-DAP, or 1,3-DAP exhibit negative deviations in G{sup E} for all investigated temperatures over the whole composition range whereas the (1,4-DAB + water) binary mixture shows negative G{sup E} for temperatures (293.15 < T/K < 353.15) and a sinusoidal shape for G{sup E} at T = 363.15 K.

  13. Blended learning is an effective strategy for acquiring competence in public health biostatistics.

    Science.gov (United States)

    Milic, Natasa; Masic, Srdjan; Bjegovic-Mikanovic, Vesna; Trajkovic, Goran; Marinkovic, Jelena; Milin-Lazovic, Jelena; Bukumiric, Zoran; Savic, Marko; Cirkovic, Andja; Gajic, Milan; Stanisavljevic, Dejana

    2018-04-01

    We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. The trial was conducted with 69 Masters' students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p  0.8). A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students.

  14. In vivo dynamic turnover of cerebral 13C isotopomers from [U- 13C]glucose

    Science.gov (United States)

    Xu, Su; Shen, Jun

    2006-10-01

    An INEPT-based 13C MRS method and a cost-effective and widely available 11.7 Tesla 89-mm bore vertical magnet were used to detect dynamic 13C isotopomer turnover from intravenously infused [U- 13C]glucose in a 211 μL voxel located in the adult rat brain. The INEPT-based 1H → 13C polarization transfer method is mostly adiabatic and therefore minimizes signal loss due to B 1 inhomogeneity of the surface coils used. High quality and reproducible data were acquired as a result of combined use of outer volume suppression, ISIS, and the single-shot three-dimensional localization scheme built in the INEPT pulse sequence. Isotopomer patterns of both glutamate C4 at 34.00 ppm and glutamine C4 at 31.38 ppm are dominated first by a doublet originated from labeling at C4 and C5 but not at C3 (with 1JC4C5 = 51 Hz) and then by a quartet originated from labeling at C3, C4, and C5 (with 1JC3C4 = 35 Hz). A lag in the transition of glutamine C4 pattern from doublet-dominance to quartet dominance as compared to glutamate C4 was observed, which provides an independent verification of the precursor-product relationship between neuronal glutamate and glial glutamine and a significant intercompartmental cerebral glutamate-glutamine cycle between neurons and glial cells.

  15. Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis.

    Science.gov (United States)

    Arasi, Stefania; Costa, Stefano; Magazzù, Giuseppe; Ieni, Antonio; Crisafulli, Giuseppe; Caminiti, Lucia; Chiera, Fernanda; Vaccaro, Mario; Del Giudice, Michele Miraglia; Pajno, Giovanni Battista

    2016-03-22

    Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

  16. An Update on the Management Of Hospital-Acquired Pneumonia in the Elderly

    Directory of Open Access Journals (Sweden)

    Chao-Hsien Lee

    2008-12-01

    Full Text Available Pneumonia is the leading cause of infection-related death and represents the fifth cause of mortality in the elderly. There are several reported risk factors for acquiring pneumonia at an older age, such as alcoholism, lung and heart diseases, nursing home residence, and swallowing disorders. Hospital-acquired pneumonia (HAP is reviewed, with an emphasis on multidrug-resistant (MDR bacterial pathogens, such as Pseudomonas aeruginosa, Acinetobacter species, and methicillin-resistant Staphylococcus aureus. The clinical characteristics of pneumonia in the elderly differ substantially compared with younger patients, and the severity of the disease is strongly associated with increased age and age-related comorbid disorders. Streptococcus pneumoniae is the pathogen most frequently responsible for pneumonia in the elderly with early HAP without risk factors for MDR; enteric Gram-negative rods should be considered in nursing home-associated pneumonia, as well as anaerobes in patients with aspiration pneumonia. Special attention should be given to preventive measures such as vaccination, oral care, and nutrition. The management of HAP should be instituted early with: appropriate use of antibiotics in adequate doses; avoidance of excessive use of antibiotics by de-escalation of initial antibiotic therapy, based on microbiologic cultures and the clinical response of the patient; and reduction of the duration of treatment to the minimum effective period.

  17. Community acquired urinary tract infection: etiology and bacterial susceptibility

    Directory of Open Access Journals (Sweden)

    Dias Neto José Anastácio

    2003-01-01

    Full Text Available PURPOSE: Urinary tract infections (UTI are one of the most common infectious diseases diagnosed. UTI account for a large proportion of antibacterial drug consumption and have large socio-economic impacts. Since the majority of the treatments begins or is done completely empirically, the knowledge of the organisms, their epidemiological characteristics and their antibacterial susceptibility that may vary with time is mandatory. OBJECTIVE: The aim of this study was to report the prevalence of uropathogens and their antibiotic susceptibility of the community acquired UTI diagnosed in our institution and to provide a national data. METHODS: We analyzed retrospectively the results of urine cultures of 402 patients that had community acquired urinary tract infection in the year of 2003. RESULTS: The mean age of the patients in this study was 45.34 ± 23.56 (SD years. There were 242 (60.2% females and 160 (39.8% males. The most commonly isolated organism was Escherichia coli (58%. Klebsiella sp. (8.4% and Enterococcus sp.(7.9% were reported as the next most common organisms. Of all bacteria isolated from community acquired UTI, only 37% were sensitive to ampicillin, 51% to cefalothin and 52% to trimethoprim/sulfamethoxazole. The highest levels of susceptibility were to imipenem (96%, ceftriaxone (90%, amikacin (90%, gentamicin (88%, levofloxacin (86%, ciprofloxacin (73%, nitrofurantoin (77% and norfloxacin (75%. CONCLUSION: Gram-negative agents are the most common cause of UTI. Fluoroquinolones remains the choice among the orally administered antibiotics, followed by nitrofurantoin, second and third generation cephalosporins. For severe disease that require parenteral antibiotics the choice should be aminoglycosides, third generation cephalosporins, fluoroquinolones or imipenem, which were the most effective.

  18. Clinical characteristics and outcomes of acute community acquired pneumonia in children at a reference public hospital in Pernambuco State, Brazil (2010-2011

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Coelho Moraes de Brito

    Full Text Available Abstract Objectives: to describe the clinical characteristics and outcomes of acute community acquired pneumonia in children at a reference public hospital in Pernambuco State, Brazil (2010-2011 Methods: pneumonia case series of 80 children aged 28 days to 14 years old at Hospital da Restauração in Pernambuco, Brazil, from 2010 to 2011. Information was noted from medical files, and two comparison groups were created according to the severity of the disease, considering the presence of pleural effusion. Fisher or Mann-Whitney tests were used for comparative analyses. Results: severe pneumonia with pleural effusion was more frequent in children under five years of age (p=0,025, and was associated with longer period of fever (19 x 15 days and coughing (17 x 13 days, when compared to non-complicated pneumonia cases. Six children (7,5%, 6/80 died, 50% before the fourth day of hospitalization (p=0,001. All deaths were from the pleural effusion group in children from the countryside (p=0,026. Conclusions: the severity of pneumonia in children attended at this hospital is related to younger children, and those transferred from the health units in the countryside, so, early diagnosis and medical intervention are limited by infrastructure and available resources for the health.

  19. Determining the quality of life in persons with acquired brain injury

    OpenAIRE

    Balanč, Mateja

    2017-01-01

    Identifying and assessing the quality of life of persons with acquired brain injury is an important element of rehabilitation, and enables assistance and support to both the injured and their families. By identifying and assessing quality of life, we can better understand the impact of injuries on the individual and his/her life. Different levels of injuries can severely affect cognitive, physical, emotional-behavioral and social life not only of a injured person but also of members of his f...

  20. Myelofibrosis and acquired hemophilia A: a case report.

    Science.gov (United States)

    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.

  1. 14 CFR 1274.402 - Contractor acquired property.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Contractor acquired property. 1274.402 Section 1274.402 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL FIRMS Property § 1274.402 Contractor acquired property. As provided in § 1274.923...

  2. A Case of Severe Neutropenia From Short-Term Exposure to Moxifloxacin

    Directory of Open Access Journals (Sweden)

    Weihan Chen BS

    2017-03-01

    Full Text Available Moxifloxacin is commonly prescribed in the inpatient and outpatient management of community-acquired pneumonia and other common infections. We report a case of a 76-year-old man who developed severe neutropenia after several days of treatment for community-acquired pneumonia. The patient had a history of alcohol abuse; however, there were no other offending medications prescribed, and a thorough laboratory workup for other possible causes of neutropenia was negative. The patient’s neutrophils and white blood count responded quickly to cessation of fluoroquinolones. This case highlights the importance of identifying patients that might be at high risk for neutropenia that may need closer monitoring on this commonly prescribed medication.

  3. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

    Science.gov (United States)

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-01-01

    Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  4. Launch of the I13-2 data beamline at the Diamond Light Source synchrotron

    International Nuclear Information System (INIS)

    Bodey, A J; Rau, C

    2017-01-01

    Users of the Diamond-Manchester Imaging Branchline I13-2 commonly spend many months analysing the large volumes of tomographic data generated in a single beamtime. This is due to the difficulties inherent in performing complicated, computationally-expensive analyses on large datasets with workstations of limited computing power. To improve productivity, a ‘data beamline’ was launched in January 2016. Users are scheduled for visits to the data beamline in the same way as for regular beamlines, with bookings made via the User Administration System and provision of financial support for travel and subsistence. Two high-performance graphics workstations were acquired, with sufficient RAM to enable simultaneous analysis of several tomographic volumes. Users are given high priority on Diamond’s central computing cluster for the duration of their visit, and if necessary, archived data are restored to a high-performance disk array. Within the first six months of operation, thirteen user visits were made, lasting an average of 4.5 days each. The I13-2 data beamline was the first to be launched at Diamond Light Source and, to the authors’ knowledge, the first to be formalised in this way at any synchrotron. (paper)

  5. Launch of the I13-2 data beamline at the Diamond Light Source synchrotron

    Science.gov (United States)

    Bodey, A. J.; Rau, C.

    2017-06-01

    Users of the Diamond-Manchester Imaging Branchline I13-2 commonly spend many months analysing the large volumes of tomographic data generated in a single beamtime. This is due to the difficulties inherent in performing complicated, computationally-expensive analyses on large datasets with workstations of limited computing power. To improve productivity, a ‘data beamline’ was launched in January 2016. Users are scheduled for visits to the data beamline in the same way as for regular beamlines, with bookings made via the User Administration System and provision of financial support for travel and subsistence. Two high-performance graphics workstations were acquired, with sufficient RAM to enable simultaneous analysis of several tomographic volumes. Users are given high priority on Diamond’s central computing cluster for the duration of their visit, and if necessary, archived data are restored to a high-performance disk array. Within the first six months of operation, thirteen user visits were made, lasting an average of 4.5 days each. The I13-2 data beamline was the first to be launched at Diamond Light Source and, to the authors’ knowledge, the first to be formalised in this way at any synchrotron.

  6. How are Concepts of Infinity Acquired?

    Directory of Open Access Journals (Sweden)

    Trzęsicki Kazimierz

    2015-03-01

    Full Text Available Concepts of infinity have been subjects of dispute since antiquity. The main problems of this paper are: is the mind able to acquire a concept of infinity? and: how are concepts of infinity acquired? The aim of this paper is neither to say what the meanings of the word “infinity” are nor what infinity is and whether it exists. However, those questions will be mentioned, but only in necessary extent.

  7. Acquired hypofibrinogenemia: current perspectives

    Directory of Open Access Journals (Sweden)

    Besser MW

    2016-09-01

    Full Text Available Martin W Besser,1 Stephen G MacDonald2 1Department of Haematology, 2Department of Specialist Haemostasis, The Pathology Partnership, Addenbrooke’s Hospital, Cambridge, UK Abstract: Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. Keywords: Clauss fibrinogen assay, fibrinogen antigen, viscoelastic testing, ­gravimetric fibrinogen assay, PT-derived fibrinogen, functional fibrinogen, direct oral anticoagulant, dysfibrinogenemia, afibrinogenemia

  8. Pneumonia - children - community acquired

    Science.gov (United States)

    Bronchopneumonia - children; Community-acquired pneumonia - children; CAP - children ... Viruses are the most common cause of pneumonia in infants and children. Ways your child can get CAP include: Bacteria and viruses living in the nose, sinuses, or mouth may spread ...

  9. Monitoring Agitated Behavior After acquired Brain Injury

    DEFF Research Database (Denmark)

    Aadal, Lena; Mortensen, Jesper; Nielsen, Jørgen Feldbaek

    2016-01-01

    Purpose: To describe the onset, duration, intensity, and nursing shift variation of agitated behavior in patients with acquired brain injury (ABI) at a rehabilitation hospital. Design: Prospective descriptive study. Methods: A total of 11 patients with agitated behavior were included. Agitated...... behavior was registered with the Agitated Behavior Scale (ABS). The nurse or therapist allocated the individual patient assessed ABS during each shift. Intensity of agitated behavior was tested using exact test. A within-subject shift effect was analyzed with repeated-measure ANOVA. Findings: The onset...... of agitated behavior was at a median of 14 (1–28) days from admission. Seven patients remained agitated beyond 3 weeks from onset. Severe intensity of agitation was observed in 86 of 453 nursing shifts. Differences in agitated behavior between day, evening, and night shifts were found, F(2.20) = 7.90, p...

  10. Antibiotic resistance patterns of pediatric community-acquired urinary infections

    Directory of Open Access Journals (Sweden)

    Eliana Biondi Medeiros Guidoni

    Full Text Available Knowledge about antimicrobial resistance patterns of the etiological agents of urinary tract infections (UTIs is essential for appropriate therapy. Urinary isolates from symptomatic UTI cases attended at Santa Casa University Hospital of São Paulo from August 1986 to December 1989 and August 2004 to December 2005 were identified by conventional methods. Antimicrobial resistance testing was performed by Kirby Bauer's disc diffusion method. Among the 257 children, E. coli was found in 77%. A high prevalence of resistance was observed against ampicillin and TMP/SMX (55% and 51%. The antibiotic resistance rates for E. coli were: nitrofurantoin (6%, nalidixic acid (14%, 1st generation cephalosporin (13%, 3rd generation cephalosporins (5%, aminoglycosides (2%, norfloxacin (9% and ciprofloxacin (4%. We found that E. coli was the predominant bacterial pathogen of community-acquired UTIs. We also detected increasing resistance to TMP/SMX among UTI pathogens in this population.

  11. Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia.

    Science.gov (United States)

    Woollams, Anna M

    2014-01-01

    Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders.

  12. Severe storm in Bavaria, the Czech Republic and Poland on 12–13 July 1984: A statistic- and model-based analysis

    Czech Academy of Sciences Publication Activity Database

    Kašpar, Marek; Müller, Miloslav; Kakos, Vilibald; Řezáčová, Daniela; Sokol, Zbyněk

    2009-01-01

    Roč. 93, 1-3 (2009), s. 99-110 ISSN 0169-8095. [European Conference on Severe Storms /4./. Miramare -Trieste, 10.09.2007-14.09.2007] R&D Projects: GA ČR GA205/07/0905; GA AV ČR KJB300420701; GA AV ČR KJB300420802 Institutional research plan: CEZ:AV0Z30420517 Keywords : convective storm * synoptic anomaly * mesoscale condition * forecast verification * gust front Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.811, year: 2009 http://www. elsevier.com/locate/atmos

  13. Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature

    Directory of Open Access Journals (Sweden)

    Maja Ogielska

    2015-08-01

    Conclusions: CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation.

  14. Ultrasound Imaging. Chapter 13

    Energy Technology Data Exchange (ETDEWEB)

    Lacefield, J. C. [University of Western Ontario, London (Canada)

    2014-09-15

    In the conventional method of ultrasonography, images are acquired in reflection, or pulse echo, mode. An array of small piezoelectric elements transmits a focused pulse along a specified line of sight known as a scan line. Echoes returning from the tissue are received by the same array, focused via the delay-and-sum beam forming process reviewed in Section 13.2, and demodulated to obtain the magnitude, or envelope, of the echo signal. The scanner measures the arrival time of the echoes relative to the time the pulse was transmitted and maps the arrival time to the distance from the array, using an assumed speed of sound. The earliest ultrasound systems would display the result of a single pulse acquisition in 1-D A-mode (amplitude mode) format by plotting echo magnitude as a function of distance. A 2-D or 3-D B-mode (brightness mode) image is acquired by performing a large number of pulse echo acquisitions, incrementally increasing the scan line direction between each pulse echo operation, to sweep out a 2-D or 3-D field of view (FOV). The term B-mode imaging reflects the fact that the echo magnitude from each point in the FOV is mapped to the grey level, or brightness, of the corresponding pixel in the image.

  15. Do alterations in follicular fluid proteases contribute to human infertility?

    Science.gov (United States)

    Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

    2015-05-01

    Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

  16. 19 CFR 148.33 - Articles acquired abroad.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

  17. Acquired hypertrichosis lanuginosa

    Directory of Open Access Journals (Sweden)

    Kumar Pramod

    1993-01-01

    Full Text Available Acquired hypertirichosis lanuginose developed rapidly in a patient with no detectable malignancy. Soft, fine, downy hair growth was noticed on the face, ears, limbs and trunk. Bilaterally symmetrical vitiliginous macules were present on the ear and preauricular region. This case is reported because of its rarity, absence of any detectable malignancy and development of vitiligo, which to our knowledge has not been reported earlier.

  18. Effectiveness of a Very Early Stepping Verticalization Protocol in Severe Acquired Brain Injured Patients: A Randomized Pilot Study in ICU.

    Science.gov (United States)

    Frazzitta, Giuseppe; Zivi, Ilaria; Valsecchi, Roberto; Bonini, Sara; Maffia, Sara; Molatore, Katia; Sebastianelli, Luca; Zarucchi, Alessio; Matteri, Diana; Ercoli, Giuseppe; Maestri, Roberto; Saltuari, Leopold

    2016-01-01

    Verticalization was reported to improve the level of arousal and awareness in patients with severe acquired brain injury (ABI) and to be safe in ICU. We evaluated the effectiveness of a very early stepping verticalization protocol on their functional and neurological outcome. Consecutive patients with Vegetative State or Minimally Conscious State were enrolled in ICU on the third day after an ABI. They were randomized to undergo conventional physiotherapy alone or associated to fifteen 30-minute sessions of verticalization, using a tilt table with robotic stepping device. Once stabilized, patients were transferred to our Neurorehabilitation unit for an individualized treatment. Outcome measures (Glasgow Coma Scale, Coma Recovery Scale revised -CRSr-, Disability Rating Scale-DRS- and Levels of Cognitive Functioning) were assessed on the third day from the injury (T0), at ICU discharge (T1) and at Rehab discharge (T2). Between- and within-group comparisons were performed by the Mann-Whitney U test and Wilcoxon signed-rank test, respectively. Of the 40 patients enrolled, 31 completed the study without adverse events (15 in the verticalization group and 16 in the conventional physiotherapy). Early verticalization started 12.4±7.3 (mean±SD) days after ABI. The length of stay in ICU was longer for the verticalization group (38.8 ± 15.7 vs 25.1 ± 11.2 days, p = 0.01), while the total length of stay (ICU+Neurorehabilitation) was not significantly different (153.2 ± 59.6 vs 134.0 ± 61.0 days, p = 0.41). All outcome measures significantly improved in both groups after the overall period (T2 vs T0, pverticalization protocol, started since the acute stages, improves the short-term and long-term functional and neurological outcome of ABI patients. clinicaltrials.gov NCT02828371.

  19. Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection.

    Science.gov (United States)

    Henriquez, Kelsey M; Hayney, Mary S; Xie, Yaoguo; Zhang, Zhengjun; Barrett, Bruce

    2015-02-01

    Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s)  = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. © 2014 Wiley Periodicals, Inc.

  20. Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan.

    Science.gov (United States)

    Sada, Ryuichi; Fukuda, Saori; Ishimaru, Hiroyasu

    2017-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus has been spreading worldwide, including in Japan. However, few cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus have been reported in Japan. We report 2 cases, in middle-aged women, of toxic shock syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus via a vaginal portal of entry. The first patient had used a tampon and the second patient had vaginitis due to a cleft narrowing associated with vulvar lichen sclerosus. Both patients were admitted to our hospital with septic shock and severe acute kidney injury and subsequently recovered with appropriate antibiotic treatment. In our review of the literature, 8 cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus were reported in Japan. In these 8 cases, the main portals of entry were the skin and respiratory tract; however, the portal of entry of Community-acquired methicillin-resistant Staphylococcus aureus from a vaginal lesion has not been reported in Japan previously.

  1. Molecular Characterization of Streptococcus agalactiae Causing Community- and Hospital-acquired Infections in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Haoqin Jiang

    2016-08-01

    Full Text Available Streptococcus agalactiae, a colonizing agent in pregnant women and the main cause of neonatal sepsis and meningitis, has been increasingly associated with invasive disease in nonpregnant adults. We collected a total of 87 non-repetitive S. agalactiae isolates causing community-acquired (CA and hospital-acquired (HA infections in nonpregnant adults from a teaching hospital in Shanghai between 2009 and 2013. We identified and characterized their antibiotic resistance, sequence type (ST, serotype, virulence, and biofilm formation. The most frequent STs were ST19 (29.9%, ST23 (16.1%, ST12 (13.8%, and ST1 (12.6%. ST19 had significantly different distributions between CA- and HA-group B Streptococci (GBS isolates. The most frequent serotypes were III (32.2%, Ia (26.4%, V (14.9%, Ib (13.8%, and II (5.7%. Serotype III/ST19 was significantly associated with levofloxacin resistance in all isoates. The HA-GBS multidrug resistant rate was much higher than that of CA-GBS. Virulence genes pavA, cfb were found in all isolates. Strong correlations exist between serotype Ib (CA and HA and surface protein genes spb1 and bac, serotype III (HA and surface protein gene cps and GBS pilus cluster. The serotype, epidemic clone, PFGE-based genotype, and virulence gene are closely related between CA-GBS and HA-GBS, and certain serotypes and clone types were significantly associated with antibiotic resistance. However, CA-GBS and HA-GBS still had significant differences in their distribution of clone types, antibiotic resistance, and specific virulence genes, which may provide a basis for infection control.

  2. Prevalence and resistance pattern of Moraxella catarrhalis in community-acquired lower respiratory tract infections

    Directory of Open Access Journals (Sweden)

    Shaikh SBU

    2015-07-01

    Full Text Available Safia Bader Uddin Shaikh, Zafar Ahmed, Syed Ali Arsalan, Sana Shafiq Department of Pulmonology, Liaquat National Hospital, Karachi, Pakistan Introduction: Moraxella catarrhalis previously considered as commensal of upper respiratory tract has gained importance as a pathogen responsible for respiratory tract infections. Its beta-lactamase-producing ability draws even more attention toward its varying patterns of resistance. Methods: This was an observational study conducted to evaluate the prevalence and resistance pattern of M. catarrhalis. Patients aged 20–80 years admitted in the Department of Chest Medicine of Liaquat National Hospital from March 2012 to December 2012 were included in the study. Respiratory samples of sputum, tracheal secretions, and bronchoalveolar lavage were included, and their cultures were followed. Results: Out of 110 respiratory samples, 22 showed positive cultures for M. catarrhalis in which 14 were males and eight were females. Ten samples out of 22 showed resistance to clarithromycin, and 13 samples out of 22 displayed resistance to erythromycin, whereas 13 showed resistance to levofloxacin. Hence, 45% of the cultures showed resistance to macrolides so far and 59% showed resistance to quinolones. Conclusion: Our study shows that in our environment, M. catarrhalis may be resistant to macrolides and quinolones; hence, these should not be recommended as an alternative treatment in community-acquired lower respiratory tract infections caused by M. catarrhalis. However, a study of larger sample size should be conducted to determine if the recommendations are required to be changed. Keywords: community-acquired lower respiratory tract infections or pneumonia, M. catarrhalis, antibiotic resistance, gram-negative diplococcic, Pakistan

  3. From Bad to Worse: Anemia on Admission and Hospital-Acquired Anemia.

    Science.gov (United States)

    Koch, Colleen G; Li, Liang; Sun, Zhiyuan; Hixson, Eric D; Tang, Anne S; Phillips, Shannon C; Blackstone, Eugene H; Henderson, J Michael

    2017-12-01

    Anemia at hospitalization is often treated as an accompaniment to an underlying illness, without active investigation, despite its association with morbidity. Development of hospital-acquired anemia (HAA) has also been associated with increased risk for poor outcomes. Together, they may further heighten morbidity risk from bad to worse. The aims of this study were to (1) examine mortality, length of stay, and total charges in patients with present-on-admission (POA) anemia and (2) determine whether these are exacerbated by development of HAA. In this cohort investigation, from January 1, 2009, to August 31, 2011, a total of 44,483 patients with POA anemia were admitted to a single health system compared with a reference group of 48,640 without POA anemia or HAA. Data sources included the University HealthSystem Consortium database and electronic medical records. Risk-adjustment methods included logistic and linear regression models for mortality, length of stay, and total charges. Present-on-admission anemia was defined by administrative coding. Hospital-acquired anemia was determined by changes in hemoglobin values from the electronic medical record. Approximately one-half of the patients experienced worsening of anemia with development of HAA. Risk for death and resource use increased with increasing severity of HAA. Those who developed severe HAA had 2-fold greater odds for death; that is, mild POA anemia with development of severe HAA resulted in greater mortality (odds ratio, 2.57; 95% confidence interval, 2.08-3.18; P < 0.001), increased length of stay (2.23; 2.16-2.31; P < 0.001), and higher charges (2.09; 2.03-2.15; P < 0.001). Present-on-admission anemia is associated with increased mortality and resource use. This risk is further increased from bad to worse when patients develop HAA. Efforts to address POA anemia and HAA deserve attention.

  4. Predictability of depression severity based on posterior alpha oscillations

    NARCIS (Netherlands)

    Jiang, H.; Popov, T.; Jylänki, P.P.; Bi, K.; Yao, Z.; Lu, Q.; Jensen, O.; Gerven, M.A.J. van

    2016-01-01

    Objective: We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity. Methods: MEG data was acquired from 22 MDD patients and 22 healthy controls (HC) resting awake with eyes closed. Individual power spectra

  5. IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

    Science.gov (United States)

    Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

    2017-10-01

    IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Refractor y thrombotic thrombocytopenic pur pura following acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Ebisa Bekele

    2016-09-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a rare blood disorder with an estimated incidence of 4–5 cases per million people per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia and organ damage. There are reports in literature that TTP and acute pancreatitis are associated, indicating each can be the cause of the other. However, acute pancreatitis triggering TTP is very rare. A 71 years old female presented with abdominal pain of 3 days, followed by dark urine. She had icteric sclera, petechial rash and mild epigastric tenderness. Lab findings were significant for hemolytic anemia, thrombocytopenia and elevated lipase. CT of abdomen showed evidence of pancreatitis and cholelithiasis. After admission, patient developed symptoms of stroke. Further investigation showed elevated lactate dehydrogenase and normal coagulation studied with peripheral blood smear showed 5–6 schistocytes/high power field. Disintegrin and metalloproteinase with thrombospondin motifs-13 (ADAMTS13 activity showed less than 3% with high ADAMTS13 inhibitor 2.2. Patient required 6–7 weeks of daily plasmapheresis until she showed complete response. Our patient presented with clinical features of pancreatitis prior to having dark urine and petechial rash. Therefore, we strongly believe that our patient had pancreatitis which was followed by TTP. Patient's ADMTS13 activity was 6% after 10 plasma exchanges, signifying refractory TTP and higher risk for morbidity and mortality. There are limited data and consensus on the management of refractory TTP. TTP and acute pancreatitis are associated. However, refractory TTP following acute pancreatitis is rarely mentioned in the literature. We would like to emphasize the importance of having higher clinical suspicion of the association of both disease entities.

  7. Etiology and outcome of community-acquired lung abscess.

    Science.gov (United States)

    Takayanagi, Noboru; Kagiyama, Naho; Ishiguro, Takashi; Tokunaga, Daidou; Sugita, Yutaka

    2010-01-01

    Anaerobes are the first and Streptococcus species the second most common cause of community-acquired lung abscess (CALA) in the West. The etiologic pathogens of this disease have changed in Taiwan, with Klebsiella pneumoniae being reported as the most common cause of CALA. To determine the etiologies of community-acquired lung abscess. We retrospectively reviewed the records of 205 Japanese adult patients with CALA to evaluate etiologies and outcomes. We used not only traditional microbiological investigations but also percutaneous ultrasonography-guided transthoracic needle aspiration and protected specimen brushes. Of these 205 patients, 122 had documented bacteriological results, with 189 bacterial species isolated. Pure aerobic, mixed aerobic and anaerobic, and pure anaerobic bacteria were isolated in 90 (73.8%), 17 (13.9%), and 15 (12.3%) patients, respectively. The four most common etiologic pathogens were Streptococcus species (59.8%), anaerobes (26.2%), Gemella species (9.8%), and K. pneumoniae (8.2%). Streptococcus mitis was the most common among the Streptococcus species. Mean duration of antibiotic administration was 26 days. Six patients (2.9%, 3 with actinomycosis and 3 with nocardiosis) were treated with antibiotics for 76-189 days. Two patients with anaerobic lung abscess died. The first and second most common etiologic pathogens of CALA in our hospital were Streptococcus species and anaerobes, respectively. The etiologies in our study differ from those in Taiwan and are similar to those in the West with the exception that Streptococcus species were the most common etiologic pathogens in our study whereas anaerobes are the most frequent etiologic pathogens in Western countries. S. mitis and Gemella species are important etiologic pathogens as well. The identification of Actinomyces and Nocardia is important in order to define the adequate duration of antibiotic administration. Copyright 2010 S. Karger AG, Basel.

  8. Langerhans cell precursors acquire RANK/CD265 in prenatal human skin.

    Science.gov (United States)

    Schöppl, Alice; Botta, Albert; Prior, Marion; Akgün, Johnnie; Schuster, Christopher; Elbe-Bürger, Adelheid

    2015-01-01

    The skin is the first barrier against foreign pathogens and the prenatal formation of a strong network of various innate and adaptive cells is required to protect the newborn from perinatal infections. While many studies about the immune system in healthy and diseased adult human skin exist, our knowledge about the cutaneous prenatal/developing immune system and especially about the phenotype and function of antigen-presenting cells such as epidermal Langerhans cells (LCs) in human skin is still scarce. It has been shown previously that LCs in healthy adult human skin express receptor activator of NF-κB (RANK), an important molecule prolonging their survival. In this study, we investigated at which developmental stage LCs acquire this important molecule. Immunofluorescence double-labeling of cryostat sections revealed that LC precursors in prenatal human skin either do not yet [10-11 weeks of estimated gestational age (EGA)] or only faintly (13-15 weeks EGA) express RANK. LCs express RANK at levels comparable to adult LCs by the end of the second trimester. Comparable with adult skin, dermal antigen-presenting cells at no gestational age express this marker. These findings indicate that epidermal leukocytes gradually acquire RANK during gestation - a phenomenon previously observed also for other markers on LCs in prenatal human skin. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  9. Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

    DEFF Research Database (Denmark)

    Villiers, Carin P.De; Hedley, Paula L.; Placing, Sophie

    2017-01-01

    Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. PP13 was measured in first trimester (week 10...

  10. [Increasing incidence of community-acquired pneumonia caused by atypical microorganisms].

    Science.gov (United States)

    Tazón-Varela, M A; Alonso-Valle, H; Muñoz-Cacho, P; Gallo-Terán, J; Piris-García, X; Pérez-Mier, L A

    2017-09-01

    Knowing the most common microorganisms in our environment can help us to make proper empirical treatment decisions. The aim is to identify those microorganisms causing community-acquired pneumonia. An observational, descriptive and prospective study was conducted, including patients over 14 years with a clinical and radiographic diagnosis of community-acquired pneumonia during a 383 consecutive day period. A record was made of sociodemographic variables, personal history, prognostic severity scales, progress, and pathogenic agents. The aetiological diagnosis was made using blood cultures, detection of Streptococcus pneumoniae and Legionella pneumophila urinary antigens, sputum culture, influenza virus and Streptococcus pyogenes detection. Categorical variables are presented as absolute values and percentages, and continuous variables as their means and standard deviations. Of the 287 patients included in the study (42% women, mean age 66±22 years), 10.45% died and 70% required hospital admission. An aetiological diagnosis was achieved in 43 patients (14.98%), with 16 microorganisms found in 59 positive samples. The most frequently isolated pathogen was Streptococcus pneumonia (24/59, 41%), followed by gram-negative enteric bacilli, Klebsiella pneumonia, Escherichia coli, Serratia marcescens and Enterobacter cloacae isolated in 20% of the samples (12/59), influenza virus (5/59, 9%), methicillin-resistant Staphylococcus aureus (3/59, 5%), Pseudomonas aeruginosa (2/59, 3%), Moraxella catarrhalis (2/59, 3%), Legionella pneumophila (2/59, 3%), and Haemophilus influenza (2/59, 3%). Polymicrobial infections accounted for 14% (8/59). A high percentage of atypical microorganisms causing community-acquired pneumonia were found. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Clinical significance of acquired somatic mutations in aplastic anaemia.

    Science.gov (United States)

    Marsh, J C W; Mufti, G J

    2016-08-01

    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.

  12. Quick look report, entry 4: Three Mile Island Unit 2, November 13, 1980

    International Nuclear Information System (INIS)

    Eidam, G.E.

    1981-06-01

    This report summarizes tasks performed during entry 4 at Three Mile Island Unit 2. During the entry into containment, which was made on November 13, 1980, additional beta and gamma surveys were conducted to supplement data acquired on previous entries. A decontamination test was completed on Elevation 305. Power receptables tested on Elevation 305 were deenergized, but receptacles on Elevation 347 were energized. Still photography was acquired of Elevations 305 and 347. During the entry, 86 still photographs were taken. Videotaping (color and black and white) was done on Elevations 305 and 347, but lighting on both elevations was insufficient for high-quality video

  13. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

    NARCIS (Netherlands)

    Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

    2015-01-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 +/- A 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups

  14. Community acquired Pseudomonas aeruginosa pneumonia in a young athlete man: a case report and literature review.

    Science.gov (United States)

    Rahdar, Hossein Ali; Kazemian, Hossein; Bimanand, Lida; Zahedani, Shahram Shahraki; Feyisa, Seifu Gizaw; Taki, Elahe; Havaei, Seyed Asghar; Karami-Zarandi, Morteza

    2018-04-10

    Pseudomonas aeruginosa is commonly known as nosocomial infection agent but rarely previously healthy peoples infected by P. aeruginosa. Here we report community acquired pneumonia in a 27 years old athleteman. 15 published P. aeruginosa CAP case reports are reviewed.1 53.3% of patients was female and 46.67% was male. The mean age was 44 years old (SD: ±13.54). In 8 report it is mentioned that the patient was smoker. Fatality rate was 46.6% and death rate was not significantly different between selected antibiotic regimen, sex and smoking in patient's outcome. Chest strike can be a risk factor for P. aeruginosa CAP in athlete people. Our reported patient treated by ciprofloxacin 400 mg per day and healed without any Secondary complication. Fast and timelymanner diagnosis and treatment is critical in Community acquired P. aeruginosapneumonia outcome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. 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.

  16. Hospital-Acquired Condition Reduction Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — In October 2014, CMS began reducing Medicare payments for subsection (d) hospitals that rank in the worst performing quartile with respect to hospital-acquired...

  17. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma

    NARCIS (Netherlands)

    Verkleij, Marieke; van de Griendt, E-J.; Colland, V.; Van Loey, N.E.E.; Beelen, A.; Geenen, R.

    2015-01-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in

  18. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test

    NARCIS (Netherlands)

    Curvers, J; Thomassen, MCLGD; Rimmer, J; Hamulyak, K; van der Meer, J; Tans, G; Preston, FE; Rosing, J

    Background. Several hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.

  19. Clinicians' ability, motivation, and opportunity to acquire and transfer knowledge: An age-driven perspective.

    Science.gov (United States)

    Profili, Silvia; Sammarra, Alessia; Dandi, Roberto; Mascia, Daniele

    2017-11-08

    Many countries are seeing a dramatic increase in the average age of their clinicians. The literature often highlights the challenges of high replacement costs and the need for strategies to retain older personnel. Less discussed are the potential pitfalls of knowledge acquisition and transfer that accompany this aging issue. We propose a conceptual framework for understanding how clinicians' age interact with ability, motivation, and opportunity to predict clinical knowledge transfer and acquisition in health care organizations. This study integrates life-span development perspectives with the ability-motivation-opportunity framework to develop a number of testable propositions on the interaction between age and clinicians' ability, motivation, and opportunity to acquire and transfer clinical knowledge. We posit that the interaction between ability (the knowledge and skills to acquire knowledge), motivation (the willingness to acquire and transfer knowledge), and opportunity (resources required for acquiring and transferring knowledge) is a determinant of successful knowledge management. We also suggest that clinicians' age-and more specifically, the cognitive and motivational changes that accompany aging-moderates these relationships. This study contributes to existing research by offering a set of testable propositions for future research. These propositions will hopefully encourage empirical research into this important topic and lead to guidelines for reducing the risks of organizational knowledge loss due to aging. We suggest several ways that health care organizations can tailor managerial practices in order to help capitalize on the knowledge-based resources held by their younger and older clinicians. Such initiatives may affect employees' ability (e.g., by providing specific training programs), motivation (e.g., by expanding subjective perceptions of future time at work), and opportunities (e.g., by providing mentoring, reverse mentoring, and coaching

  20. AETIOLOGY OF ACQUIRED LOWER MOTOR NEURON TYPE OF FACIAL NERVE PARALYSIS– A DESCRIPTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Arya Devi Karangat

    2018-02-01

    Full Text Available BACKGROUND This study was conducted to evaluate the various aetiologies of acquired lower motor neuron type of facial nerve paralysis, assessment of severity of lesion and outcome through follow up. 47 patients between 15-75 years were studied. MATERIALS AND METHODS All patients with acquired LMN facial paralysis who presented to our department were included in the study. They were evaluated with history, clinical examination and investigations. They were treated and followed up for a period of 6 months. RESULTS The most common aetiology identified for facial palsy was trauma which was non-iatrogenic. The anatomic level which predominated in our patients was infrastapedial. Maximum number of patients presented with grade 4 facial palsy. CONCLUSION Non- iatrogenic trauma was the most common cause among the patients studied and follow up of these patients had a good recovery of 60%.

  1. Acquired ichthyosis with hoffman's syndrome

    Directory of Open Access Journals (Sweden)

    Sathyanarayana B

    2003-01-01

    Full Text Available A middle aged man presented with features of acquired ichthyosis with Hoffman's syndrome. Laboratory tests support hypothyodism. Myoedema and hypertrophy of muscles were present. Patient was previously treated for Pellagra.

  2. [Community-acquired bacteremia in adult patients attending the emergency service of a teaching hospital].

    Science.gov (United States)

    Artico, Muriel J; Rocchi, Marta; Gasparotto, Ana; Ocaña Carrizo, Valeria; Navarro, Mercedes; Mollo, Valeria; Avilés, Natalia; Romero, Vanessa; Carrillo, Sonia; Monterisi, Aída

    2012-01-01

    Bacteremia is an important cause of morbimortality. This study describes the episodes of community-acquired bacteremia in adult patients registered at our hospital. Between January 2005, and December 2009, 271 episodes were studied. The diagnostic yield of blood cultures was 13.5 %. A total of 52 % of patients were male and 48 % female. The mean age was 60. The most frequent comorbidities were: diabetes (21 %), neoplasia (18 %), cardiopathy (11 %), and HIV infection (8 %). The focus was- respiratory (21 %), urinary (15 %), cutaneous (9 %), and others (13 %). Gram-positive bacteria prevailed (51.4%). The most frequent microorganisms were Escherichia coli (25 %), Streptococcus pneumoniae (22.9 %), and Staphylococcus aureus (12.3 %). Bacteremia was polymicrobial in 7 % of the cases. Thirty three percent of E. coli isolates were resistant to ciprofloxacin and 6 % to ceftazidime. Fourteen percent of S. aureus strains were resistant to oxacillin whereas only 7 % of S. pneumoniae expressed high resistance to penicillin with MICs = 2 ug/ml, according to meningitis breakpoints.

  3. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    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.

  4. The Short Wave Aerostat-Mounted Imager (SWAMI): A novel platform for acquiring remotely sensed data from a tethered balloon

    Science.gov (United States)

    Vierling, L.A.; Fersdahl, M.; Chen, X.; Li, Z.; Zimmerman, P.

    2006-01-01

    We describe a new remote sensing system called the Short Wave Aerostat-Mounted Imager (SWAMI). The SWAMI is designed to acquire co-located video imagery and hyperspectral data to study basic remote sensing questions and to link landscape level trace gas fluxes with spatially and temporally appropriate spectral observations. The SWAMI can fly at altitudes up to 2 km above ground level to bridge the spatial gap between radiometric measurements collected near the surface and those acquired by other aircraft or satellites. The SWAMI platform consists of a dual channel hyperspectral spectroradiometer, video camera, GPS, thermal infrared sensor, and several meteorological and control sensors. All SWAMI functions (e.g. data acquisition and sensor pointing) can be controlled from the ground via wireless transmission. Sample data from the sampling platform are presented, along with several potential scientific applications of SWAMI data.

  5. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery.

    Science.gov (United States)

    Sihvonen, Aleksi J; Ripollés, Pablo; Rodríguez-Fornells, Antoni; Soinila, Seppo; Särkämö, Teppo

    2017-01-01

    Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV) and white matter volume (WMV) changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients ( N = 90), we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered) amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered) amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of the lesions

  6. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery

    Science.gov (United States)

    Sihvonen, Aleksi J.; Ripollés, Pablo; Rodríguez-Fornells, Antoni; Soinila, Seppo; Särkämö, Teppo

    2017-01-01

    Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV) and white matter volume (WMV) changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients (N = 90), we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered) amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered) amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of the lesions

  7. Revisiting the Neural Basis of Acquired Amusia: Lesion Patterns and Structural Changes Underlying Amusia Recovery

    Directory of Open Access Journals (Sweden)

    Aleksi J. Sihvonen

    2017-07-01

    Full Text Available Although, acquired amusia is a common deficit following stroke, relatively little is still known about its precise neural basis, let alone to its recovery. Recently, we performed a voxel-based lesion-symptom mapping (VLSM and morphometry (VBM study which revealed a right lateralized lesion pattern, and longitudinal gray matter volume (GMV and white matter volume (WMV changes that were specifically associated with acquired amusia after stroke. In the present study, using a larger sample of stroke patients (N = 90, we aimed to replicate and extend the previous structural findings as well as to determine the lesion patterns and volumetric changes associated with amusia recovery. Structural MRIs were acquired at acute and 6-month post-stroke stages. Music perception was behaviorally assessed at acute and 3-month post-stroke stages using the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA. Using these scores, the patients were classified as non-amusic, recovered amusic, and non-recovered amusic. The results of the acute stage VLSM analyses and the longitudinal VBM analyses converged to show that more severe and persistent (non-recovered amusia was associated with an extensive pattern of lesions and GMV/WMV decrease in right temporal, frontal, parietal, striatal, and limbic areas. In contrast, less severe and transient (recovered amusia was linked to lesions specifically in left inferior frontal gyrus as well as to a GMV decrease in right parietal areas. Separate continuous analyses of MBEA Scale and Rhythm scores showed extensively overlapping lesion pattern in right temporal, frontal, and subcortical structures as well as in the right insula. Interestingly, the recovered pitch amusia was related to smaller GMV decreases in the temporoparietal junction whereas the recovered rhythm amusia was associated to smaller GMV decreases in the inferior temporal pole. Overall, the results provide a more comprehensive picture of

  8. Occupationally Acquired American Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Maria Edileuza Felinto de Brito

    2012-01-01

    Full Text Available We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL: one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples and characterized as Leishmania (Viannia naiffi through an indirect immunofluorescence assay (IFA with species-specific monoclonal antibodies (mAbs and by multilocus enzyme electrophoresis (MLEE. Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis.

  9. Naturally acquired immunity to Plasmodium falciparum malaria in Africa

    DEFF Research Database (Denmark)

    Hviid, Lars

    2005-01-01

    Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective...... protective immunity to P. falciparum malaria is acquired following natural exposure to the parasites is beginning to emerge, not least thanks to studies that have combined clinical and epidemiological data with basic immunological research. This framework involves IgG with specificity for clonally variant...... antigens on the surface of the infected erythrocytes, can explain some of the difficulties in relating particular immune responses with specificity for well-defined antigenic targets to clinical protection, and suggests a radically new approach to controlling malaria-related morbidity and mortality...

  10. Recovering With Acquired Apraxia of Speech: The First 2 Years.

    Science.gov (United States)

    Haley, Katarina L; Shafer, Jennifer N; Harmon, Tyson G; Jacks, Adam

    2016-12-01

    This study was intended to document speech recovery for 1 person with acquired apraxia of speech quantitatively and on the basis of her lived experience. The second author sustained a traumatic brain injury that resulted in acquired apraxia of speech. Over a 2-year period, she documented her recovery through 22 video-recorded monologues. We analyzed these monologues using a combination of auditory perceptual, acoustic, and qualitative methods. Recovery was evident for all quantitative variables examined. For speech sound production, the recovery was most prominent during the first 3 months, but slower improvement was evident for many months. Measures of speaking rate, fluency, and prosody changed more gradually throughout the entire period. A qualitative analysis of topics addressed in the monologues was consistent with the quantitative speech recovery and indicated a subjective dynamic relationship between accuracy and rate, an observation that several factors made speech sound production variable, and a persisting need for cognitive effort while speaking. Speech features improved over an extended time, but the recovery trajectories differed, indicating dynamic reorganization of the underlying speech production system. The relationship among speech dimensions should be examined in other cases and in population samples. The combination of quantitative and qualitative analysis methods offers advantages for understanding clinically relevant aspects of recovery.

  11. 7 CFR 3575.90 - Disposition of acquired property.

    Science.gov (United States)

    2010-01-01

    ... property. (a) General. When the lender acquires title to the collateral and the final loss claim is not... 7 Agriculture 15 2010-01-01 2010-01-01 false Disposition of acquired property. 3575.90 Section... protect the collateral, and the lender must dispose of the collateral without delay. (b) Re-title...

  12. Incidence and risk factors for surgically acquired pressure ulcers: a prospective cohort study investigators.

    Science.gov (United States)

    Webster, Joan; Lister, Carolyn; Corry, Jean; Holland, Michelle; Coleman, Kerrie; Marquart, Louise

    2015-01-01

    To assess the incidence of hospital-acquired, surgery-related pressure injury (ulcers) and identify risk factors for these injuries. We used a prospective cohort study to investigate the research question. The study was conducted at a major metropolitan hospital in Brisbane, Australia. Five hundred thirty-four adult patients booked for any surgical procedure expected to last more than 30 minutes were eligible for inclusion. Patients who provided informed consent for study participation were assessed for pressure ulcers, using the European Pressure Ulcer Advisory Panel and National Pressure Ulcer Advisory Panel Guidelines, before entering the operating room and again in the post-anesthetic care unit (PACU). Research nurses and all PACU nurses were trained in skin assessment and in pressure ulcer staging. Patients were not assessed again after their discharge from the PACU. Seven patients (1.3%) had existing pressure injuries (ulcers) and a further 6 (1.3%) developed a surgery-related pressure ulcer. Risk factors associated with surgery-related pressure injuries were similar to non-surgically related risks and included older age, skin condition, and being admitted from a location other than one's own home. Length of surgery was not associated with pressure ulcer development in this cohort. Perioperative nurses play an important role in identifying existing or new pressure injuries. However, many of these nurses are unfamiliar with pressure ulcer classification, so education in this area is essential. Although the incidence of surgically acquired pressure ulcers was low in this cohort, careful skin inspection before and after surgery provides an opportunity for early treatment and may prevent existing lesions progressing to higher stages.

  13. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  14. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  15. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  16. [Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between 2008 and 2015].

    Science.gov (United States)

    Patient, M; Fuseau, P; Deligny, C

    2017-08-01

    Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique. We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st. Diagnosis was confirmed if ADAMTS-13 activity was<10 %. Ten patients were included, corresponding to an average annual incidence of 3.2 cases/year/million individuals. None of the patient presented with the association of the five characteristic features of TTP. Microangiopathic haemolytic anaemia and severe peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to diagnosis. There was no kidney involvement in 90 % of all patients, but severe neurological manifestations occurred in 70 %. Classical management including corticosteroids and plasma exchanges allowed clinical remission in 6 out of the 10 cases. If necessary, rituximab or cyclophosphamide was used. The overall survival rate was 90 %. In Martinique, the incidence of TTP is twice that reported in similar studies in France. Clinical manifestations seem to differ by more common and more severe neurological involvement. Mortality is low, in part, due to optimal care. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  17. Duodenal Tumor Presenting as Acquired Hemophilia in an 88-Year-Old Woman: A Clinical Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2012-01-01

    Full Text Available Acquired hemophilia is a rare disease, presenting with severe hemorrhage, we present a case caused by a duodenal tumor, the clinical management, ethical implications, treatment recommendations, and a review of the literature.

  18. Physical Plant Design and Engineering Controls to Reduce Hospital-Acquired Infections

    Directory of Open Access Journals (Sweden)

    JM Conly

    2006-01-01

    Full Text Available The importance of the environment as a reservoir for microorganisms implicated in disease transmission in the hospital setting has been increasingly recognized, especially with respect to dialysis units, ventilation in specialized areas, and the proper use of disinfectants (1. Inherent within the environmental setting is the importance of physical plant design. Several studies have underscored the importance of optimizing design standards to maximize patient and health care worker (HCW safety, including the prevention of hospital-acquired infections in patients (2-6. Ulrich et al (7 recently completed an evidence-based review, entitled 'The role of the physical environment in the hospital of the 21st century: A once-in-a-lifetime opportunity', for the Center for Health Design in California (USA, which was funded by the Robert Wood Johnson Foundation. Ulrich and colleagues identified over 600 studies that examined the hospital environment and its effects on staff effectiveness, patient safety, patient and family stress, quality and costs. They suggested that one of the important elements in improving patient safety is the reduction of the risk of hospital-acquired infections through improved facility design.

  19. Comparative antimicrobial susceptibility of aerobic and facultative bacteria from community-acquired bacteremia to ertapenem in Taiwan

    Directory of Open Access Journals (Sweden)

    Fung Chang-Phone

    2007-07-01

    -tazobactam, or ciprofloxacin against oxacillin-susceptible S. aureus (17/17, 100%and was more active than any of these agents against enterobacteriaceae (82/82, 100%. Conclusion Based on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.

  20. [Probiotics as an items of increasing the effectiveness of treatment of community-acquired pneumonia in adolescents].

    Science.gov (United States)

    Gonchar, N V; Kassner, L N; Korenev, P B; Il'kovich, Iu M; Mogilina, S V; Petrov, L N

    2011-01-01

    The aim of the work was to evaluate the efficiency of microbial probiotics Vitaflor and metabolic probiotic Aktoflor-C in complex treatment of community-acquired pneumonia in adolescents in a hospital. The observation involved 38 children aged 11 to 18 years with radiologically verified community-acquired pneumonia, including 23 boys and 15 girls. Patients were divided in 3 groups. Patients in group 1 (n = 13) simultaneously with the antibiotic therapy received per os Vitaflor probiotic containing symbiotic strains of Lactobacillus acidophilus; patients in group 2 (n = 10) along with antibiotic therapy received per os metabolic probiotic Aktoflor-C, containing low molecular weight exometabolites bacteria; patient of the comparison group (n = 15) received antibiotic therapy only. The effectiveness of the used treatment schemes was assessed on the dynamics of the gut state microbiot acoarding to an extended bacteriological examination of faecal flora, level of saliva IgA secretory (before and after treatment), the dynamics of SF-36 quality of life 1 month after discharge from hospital. Was conducted a study of economic efficiency of different modes of therapy. Results showed that adolescents with community-acquired pneumonia during standard antibiotic therapy indicated development of dysbiotic bowel disturbances in the form of reliable oppression of the bifidobacteria and laktoflora. Dysbiosis of the microbial associations are not conducive to proper implementation of immune and nutritional functions of the intestine that shows the imperfection of rehabilitation of patients with pneumonia according to the evaluation of SF-36 quality of life. Pharmacoeconomic analysis revealed the benefits of probiotic metabolic type "Aktoflor" used in addition to standard therapy of community-acquired pneumonia in adolescents.

  1. Long-term psychological functioning of adults with severe congenital facial disfigurement.

    Science.gov (United States)

    Versnel, Sarah L; Plomp, Raul G; Passchier, Jan; Duivenvoorden, Hugo J; Mathijssen, Irene M J

    2012-01-01

    In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a non-facially disfigured reference group. Also explored is the extent to which psychological functioning of the congenital group is related to satisfaction with facial appearance, fear of negative appearance evaluation by others, self-esteem, and severity of the facial deformity. Fifty-nine adults with severe congenital facial disfigurement, 59 adults with a traumatically acquired facial deformity in adulthood, and 120 non-facially disfigured adults completed standardized psychological, physical, and demographic questionnaires, including the Fear of Negative Appearance Evaluation Scale, the Rosenberg Self-Esteem Scale, the Hospital Anxiety and Depression Scale, the Achenbach Adult Self-Report, the 36-Item Short-Form Health Survey, and a visual analogue scale. Adults with severe congenital facial disfigurement had relatively normal psychological functioning but appeared more prone to internalizing problems than the non-facially disfigured adults. Compared with patients with an acquired facial deformity, the congenital group displayed fewer problems on the physical component score of quality of life only. Satisfaction with facial appearance, fear of negative appearance evaluation, and self-esteem were good predictors of the different aspects of psychological functioning, with the exception of the physical component score of quality of life. Improving satisfaction with facial appearance (by surgery), enhancing self-esteem, or lowering fear of negative appearance evaluation (by psychological support) may enhance long-term psychological functioning. Future research should focus on the individual patient and risk factors for maladjustment. Risk, II.

  2. Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia.

    Directory of Open Access Journals (Sweden)

    Eusebi Chiner

    Full Text Available We hypothesized that obstructive sleep apnea (OSA can predispose individuals to lower airway infections and community-acquired pneumonia (CAP due to upper airway microaspiration. This study evaluated the association between OSA and CAP.We performed a case-control study that included 82 patients with CAP and 41 patients with other infections (control group. The controls were matched according to age, sex and body mass index (BMI. A respiratory polygraph (RP was performed upon admission for patients in both groups. The severity of pneumonia was assessed according to the Pneumonia Severity Index (PSI. The associations between CAP and the Epworth Sleepiness Scale (ESS, OSA, OSA severity and other sleep-related variables were evaluated using logistic regression models. The associations between OSA, OSA severity with CAP severity were evaluated with linear regression models and non-parametric tests.No significant differences were found between CAP and control patients regarding anthropometric variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals with an Apnea-Hypopnea Index (AHI ≥10, showed an increased risk of CAP (OR = 2·86, 95%CI 1·29-6·44, p = 0·01. Patients with severe OSA (AHI≥30 also had a higher risk of CAP (OR = 3·18, 95%CI 1·11-11·56, p = 0·047. In addition, OSA severity, defined according to the AHI quartile, was also significantly associated with CAP (p = 0·007. Furthermore, OSA was significantly associated with CAP severity (p = 0·0002, and OSA severity was also associated with CAP severity (p = 0·0006.OSA and OSA severity are associated with CAP when compared to patients admitted to the hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of CAP and could have clinical implications. This link between OSA and infection risk should be explored to investigate the

  3. 22 CFR 120.13 - United States.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false United States. 120.13 Section 120.13 Foreign... United States. United States, when used in the geographical sense, includes the several states, the Commonwealth of Puerto Rico, the insular possessions of the United States, the District of Columbia, the...

  4. Short-term outcomes of the surgical management of acquired rectourethral fistulas: does technique matter?

    Directory of Open Access Journals (Sweden)

    Nfonsam VN

    2013-01-01

    Full Text Available Valentine N Nfonsam,1 James JL Mateka,2 Andrew D Prather,2 Jorge E Marcet21Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ, USA; 2Department of Surgery, College of Medicine, University of South Florida, Tampa, FL, USABackground: Acquired rectourethral fistulas are uncommon and challenging to repair. Most arise as a complication of prostate cancer treatment. Several procedures have been described to repair rectourethral fistulas with varying outcomes. We review the etiology, management, and outcomes of patients with rectourethral fistulas at our institution.Materials and methods: A retrospective review of patients undergoing repair of rectourethral fistulas was undertaken. Data were collected on patient demographics, fistula etiology, operative procedure, fecal and urinary diversion, and clinical outcome. Patients with urinary and/or fecal diversion underwent radiographic evaluation to confirm closure of the fistula prior to reversal of the diversion.Results: Fistula repair was performed on 22 patients from 1999 to 2009. All the patients were male of an average age of 69 years (range: 39–82 years. All patients, except one, had prostate cancer. Fistula formation was associated with radiotherapy in 54.4% of patients, brachytherapy in 36.4% of patients, and with external beam radiation therapy in 18.2% of patients. Other causes included prostatectomy (seven patients, 31.8%, cryotherapy (two patients, 9.1%, and perianal abscess (one patient, 4.5%. Procedures performed for fistula repair included transanal repair (eleven patients, 50%, transperineal repair (five patients, 22.7%, transabdominal repair (three patients, 13.6%, and York–Mason repair (three patients, 13.6%. Fourteen patients (63.6% had urinary diversion. Fecal diversion was performed in 16 (72.7% patients. Five (22.7% patients had had previous attempts at fistula repair. Of the 22 patients treated, repair was successful in 20 patients (91%. The average

  5. Long-term psychological functioning of adults with severe congenital facial disfigurement

    NARCIS (Netherlands)

    Passchier, J.; Versnel, S.L.; Plomp, R.G.; Duivenvoorden, H.J.; Mathijssen, I.M.

    2012-01-01

    BACKGROUND: In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a

  6. Disease: H01759 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available eration of anti-F13 antibodies (AHFXIII) is a rare but severe life-threatening bleeding disorder. In contras...t, non-autoimmune hemorrhagic acquired F13 deficiency (HAF13D) is a less severe bleeding...XIII requires immunosuppressive therapy to eradicate autoantibodies in addition to F13 replacement therapy to arrest bleeding

  7. Bacteriological and clinical profile of Community acquired pneumonia in hospitalized patients

    Directory of Open Access Journals (Sweden)

    Shah Bashir

    2010-01-01

    Full Text Available The aim of our study was to obtain comprehensive insight into the bacteriological and clinical profile of community-acquired pneumonia requiring hospitalization. The patient population consisted of 100 patients admitted with the diagnosis of community-acquired pneumonia (CAP, as defined by British Thoracic society, from December 1998 to Dec 2000, at the Sher- i-Kashmir institute of Medical Sciences Soura, Srinagar, India. Gram negative organisms were the commonest cause (19/29, followed by gram positive (10/29. In 71 cases no etiological cause was obtained. Pseudomonas aeruginosa was the commonest pathogen (10/29, followed by Staphylococcus aureus (7/29, Escherichia coli (6/29, Klebsiella spp. (3/29, Streptococcus pyogenes (1/29, Streptococcus pneumoniae (1/29 and Acinetobacter spp. (1/29. Sputum was the most common etiological source of organism isolation (26 followed by blood (6, pleural fluid (3, and pus culture (1. Maximum number of patients presented with cough (99%, fever (95%, tachycardia (92%, pleuritic chest pain (75%, sputum production (65% and leucocytosis (43%. The commonest predisposing factors were smoking (65%, COPD (57%, structural lung disease (21%, diabetes mellitus (13%, and decreased level of consciousness following seizure (eight per cent and chronic alcoholism (one per cent. Fourteen patients, of whom, nine were males and five females, died. Staphylococcus aureus was the causative organism in four, Pseudomonas in two, Klebsiella in one, and no organism was isolated in seven cases. The factors predicting mortality at admission were - age over 62 years, history of COPD or smoking, hypotension, altered sensorium, respiratory failure, leucocytosis, and s0 taphylococcus pneumonia and undetermined etiology. The overall rate of identification of microbial etiology of community-acquired pneumonia was 29%, which is very low, and if serological tests for legionella, mycoplasma and viruses are performed the diagnostic yield would

  8. Acquired factor VII deficiency associated with acute myeloid leukemia.

    Science.gov (United States)

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  9. Use of a bovine genome array to identify new biological pathways for beef marbling in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Lim Da-jeong

    2010-11-01

    Full Text Available Abstract Background Marbling (intramuscular fat is a valuable trait that impacts on meat quality and an important factor determining price of beef in the Korean beef market. Animals that are destined for this high marbling market are fed a high concentrate ration for approximately 30 months in the Korean finishing farms. However, this feeding strategy leads to inefficiencies and excessive fat production. This study aimed to identify candidate genes and pathways associated with intramuscular fat deposition on highly divergent marbling phenotypes in adult Hanwoo cattle. Results Bovine genome array analysis was conducted to detect differentially expressed genes (DEGs in m. longissimus with divergent marbling phenotype (marbling score 2 to 7. Three data-processing methods (MAS5.0, GCRMA and RMA were used to test for differential expression (DE. Statistical analysis identified 21 significant transcripts from at least two data-processing methods (P . All 21 differentially expressed genes were validated by real-time PCR. Results showed a high concordance in the gene expression fold change between the microarrays and the real time PCR data. Gene Ontology (GO and pathway analysis demonstrated that some genes (ADAMTS4, CYP51A and SQLE over expressed in high marbled animals are involved in a protein catabolic process and a cholesterol biosynthesis process. In addition, pathway analysis also revealed that ADAMTS4 is activated by three regulators (IL-17A, TNFα and TGFβ1. QRT-PCR was used to investigate gene expression of these regulators in muscle with divergent intramuscular fat contents. The results demonstrate that ADAMTS4 and TGFβ1 are associated with increasing marbling fat. An ADAMTS4/TGFβ1 pathway seems to be associated with the phenotypic differences between high and low marbled groups. Conclusions Marbling differences are possibly a function of complex signaling pathway interactions between muscle and fat. These results suggest that ADAMTS4

  10. Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria.

    Science.gov (United States)

    Arzanlou, Mohsen; Chai, Wern Chern; Venter, Henrietta

    2017-02-28

    Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. Immunomodulation in community-acquired pneumonia

    NARCIS (Netherlands)

    Remmelts, H.H.F.

    2013-01-01

    Community-acquired pneumonia (CAP) is a common disease with considerable morbidity and mortality, despite effective antibiotic treatment. In this thesis, we showed that the major causative microorganisms in CAP trigger distinct inflammatory response profiles in the host. While an inflammatory

  12. Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy.

    Science.gov (United States)

    Esposito, Susanna; Zampiero, Alberto; Ruggiero, Luca; Madini, Barbara; Niesters, Hubert; Principi, Nicola

    2015-07-01

    An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 OBJECTIVES: To investigate the potential involvement of EV-D68 in determining community-acquired pneumonia (CAP) in hospitalised children in order to acquire information concerning the clinical problems associated with EV-D68 in Italy. This prospective study of children hospitalised for CAP in the largest Pediatric Department in Milan, Italy, was carried out between 1 June and 31 December 2014. All of the children's admission nasopharyngeal swabs were investigated for the presence of EV-D68. One hundred and seventy-six children with radiographically confirmed CAP were hospitalised during the 7-month study period: 97 (55.1%) had enterovirus/rhinovirus-positive nasopharyngeal samples, including four (2.3%) positive for EV-D68. These four samples were collected between 9 and 21 October, a month in which 21 cases of CAP were recorded. Phylogenetic analysis showed that all of the sequences fell into clade B. The most severe case was diagnosed in a 14-year-old girl with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome), who died after 12 days of hospitalisation. EV-D68 was detected in few children with usually mild-to-moderate lower respiratory tract infection, although the disease lead to the death of a girl with a severe chronic underlying disease. Further studies capable of better defining the epidemiological, genetic and pathogenetic characteristics of the virus are required in order to be able to prepare appropriate preventive and therapeutic measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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.

  14. Growth and {delta}{sup 13}C responses to increasing atmospheric carbon dioxide concentrations for several crop species

    Energy Technology Data Exchange (ETDEWEB)

    Hanba, Y.T.; Wada, E. [Center for Ecological Research, Kyoto University, Kyoto (Japan); Osaki, M.; Nakamura, T. [Faculty of Agriculture, Hokkaido University, Hokkaido (Japan)

    1996-04-01

    The responses of plant growth and carbon isotope discrimination ({Delta}) to elevated atmospheric CO{sub 2} concentrations for several crop species (lettuce: Lactuca sativa L.; corn: Zea Mays L. var. P3540, wheat: Triticum aestivum L. var Haruyutaka; and soybean: Glycine Max (L). Merr. var. Kitamusume) were investigated. Shoot relative growth rate was used to indicate plant growth, and {delta}{sup 13}C value of leaf materials in corn (C4 species) was used to calculate {Delta} for C3 species. Plant growth was stimulated by enriched CO{sub 2}, while {Delta} remained almost constant as CO{sub 2} concentration changed. {Delta} showed interspecific difference, and the plant species of larger {Delta} had larger relative growth rates. Relative growth rates of the plants of larger {Delta} were stimulated by CO{sub 2} enrichment more than those of the plants of smaller {Delta}. We propose that plant {Delta} could be a possible parameter to assess the interspecific difference of plant response to the increasing atmospheric CO{sub 2} concentrations. 3 figs., 2 tabs., 25 refs.

  15. Impacts of Mergers and Acquisitions on Acquirer Banks’ Performance

    Directory of Open Access Journals (Sweden)

    Burhan Ali Shah

    2017-09-01

    Full Text Available This study investigates the effects of mergers and acquisitions (M & A on the operating performance of the acquirer banks in Pakistan. For this purpose, a sample of 18 transactions, involving acquirer banks, listed on the Karachi Stock Exchange, is used. The Financial Ratio Analysis (FRA is used to determine the effects of M & A. The significance of change in the operating performances is tested through a paired sample t-test. The results indicate deterioration in the performances of the acquirer banks in the post-merger period.

  16. Characterization of vNr-13, the first alphaherpesvirus gene of the bcl-2 family

    International Nuclear Information System (INIS)

    Aouacheria, Abdel; Banyai, Michelle; Rigal, Dominique; Schmidt, Carl J.; Gillet, Germain

    2003-01-01

    The Bcl-2 family, including antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report the characterization of a new member of the bcl-2 family, encoded by herpesvirus of turkeys (HVT). The product of this gene shares 80% homology with Nr-13, an apoptosis inhibitor, which is overexpressed in avian cells transformed by the v-src oncogene. This new gene, that we propose to call vnr-13, is the first member of the bcl-2 family to be isolated among α-herpesviruses. Results from cells expressing the HVT-vnr-13 gene product show that the encoded protein inhibits apoptosis and also reduces the rate of cellular proliferation. Contrary to all bcl-2 homologues found in γ-herpesvirus, which are intronless, vnr-13 has the same organization as the cellular nr-13 gene. Hence, the HVT vnr-13 gene may have been acquired from a reverse transcriptase product of an unspliced precursor RNA, or via direct recombination with the host chromosomal DNA

  17. Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

    Science.gov (United States)

    Chen, Jiao; Li, Xiaozhong; Bai, Zhenjiang; Fang, Fang; Hua, Jun; Li, Ying; Pan, Jian; Wang, Jian; Feng, Xing; Li, Yanhong

    2016-01-01

    Objective To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis. Methods This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission. Results Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08–1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15–25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65–0.82; P fluid overload were independently associated with PICU mortality in children with severe sepsis. PMID:27467522

  18. Pulmonary infiltrates during community acquired Gram-negative bacteremia

    DEFF Research Database (Denmark)

    Fjeldsøe-Nielsen, Hans; Gjeraa, Kirsten; Berthelsen, Birgitte G

    2013-01-01

    The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark.......The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark....

  19. Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review

    Directory of Open Access Journals (Sweden)

    Nuria Carballo

    2017-03-01

    Full Text Available Introduction: Community-acquired pneumonia (CAP is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. Objective: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. Material and methods: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. Results: A total of 70 articles were found to have been published, 13 (18.8% having been included and 57 (81.4% excluded. Cohort studies were predominant, having totaled 16 in number (20.7% as compared to one sole cross-sectional study (3.5%. Conclusions: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.

  20. Antibiotic stewardship in community-acquired pneumonia.

    Science.gov (United States)

    Viasus, Diego; Vecino-Moreno, Milly; De La Hoz, Juan M; Carratalà, Jordi

    2017-04-01

    Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

  1. MRI of fetal acquired brain lesions

    International Nuclear Information System (INIS)

    Prayer, Daniela; Brugger, Peter C.; Kasprian, Gregor; Witzani, Linde; Helmer, Hanns; Dietrich, Wolfgang; Eppel, Wolfgang; Langer, Martin

    2006-01-01

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images

  2. MRI of fetal acquired brain lesions

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: daniela.prayer@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)

    2006-02-15

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

  3. Increased colon cancer risk after severe Salmonella infection

    OpenAIRE

    Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

  4. Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly

    Science.gov (United States)

    Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica

    2014-01-01

    Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted

  5. Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore

    Science.gov (United States)

    Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

    2016-01-01

    INTRODUCTION Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. METHODS Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. RESULTS Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. CONCLUSION The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. PMID:26805667

  6. Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore.

    Science.gov (United States)

    Loh, Jin Phang; Gao, Qiu Han Christine; Lee, Vernon J; Tetteh, Kevin; Drakeley, Chris

    2016-12-01

    Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries. Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand. Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia. The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore. Copyright: © Singapore Medical Association

  7. Multinational Exploration of Acquired R&D Activities

    DEFF Research Database (Denmark)

    Gammelgaard, Jens

    2004-01-01

    R&D. This paper establishes the connection between amultinational corporation that follows a capability-motivated acquisition strategy and theR&D role new subsidiaries should play in order for the acquired resources to be utilizedcorporation-wide. Statistical findings reveal the need to follow......This paper presents the results of a survey of 54 Danish multinational corporations that haveacquired activities abroad. The role of the acquired R&D units was the focus of the survey,particularly with respect to the schism between basic and applied R&D, and the schismbetween autonomous and network...

  8. A case of acquired port wine stain: an association with repeated sunburn?

    Science.gov (United States)

    Seremet, Sila; Benar, Elif B; Afsar, Fatma Sule; Calli, Aylin; Ulusarac, Ozlem

    2016-10-01

    Unlike congenital port wine stain (PWS), an acquired PWS is a rare vascular lesion that develops later in life. Although solar damage is associated with acquired PWS, there is no reported case of acquired PWS after sunburn in the literature. We report a case of a 54-year-old man diagnosed with acquired PWS possibly caused by repeated sunburn. We recommended laser treatment to our patient; however, the patient did not chose to receive any treatment. Our case demonstrates a possible rare occurrence of an acquired PWS after sunburn with larger lesions and more diffuse distribution. For this reason, our case differs from other acquired PWS cases. © 2016 The International Society of Dermatology.

  9. Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13

    International Nuclear Information System (INIS)

    de Saint Basile, G.; Arveiler, B.; Oberle, I.

    1987-01-01

    The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis

  10. Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis.

    Directory of Open Access Journals (Sweden)

    Jiao Chen

    Full Text Available To evaluate whether early and acquired daily fluid overload (FO, as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis.This study enrolled 202 children in a pediatric intensive care unit (PICU with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission.Of the 202 patients, 61 (30.2% died during PICU stay. Among all patients, 41 (20.3% experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154, 36 (23.4% developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08-1.33; P = 0.001; n = 202 and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15-25.96; P = 0.032; n = 154 were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ≥10%: 4 [3-8], 7 [4-11] vs. 10 [6-16] days; P <0.001; n = 154 and in survivors (4 [3-8], 7 [5-11] vs. 10 [5-15] days; P <0.001; n = 121. Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65-0.82; P <0.001; n = 202 for predicting mortality in patients with severe sepsis, with a sensitivity of 67.2% and a specificity of 80.1% at the

  11. Acquired versus Non-Acquired Subsidiaries - Which Entry Mode do Parent Firms Prefer

    OpenAIRE

    Esther Kalkbrenner

    2010-01-01

    Despite the economic importance of international foreign direct investment (FDI) flows, investment decisions of multinational firms are not well understood. A multinational firm can establish a subsidiary in a foreign country through greenfield investment or through acquiring an existing firm in the target country. The goal of this paper is to shed some light on the determinants of foreign market entry modes. In particular to analyze the systematic variation in the mode choice of FDI, namely ...

  12. The challenge of retaining customers acquired with free trials

    NARCIS (Netherlands)

    Datta, H.; Foubert, B.; van Heerde, H.J.

    Many service firms acquire customers by offering free-trial promotions. A crucial challenge is to retain customers acquired with these free trials. To address this challenge, firms need to understand how free-trial customers differ from regular customers in terms of their decision making to retain

  13. Recurrent and acquired tracheoesophageal fistulae (TEF)-Minimally invasive management.

    Science.gov (United States)

    Nazir, Zafar; Khan, Muhammad Arif Mateen; Qamar, Javaria

    2017-10-01

    Recurrent and acquired fistulae are a serious complication of congenital esophageal atresia and tracheoesophageal fistula (TEF) repair and foreign body ingestion (FBI) (e.g., button battery). We report our experience with a minimally invasive approach to recurrent and acquired TEF. Medical records of patients referred for management of recurrent and acquired TEF between 2003 and 2015 were reviewed retrospectively. Patients underwent endoscopic procedures (de-epithelization of fistulous tract and fibrin tissue adhesive-Tisseel R ) under general anesthesia. Nine children (7 male, 2 female) with age range 3months to 3years (mean 1.5year) were managed. TEF closed spontaneously in four patients, whereas in 5 patients the TEF closed after combined endoscopic procedure. Three patients required repeat endoscopic procedures. Follow-up ranged between 7months to 10years (mean 4.2years). Active observation and repeat combined endoscopic procedures are safe alternatives to open surgical repair of acquired and recurrent TEF. Level IV study. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Common acquired kidney diseases in children

    African Journals Online (AJOL)

    5. Common acquired kidney diseases in children. Examination of the urine is probably the most important investigation ... result from the same streptococcal infection. .... musculoskeletal system. ... Prediction of histopathology from clinical.

  15. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny.

    Science.gov (United States)

    Suda, Kenichi; Mizuuchi, Hiroshi; Maehara, Yoshihiko; Mitsudomi, Tetsuya

    2012-12-01

    Lung cancers that harbor somatic activating mutations in the gene for the epidermal growth factor receptor (EGFR) depend on mutant EGFR for their proliferation and survival; therefore, lung cancer patients with EGFR mutations often dramatically respond to orally available EGFR tyrosine kinase inhibitors (TKIs). However, emergence of acquired resistance is virtually inevitable, thus limiting improvement in patient outcomes. To elucidate and overcome this acquired resistance, multidisciplinary basic and clinical investigational approaches have been applied, using in vitro cell line models or samples obtained from lung cancer patients treated with EGFR-TKIs. These efforts have revealed several acquired resistance mechanisms and candidates, including EGFR secondary mutations (T790M and other rare mutations), MET amplification, PTEN downregulation, CRKL amplification, high-level HGF expression, FAS-NFκB pathway activation, epithelial-mesenchymal transition, and conversion to small cell lung cancer. Interestingly, cancer cells harbor potential destiny and ductility together in acquiring resistance to EGFR-TKIs, as shown in in vitro acquired resistance models. Molecular mechanisms of "reversible EGFR-TKI tolerance" that occur in early phase EGFR-TKI exposure have been identified in cell line models. Furthermore, others have reported molecular markers that can predict response to EGFR-TKIs in clinical settings. Deeper understanding of acquired resistance mechanisms to EGFR-TKIs, followed by the development of molecular target drugs that can overcome the resistance, might turn this fatal disease into a chronic disorder.

  16. Improving free play skills of severely retarded children.

    Science.gov (United States)

    Wehman, P; Marchant, J A

    1978-02-01

    Severely and profoundly retarded children are usually deficient in play skills. Since play facilitates socialization, language, and motor development, it is a vitally improtant skill to acquire. This pilot study examined the effects of a behavioral training program on the autistic, independent, and social types of play of four severely and profoundly retarded children. The training program involved the use of instructions, modeling, physical guidance, and verbal reinforcement. Results indicated that a marked increase in independent and social play occurred with the introduction of the training program with all four children. Occupational therapists can play an increasingly important role in helping educators formulate relevant educational programs for severely retarded children, particularly in the areas of play and motor skill development.

  17. An allele of an ancestral transcription factor dependent on a horizontally acquired gene product.

    Science.gov (United States)

    Chen, H Deborah; Jewett, Mollie W; Groisman, Eduardo A

    2012-01-01

    Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid difference between the PmrA proteins from the human adapted Salmonella enterica serovar Paratyphi B and the broad host range S. enterica serovar Typhimurium rendered transcription of PmrA-activated genes dependent on the PmrD protein in the former but not the latter serovar. Bacteria harboring the serovar Typhimurium allele exhibited polymyxin B resistance under PmrA- or under PmrA- and PmrD-inducing conditions. By contrast, isogenic strains with the serovar Paratyphi B allele displayed PmrA-regulated polymyxin B resistance only when experiencing activating conditions for both PmrA and PmrD. We establish that the two PmrA orthologs display quantitative differences in several biochemical properties. Strains harboring the serovar Paratyphi B allele showed enhanced biofilm formation, a property that might promote serovar Paratyphi B's chronic infection of the gallbladder. Our findings illustrate how subtle differences in ancestral genes can impact the ability of horizontally acquired genes to confer new properties.

  18. 33 CFR 211.2 - Authority to acquire real estate.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

  19. Enhancing Medicares Hospital Acquired Conditions Policy

    Data.gov (United States)

    U.S. Department of Health & Human Services — The current Medicare policy of non-payment to hospitals for Hospital Acquired Conditions (HAC) seeks to avoid payment for preventable complications identified within...

  20. Assesment of Severely ASR Damaged Bridges: From Diagnosis to Structural Effects

    DEFF Research Database (Denmark)

    Barbosa, Ricardo Antonio; Hansen, Søren Gustenhoff; Hansen, Kurt Kielsgaard

    2016-01-01

    documented. The majority of the experimental data are based on relatively small scale laboratory specimens accelerated by various exposure conditions. Research on assessment and influence of severely ASR deterioration on the material properties and residual load carrying capacity of real-life structures...... is unfortunately limited. This paper presents an overview and discussion of the Danish experiences with assessment of the residual load carrying capacity of severely non-shear reinforced ASR damaged bridges. The discussion is supported by experimental data acquired from large scale in-situ tests of three severely...

  1. [Acquired angioedema – clinical characteristic of the patients diagnosed in 2012-2016 with acquired C1 inhibitor deficiency].

    Science.gov (United States)

    Stobiecki, Marcin; Czarnobilska, Ewa; Obtułowicz, Krystyna

    Acquired angioedema is a rare disease caused by a deficiency of C1 esterase inhibitor with recurrent swelling symptoms. It may occur in the course of lymphoproliferative disorders or autoimmune diseases. Symptoms resemble hereditary angioedema, and the only differentiating features is negative family history, late onset of symptoms and accompanying lymphoproliferative disorder. The aim of the study was to analyze the cases of acquired angioedema. The retrospective analysis of 341 patients from the registry of patients with C1 inhibitor deficiency. Results: We identified 4 patients among 119 with HAE (3.57%) diagnosed in this same period of time 2012-2016 who fulfilled the criteria of acquired edema. In two cases the primary reason of angioedema was lymphoproliferive disease, in two monoclonal gammapathy of unknown reason. We analyzed also the results of laboratory tests C4, C1 inhibitor, C1q. In all cases the face was dominated localization. After the treatment of primary lymphoproliferive disease, in two cases, we observed total remission of angioedema. Only one patient with gammapathy require treatment with C1 inhibitor during the attacks. In these case we observed both plasma deriver, and recombinant C1 inhibitor were effective.

  2. Neural basis of acquired amusia and its recovery after stroke

    OpenAIRE

    Sihvonen, A.J.; Ripollés, P.; Leo, V.; Rodríguez-Fornells, Antoni; Soinila, S.; Särkämö, T.

    2016-01-01

    Although acquired amusia is a relatively common disorder after stroke, its precise neuroanatomical basis is still unknown. To evaluate which brain regions form the neural substrate for acquired amusia and its recovery, we performed a voxel-based lesion-symptom mapping (VLSM) and morphometry (VBM) study with 77 human stroke subjects. Structural MRIs were acquired at acute and 6 month poststroke stages. Amusia and aphasia were behaviorally assessed at acute and 3 month poststroke stages using t...

  3. Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy

    International Nuclear Information System (INIS)

    Tomiyasu, Moyoko; Obata, Takayuki; Nishi, Yukio; Nakamoto, Hiromitsu; Nonaka, Hiroi; Takayama, Yukihisa; Autio, Joonas; Ikehira, Hiroo; Kanno, Iwao

    2010-01-01

    To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ( 13 C MRS) with a clinical 3.0 T MR system was performed. Subjects were healthy male volunteers (n = 5) and male type-2 diabetic patients (n = 5). Pre- and during oral glucose tolerance tests (OGTT), 13 C MR spectra without proton decoupling were acquired in a monitoring period of over 6 h, and in total seven spectra were obtained from each subject. For OGTT, 75 g of glucose, including 5 g of [1- 13 C]glucose, was administered. The MR signals of liver [1- 13 C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: ρ = -0.68, p 13 C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, 13 C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

  4. Acquired and introduced macroparasites of the invasive Cuban treefrog, Osteopilus septentrionalis

    Directory of Open Access Journals (Sweden)

    Nicole Ortega

    2015-12-01

    Full Text Available Because shifts in host–parasite relationships can alter host populations, attention should be given to the parasites that introduced species take with them or acquire in their introduced range. The Cuban treefrog, Osteopilus septentrionalis, is a successful invasive species in Florida with its parasites in the native range being well-documented, but there is a void in the literature regarding what parasites were lost or introduced in its expansion. We necropsied 330 O. septentrionalis from Tampa, FL and compared their macroparasites to those of O. septentrionalis in their native range and to the parasites of anurans native to the Tampa, FL area to determine the species O. septentrionalis likely introduced or acquired in Florida. At least nine parasite species (Aplectana sp., Oswaldocruzia lenteixeirai, Cylindrotaenia americana, Physaloptera sp., Rhabdias sp., Centrorhynchus sp., unidentified trematode metacercariae, unidentified larval acuariids, and unidentified pentastomids were isolated. We found no differences in parasite communities of adult male and female frogs, which averaged 19.36 parasite individuals and 1.39 parasite species per adult frog, and had an overall prevalence of 77.52%. Acuariid larvae were likely acquired by O. septentrionalis in FL because they are not found in their native range. O. lenteixeirai was likely introduced because it is commonly reported in O. septentrionalis' native range but has never been reported in FL-native anurans. Aplectana sp. is also likely introduced because it has been reported in several anurans in Cuba but only reported once in Florida. O. septentrionalis tended to harbor fewer of its native parasites in the introduced range, which is consistent with the enemy release hypothesis and potentially creates an immunological advantage for this invasive host. Because native populations can be threatened by introduced parasites, there is a need to further explore the frequency and rate at which

  5. Bacteriology of hospital-acquired infection and antibiotic resistance in a hospital university of Bushehr Port Fatemeh Zahra (s in 2002-2003

    Directory of Open Access Journals (Sweden)

    Katayoon Vahdat

    2005-02-01

    Full Text Available Nosocomial infection is an increasing problem. The global problem of antimicrobial resistance is particularly pressing in developing countries, where the infectious disease burden is high and cost constraints prevent the widespread application of newer, more expensive agents. In a prospective study, 203 consecutive cases with hospital-acquired infection in a university hospital in Bushehr port were evaluated. The most common hospital-acquired infection was urinary (76 cases, conjunctivitis (16 cases, bacteremia (8 cases, meningitis (5 cases, wound (3 cases, empyema (2 cases and peritonitis (1 case. The patients with hospital-acquired infection were from surgical and internal medicine I.C.Us (53.2% & 15.6%, respectively. The most frequent isolated organisms were Pseudomonas aeruginosa (25.6%, Acinetobacter baumannii (19.7%, E. coli (13.3%, Klebsiella pneumoniae (11.3%, Staphylococcus aureus (8.4%, Staphylococcus epidermidis (7.9%, Enterobacter species (7%, Streptococcus species (6.4%, and Proteus mirabilis (0.5%. The most resistant organisms to antimicrobial agents were Acinetobacter baumannii and Pseudomonas aeruginosa 97 & 93.3% of these bacteria were resistant to third generation cephalosporins. The isolated Staphylococcal species were resistant to amikacin (94%. In conclusion, gram negative bacteria were the most common etiologic agent of hospital-acquired infection and had a high level of resistance to amikacin and third generation cephalosporins. Therefore, new therapeutic strategies should be designed to combat these microorganisms.

  6. Facile hydrothermal method synthesis of coralline-like Li1.2Mn0.54Ni0.13Co0.13O2 hierarchical architectures as superior cathode materials for lithium-ion batteries

    International Nuclear Information System (INIS)

    Hou, Xianhua; Huang, Yanling; Ma, Shaomeng; Zou, Xiaoli; Hu, Shejun; Wu, Yuping

    2015-01-01

    Highlights: • A coralline-like Li 1.20 Mn 0.54 Ni 0.13 Co 0.13 O 2 cathode was synthesized by hydrothermal method. • Initial discharge capacity of 250.2 mAh g −1 for the cathode was obtained at 0.1 C. • A high reversible specific capacity of 210.2 mAh g −1 after 100 cycles was acquired. • The high capacity retention of 84.5% was obtained even after 200 cycles at 10 C. - Abstract: A coralline-like lithium-rich layered cathode material with homogeneous composition of Li 1.20 Mn 0.54 Ni 0.13 Co 0.13 O 2 has been successfully synthesized via a facile ethanolamine (EA)-mediated hydrothermal method route, with subsequent calcination at 850 °C. An initial specific discharge capacity of 250.2 mAh g −1 and a reversible specific capacity of 210.2 mAh g −1 after 100 cycles at a constant density of 25 mA g −1 (1 C = 250 mA g −1 ) are acquired. Even at 10 C, it still delivers a discharge capacity of approximately 100 mA h g −1 , thereby indicating its excellent high power performance. The sample also shows enhanced cycling performance with 88.5%, 79.9% and 90.5% of capacity retention after 100 cycles at 0.5, 5 and 10 C rates, respectively. Besides, 84.5% of initial capacity is retained even after 200 cycles at 10 C. Consequently, the fascinating electrochemical performance may facilitate the coralline-like LMNCO composite to be a promising alternative cathode for LIBs with a high application potential

  7. Borrowing and Loan Words: The Lemmatizing of Newly Acquired ...

    African Journals Online (AJOL)

    rbr

    or foreign acquisition. English, for instance, is spoken in many countries on all five continents and is, therefore, able to acquire vocabulary from many lan- guages worldwide. This is coupled with the readiness and the ability of the language to acquire new terminology through borrowing, instead of following the puristic ...

  8. Significance of acquired diverticular disease of the vermiform appendix

    DEFF Research Database (Denmark)

    Kallenbach, Klaus; Hjorth, Sofie Vetli; Engel, Ulla

    2012-01-01

    To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms.......To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms....

  9. Significance of anaerobes and oral bacteria in community-acquired pneumonia.

    Directory of Open Access Journals (Sweden)

    Kei Yamasaki

    Full Text Available BACKGROUND: Molecular biological modalities with better detection rates have been applied to identify the bacteria causing infectious diseases. Approximately 10-48% of bacterial pathogens causing community-acquired pneumonia are not identified using conventional cultivation methods. This study evaluated the bacteriological causes of community-acquired pneumonia using a cultivation-independent clone library analysis of the 16S ribosomal RNA gene of bronchoalveolar lavage specimens, and compared the results with those of conventional cultivation methods. METHODS: Patients with community-acquired pneumonia were enrolled based on their clinical and radiological findings. Bronchoalveolar lavage specimens were collected from pulmonary pathological lesions using bronchoscopy and evaluated by both a culture-independent molecular method and conventional cultivation methods. For the culture-independent molecular method, approximately 600 base pairs of 16S ribosomal RNA genes were amplified using polymerase chain reaction with universal primers, followed by the construction of clone libraries. The nucleotide sequences of 96 clones randomly chosen for each specimen were determined, and bacterial homology was searched. Conventional cultivation methods, including anaerobic cultures, were also performed using the same specimens. RESULTS: In addition to known common pathogens of community-acquired pneumonia [Streptococcus pneumoniae (18.8%, Haemophilus influenzae (18.8%, Mycoplasma pneumoniae (17.2%], molecular analysis of specimens from 64 patients with community-acquired pneumonia showed relatively higher rates of anaerobes (15.6% and oral bacteria (15.6% than previous reports. CONCLUSION: Our findings suggest that anaerobes and oral bacteria are more frequently detected in patients with community-acquired pneumonia than previously believed. It is possible that these bacteria may play more important roles in community-acquired pneumonia.

  10. Comprehensive oral-health assessment of individuals with acquired brain-injury in neuro-rehabilitation setting.

    Science.gov (United States)

    Kothari, Mohit; Spin-Neto, Rubens; Nielsen, Jørgen Feldbæk

    2016-01-01

    To perform a detailed clinical oral health assessment and oral-health-related social and behavioural aspect assessment in individuals with acquired brain injury (ABI). Prospective observational study. Thirteen individuals with ABI were recruited. Individual's social and behavioural history, bed-side oral examination score (BOE), tooth condition and periodontal status (bleeding, plaque and clinical attachment loss) were thoroughly examined. The entire examination took up to 60 minutes, using proper dental armamentarium. All evaluated individuals were diagnosed with chronic generalized periodontitis. A relationship between active periodontal disease and severe BOE score was observed (p = 0.01). Significant interaction between severe BOE scores (≥ 15 or ≥ 14) and periodontal disease severity of ≥ 2 mm (p = 0.01) was observed. The same interaction was seen between severe BOE scores and the combination of 75% extent and 2 mm severity (p = 0.01). Severity and activity of periodontitis showed dependence on individual brushing frequency (p = 0.03 and p = 0.05, respectively). Individuals with ABI had a poor status across a range of oral-, dental- and periodontal-related parameters. Further structured studies are required to define evidence-based assessment approaches for such clinical reality.

  11. Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance.

    Directory of Open Access Journals (Sweden)

    Courtney M Yuen

    Full Text Available BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14 adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90 adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83. CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

  12. 45 CFR 7.4 - Option to acquire foreign rights.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Option to acquire foreign rights. 7.4 Section 7.4... Option to acquire foreign rights. In any case where it is determined that all domestic rights should be...-wide regulations issued thereunder, that the Government shall reserve an option to require the...

  13. 34 CFR 7.4 - Option to acquire foreign rights.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Option to acquire foreign rights. 7.4 Section 7.4 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.4 Option to acquire... issued thereunder, that the Government shall reserve an option to require the assignment of such rights...

  14. Treatment of reperfusion injury with recombinant ADAMTS13 in a porcine model of acute myocardial infarction

    NARCIS (Netherlands)

    Eerenberg, E.S.; Teunissen, P.F.A.; Van Den Born, B.J.; Meijers, J.C.; Hollander, M.; Aly, M.; Niessen, H.W.M.; Kamphuisen, P.W.; Levi, M.; Van Royen, N.

    Background: No reflow and decreased microvascular perfusion after percutaneous coronary intervention increase morbidity and mortality in ST-elevation myocardial infarction (STEMI) patients. No reflow may be mediated by platelet vessel wall interaction that is governed by von Willebrand factor.

  15. Effectiveness of a Very Early Stepping Verticalization Protocol in Severe Acquired Brain Injured Patients: A Randomized Pilot Study in ICU.

    Directory of Open Access Journals (Sweden)

    Giuseppe Frazzitta

    Full Text Available Verticalization was reported to improve the level of arousal and awareness in patients with severe acquired brain injury (ABI and to be safe in ICU. We evaluated the effectiveness of a very early stepping verticalization protocol on their functional and neurological outcome.Consecutive patients with Vegetative State or Minimally Conscious State were enrolled in ICU on the third day after an ABI. They were randomized to undergo conventional physiotherapy alone or associated to fifteen 30-minute sessions of verticalization, using a tilt table with robotic stepping device. Once stabilized, patients were transferred to our Neurorehabilitation unit for an individualized treatment. Outcome measures (Glasgow Coma Scale, Coma Recovery Scale revised -CRSr-, Disability Rating Scale-DRS- and Levels of Cognitive Functioning were assessed on the third day from the injury (T0, at ICU discharge (T1 and at Rehab discharge (T2. Between- and within-group comparisons were performed by the Mann-Whitney U test and Wilcoxon signed-rank test, respectively.Of the 40 patients enrolled, 31 completed the study without adverse events (15 in the verticalization group and 16 in the conventional physiotherapy. Early verticalization started 12.4±7.3 (mean±SD days after ABI. The length of stay in ICU was longer for the verticalization group (38.8 ± 15.7 vs 25.1 ± 11.2 days, p = 0.01, while the total length of stay (ICU+Neurorehabilitation was not significantly different (153.2 ± 59.6 vs 134.0 ± 61.0 days, p = 0.41. All outcome measures significantly improved in both groups after the overall period (T2 vs T0, p<0.001 all, as well as after ICU stay (T1 vs T0, p<0.004 all and after Neurorehabilitation (T2 vs T1, p<0.004 all. The improvement was significantly better in the experimental group for CRSr (T2-T0 p = 0.033, T1-T0 p = 0.006 and (borderline for DRS (T2-T0 p = 0.040, T1-T0 p = 0.058.A stepping verticalization protocol, started since the acute stages, improves the

  16. Severe psychogenic tremor of both wrists in a 13-year-old girl treated successfully with a customized wrist brace: a case report

    Directory of Open Access Journals (Sweden)

    Schafflhuber Caroline

    2011-04-01

    Full Text Available Abstract Introduction Psychogenic movement disorders in childhood have been little researched. As there are few courses of treatment which have been evaluated, further examination and case studies about the treatment and clinical course of this rare occurrence of severe psychogenic tremor in childhood and adolescence are much needed. Case presentation A 13-year-old Caucasian girl with tremor in both wrists, severe enough to prevent her from attending school, was sent to our hospital. After a complete neurological and psychiatric examination, in-patient child-psychotherapeutic treatment was started, with careful consideration given to both chronic and acute stress factors which constitute her performance and exam anxiety in school as well as the girl's parents' conflicted relationship. With the aid of a customized wrist brace our patient was able to go to school and write despite the presence of a marked tremor, which in turn reduced her avoidance behavior and exam anxiety. By the end of her in-patient treatment, the tremor was still noticeable, but markedly reduced in severity (reduction 80%. Two weeks after she was discharged from hospital, the tremor had completely disappeared. Conclusion After careful clinical diagnostics, this kind of dissociative disorder should be treated appropriately with age-adapted cognitive-behavioral therapy to achieve positive and lasting benefits.

  17. Comparative dermatology: acquired digital fibrokeratoma

    OpenAIRE

    Cunha Filho, Roberto Rheingantz da

    2008-01-01

    Demonstra-se quadro característico de fibroqueratoma digital adquirido em trabalhadora rural de 42 anos de idade, que se compara a corno de rinoceronte.It is presented a case of a 42 year-old white female farmer with the classical feature of acquired digital fibrokeratoma, which is compared to rhinoceros horn.

  18. REVIEW OF A CASE OF CHILD WITH ACQUIRED APHASIA

    Directory of Open Access Journals (Sweden)

    Silvana FILIPOVA

    2004-12-01

    Full Text Available Achieved children speech disabilities are manifested at certain level of development of speech from the age of 3 to 12 years. The speech disabilities with children from the age of one to three years have developmental and acquired characteristics. It is well-known when and why the disabilities occurr at acquired aphasia or disphasia.The child with acquired aphasia or disphasia has early brain impairements and a relative improvement happens with adequate treatment and prompt rehabilitation treatment. It is more obvious with children than with adults.This fast and complete rehabilitation happens due to the plastic character of child’s brain and the possibilities for intro-hemisphere and inter-hemisphere reorganization of speech functions in childhood.

  19. Residual Activity Correction in Quantitative Myocardial Perfusion N-13-Ammonia PET Imaging : A Study in Post-MI Patients

    NARCIS (Netherlands)

    Markousis-Mavrogenis, George; Juarez-Orozco, Luis Eduardo; Alexanderson, Erick

    2017-01-01

    Background/Introduction/Aim: Positron emission tomography (PET) is the gold standard for the quantification of myocardial blood flow (MBF). A standard PET scan is acquired in two phases (rest and pharmacological stress). N-13-ammonia is a perfusion radiotracer that may show residual activity, which

  20. Acquired epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Maricel Sucar Batista

    2015-12-01

    Full Text Available Epidermolysis bullosa is a group of diseases or skin disorders genetically transmitted and it is characterized by the appearance of bullae, ulcers and skin wounds. It usually appears at birth or in the first months of life. This is a case of a 72-year-old female patient who comes to the dermatology department with skin lesions of 6 months of evolution. A skin biopsy was performed, taking a sample for direct and indirect immunofluorescence. Acquired epidermolysis bullosa of unknown etiology was diagnosed. Treatment was started with low-dose colchicine to increase it later, according to the patient’s tolerance and disease progression.

  1. Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study.

    Directory of Open Access Journals (Sweden)

    Maliwan Hongsuwan

    Full Text Available Little is known about the epidemiology of nosocomial bloodstream infections in public hospitals in developing countries. We evaluated trends in incidence of hospital-acquired bacteremia (HAB and healthcare-associated bacteremia (HCAB and associated mortality in a developing country using routinely available databases.Information from the microbiology and hospital databases of 10 provincial hospitals in northeast Thailand was linked with the national death registry for 2004-2010. Bacteremia was considered hospital-acquired if detected after the first two days of hospital admission, and healthcare-associated if detected within two days of hospital admission with a prior inpatient episode in the preceding 30 days.A total of 3,424 patients out of 1,069,443 at risk developed HAB and 2,184 out of 119,286 at risk had HCAB. Of these 1,559 (45.5% and 913 (41.8% died within 30 days, respectively. Between 2004 and 2010, the incidence rate of HAB increased from 0.6 to 0.8 per 1,000 patient-days at risk (p<0.001, and the cumulative incidence of HCAB increased from 1.2 to 2.0 per 100 readmissions (p<0.001. The most common causes of HAB were Acinetobacter spp. (16.2%, Klebsiella pneumoniae (13.9%, and Staphylococcus aureus (13.9%, while those of HCAB were Escherichia coli (26.3%, S. aureus (14.0%, and K. pneumoniae (9.7%. There was an overall increase over time in the proportions of ESBL-producing E. coli causing HAB and HCAB.This study demonstrates a high and increasing incidence of HAB and HCAB in provincial hospitals in northeast Thailand, increasing proportions of ESBL-producing isolates, and very high associated mortality.

  2. Monitoring severe accidents using AI techniques

    Energy Technology Data Exchange (ETDEWEB)

    No, Young Gyu; Ahn, Kwang Il [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Ju Hyun; Na, Man Gyun [Dept. of Nuclear Engineering, Chosun University, Gwangju (Korea, Republic of); Lim, Dong Hyuk [Korea Institute of Nuclear Nonproliferation and Control, Daejon (Korea, Republic of)

    2012-05-15

    After the Fukushima nuclear accident in 2011, there has been increasing concern regarding severe accidents in nuclear facilities. Severe accident scenarios are difficult for operators to monitor and identify. Therefore, accurate prediction of a severe accident is important in order to manage it appropriately in the unfavorable conditions. In this study, artificial intelligence (AI) techniques, such as support vector classification (SVC), probabilistic neural network (PNN), group method of data handling (GMDH), and fuzzy neural network (FNN), were used to monitor the major transient scenarios of a severe accident caused by three different initiating events, the hot-leg loss of coolant accident (LOCA), the cold-leg LOCA, and the steam generator tube rupture in pressurized water reactors (PWRs). The SVC and PNN models were used for the event classification. The GMDH and FNN models were employed to accurately predict the important timing representing severe accident scenarios. In addition, in order to verify the proposed algorithm, data from a number of numerical simulations were required in order to train the AI techniques due to the shortage of real LOCA data. The data was acquired by performing simulations using the MAAP4 code. The prediction accuracy of the three types of initiating events was sufficiently high to predict severe accident scenarios. Therefore, the AI techniques can be applied successfully in the identification and monitoring of severe accident scenarios in real PWRs.

  3. Monitoring severe accidents using AI techniques

    International Nuclear Information System (INIS)

    No, Young Gyu; Ahn, Kwang Il; Kim, Ju Hyun; Na, Man Gyun; Lim, Dong Hyuk

    2012-01-01

    After the Fukushima nuclear accident in 2011, there has been increasing concern regarding severe accidents in nuclear facilities. Severe accident scenarios are difficult for operators to monitor and identify. Therefore, accurate prediction of a severe accident is important in order to manage it appropriately in the unfavorable conditions. In this study, artificial intelligence (AI) techniques, such as support vector classification (SVC), probabilistic neural network (PNN), group method of data handling (GMDH), and fuzzy neural network (FNN), were used to monitor the major transient scenarios of a severe accident caused by three different initiating events, the hot-leg loss of coolant accident (LOCA), the cold-leg LOCA, and the steam generator tube rupture in pressurized water reactors (PWRs). The SVC and PNN models were used for the event classification. The GMDH and FNN models were employed to accurately predict the important timing representing severe accident scenarios. In addition, in order to verify the proposed algorithm, data from a number of numerical simulations were required in order to train the AI techniques due to the shortage of real LOCA data. The data was acquired by performing simulations using the MAAP4 code. The prediction accuracy of the three types of initiating events was sufficiently high to predict severe accident scenarios. Therefore, the AI techniques can be applied successfully in the identification and monitoring of severe accident scenarios in real PWRs.

  4. Innate-Type and Acquired-Type Allergy Regulated by IL-33

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    Tomohiro Yoshimoto

    2014-01-01

    Full Text Available We propose two types of allergic response: IgE-dependent and IgE-independent, and designate these as 'acquired-type allergy' and 'innate-type allergy', respectively. IL-33 stimulates both innate (basophils, mast cells, or group 2 innate lymphoid cells and acquired (Th2 cells allergy-related cells to induce and/or augment Th2 cytokine production, which leads to eosinophilic inflammation in vivo. Thus, IL-33 is an essential regulator for both 'innate-type allergy' and 'acquired-type allergy', and might be an attractive therapeutic target for allergic diseases.

  5. Pennzoil to acquire part of Chevron's production

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that Pennzoil Co., Houston, will exchange 48% of its $2.2 billion investment in Chevron Corp. for a chunk of chevron's U.S. producing leases. The trade is to involve a tax free exchange of 15.75 million chevron Corp. shares held by Pennzoil for all the stock of Chevron PBC Inc., a Chevron unit owning Gulf of Mexico, Gulf Coast, Permian basin, and other U.S. oil and gas producing leases. Sixty percent of the acquired reserves are in the Gulf of Mexico and Gulf Coast where Pennzoil's operations are concentrated, and 60% of the acquired reserves consist of natural gas, mirroring Pennzoil's reserve ratios

  6. Community-acquired respiratory infections are common in patients with non-Hodgkin lymphoma and multiple myeloma.

    Science.gov (United States)

    Lavi, Noa; Avivi, Irit; Kra-Oz, Zipora; Oren, Ilana; Hardak, Emilia

    2018-07-01

    Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis. Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed. One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated. Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

  7. Efficacy of a Micro-Prompting Technology in Reducing Support Needed by People With Severe Acquired Brain Injury in Activities of Daily Living: A Randomized Control Trial.

    Science.gov (United States)

    OʼNeill, Brian; Best, Catherine; OʼNeill, Lauren; Ramos, Sara D S; Gillespie, Alex

    2017-11-29

    To evaluate the effectiveness of an automated interactive prompting technology in supporting the morning routine of persons with acquired brain injury. The morning routine included maintaining personal hygiene and dressing. An inpatient neurorehabilitation hospital. Persons with acquired brain injury who required prompting when following their morning routine (n = 24), but were not limited by physical disability or dysphasia, took part in the study. Participants (67% with traumatic brain injury) had impairment on indices of memory and executive function. A randomized control trial evaluated the effect of an automated interactive micro-prompting device on the number of prompts by trained staff required for successful completion of the morning routine. Study-specific checklists assessed sequence performance, errors, and verbal prompts required over baseline, rehabilitation as usual, intervention, and return to baseline conditions. The intervention significantly reduced the support required to complete the task compared with usual rehabilitation. Micro-prompting technology is an effective assistive technology for cognition, which reduces support needs in people with significant cognitive impairments.

  8. [Community-acquired pneumonia due to Legionella pneumophila serogroup 1. Study of 97 cases].

    Science.gov (United States)

    Benito, José Ramón; Montejo, José Miguel; Cancelo, Laura; Zalacaín, Rafael; López, Leyre; Fernández Gil de Pareja, Joaquín; Alonso, Eva; Oñate, Javier

    2003-10-01

    Legionella pneumophila is the causal agent of 5% to 12% of sporadic community-acquired pneumonia cases, though rates are changing with the use of new diagnostic methods. This is a retrospective study of all patients admitted to our hospital with community-acquired pneumonia due to Legionella pneumophila between 1997 and 2001. Diagnostic criteria included either a positive Legionella serogroup 1 urinary antigen test or seroconversion and a chest radiograph consistent with pneumonia. A total of 97 patients were studied. Ninety cases (92.8%) were community-acquired and 7 (7.2%) were associated with travelling. In 82 cases (84.5%) the presentation was sporadic. Seventy-five patients were smokers (77.3%). The most common symptoms were fever in 91 patients (93.8%) and cough in 67 (68.1%). In five patients (5.2%) creatine phosphokinase concentrations were over 5 times their baseline values (in two over 100 times); four of these patients presented acute renal failure. Seroconversion was observed in 23/42 patients (54.8%). There were no statistically significant differences between the administration of erythromycin or clarithromycin in monotherapy, or in combination with rifampin. Nineteen patients (19.6%) presented acute renal failure and mechanical ventilation was necessary in 22 (22.7%). Twelve patients died (12.5%). Independent prognostic factors associated with death included respiratory rate > 30 breaths/min, urea > 60 mg/dL and PaO2 scale scores and the presence of complications or mortality. The Legionella urinary antigen test permits early diagnosis and treatment of this disease. The severity scale is an indicator of complications or death.

  9. Alobar holoprosencephaly and Trisomy 13 (Patau syndrome

    Directory of Open Access Journals (Sweden)

    Andressa Dias Costa

    2013-06-01

    Full Text Available Holoprosencephaly (HPE is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central theme of this report, was evident. The most common nonrandom chromosomal abnormality in patients with HPE is trisomy 13. The most severe variant, namely alobar HPE, is shown in this case report. Discussion on this severe anomaly, along with the case report with details of Patau’s syndrome, is the goal of this report.

  10. Acquired hemophilia A: a review of recent data and new therapeutic options.

    Science.gov (United States)

    Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

    2017-10-01

    Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

  11. Acquiring Customers via Word-of-Mouth Referrals : A Virtuous Strategy?

    NARCIS (Netherlands)

    Pieters, Constant; Lemmens, Aurélie

    2015-01-01

    Managers are increasingly using word-of-mouth (WOM) acquisition strategies, such as seeded WOM or referral programs, to acquire new customers. These strategies have proven successful in recruiting customers with higher margin and lower churn probability compared to customers acquired otherwise.

  12. Case Report: Severe Imported Influenza Infections Developed during Travel in Reunion Island.

    Science.gov (United States)

    Allyn, Jérôme; Brottet, Elise; Antok, Emmanuel; Dangers, Laurence; Persichini, Romain; Coolen-Allou, Nathalie; Roquebert, Bénédicte; Allou, Nicolas; Vandroux, David

    2017-12-01

    We report two cases of severe influenza infection imported by tourist patients from their country of origin and developed during travel. While studies have reported cases of influenza infections acquired during travel, here we examine two cases of severe influenza infection contracted in the country of origin that led to diagnosis and therapeutic problems in the destination country. No international recommendation exists concerning influenza vaccination before travel, and few countries recommend it for all travelers. Our study suggests that travel should be canceled when infectious signs are observed before departure. Influenza is a very common infection that is often benign, but sometimes very severe. The most severe cases include shock, acute respiratory distress syndrome (ARDS), myocarditis, rhabdomyolysis, and multiple organ failure. Management can require exceptional therapies, such as extracorporeal membrane oxygenation. A number of studies have focused on influenza infection in travelers. Cases of influenza acquired during travel have been reported in this literature, but no study has examined cases of influenza imported from the country of origin and developed while abroad. The latter situation may lead to 1) diagnostic problems during the nonepidemic season or in places where diagnostic techniques are lacking and 2) therapeutic difficulties resulting from the unavailability of techniques for the management of severe influenza infection in tourist areas. Here, we report two cases of extremely severe influenza infection imported by tourists from their country of origin and developed during travel.

  13. [Community-acquired Acinetobacter pneumonia].

    Science.gov (United States)

    Bernasconi, E; Wüst, J; Speich, R; Flury, G; Krause, M

    1993-08-21

    We report the history of a 38-year-old male native of Sri Lanka admitted to the emergency ward because of chest pain and shortness of breath. On physical and radiographic examination a bilateral predominantly right-sided pneumonia was found. The patient was admitted to the medical ICU and an antibiotic regimen with amoxicillin/clavulanic acid and erythromycin was initiated. Shortly afterwards septic shock developed. The patient was intubated and received high doses of catecholamines. He died 30 hours after admission to the hospital. Cultures from sputum, tracheal aspirate and blood grew Acinetobacter baumanni. Acinetobacter is an ubiquitous gram-negative rod with coccobacillary appearance in clinical specimens, that may appear gram-positive due to poor discoloration on Gram-stain. It is a well known causative agent of nosocomial infections, particularly in intensive care units. Community-acquired pneumonias, however, are quite rare. Sporadic cases have been reported from the US, Papua-New Guinea and Australia. Interestingly, these pneumonias are fulminant and have a high mortality. Chronic obstructive lung disease, diabetes, and tobacco and alcohol consumption appear to be predisposing factors. Due to the rapid course and poor prognosis, prompt diagnosis and adequate antibiotic treatment are indicated. Antibiotics use for community-acquired pneumonias, such as amoxicillin/clavulanic acid or macrolides, are not sufficient. Appropriate antibiotics for the initial treatment of suspected Acinetobacter infections include imipenem and carboxy- and ureidopenicillins combined with an aminoglycoside.

  14. Usefulness of CURB-65 and pneumonia severity index for influenza A H1N1v pneumonia.

    Science.gov (United States)

    Estella, A

    2012-01-01

    Usefulness of CURB-65 and pneumonia severity index for influenza A H1N1v pneumonia. A. Estella. Different prognostic scales have been documented to assess the severity and indications for hospitalization and ICU admissions of community acquired pneumonia. During the past two years Influenza A H1N1v infections have been commonly attended to in emergency departments. The aim of the study was to analyse the usefulness of the application of the Pneumonia Severity Index (PSI) and CURB-65 prognostic scales in patients with primary viral pneumonia caused by influenza A H1N1v. A retrospective study was performed at a community hospital with a 17 bed-intensive care unit. Patients admitted in hospital with influenza A H1N1v pneumonia over a two year period were analysed. CURB 65 and PSI scales were applied in the emergency department and outcome and destination of admission were analysed. 24 patients were registered, 19 required ICU admission and 5 patients were admitted in medical wards. Most of the patients admitted to the intensive care unit (78.9%) required mechanical ventilation. Mortality was 21.1%. Most patients admitted to the ICU had CURB 65 scale of 1 (60%), 13.3% obtained 0 and 26.7% 2. PSI scale resulted class I in a 20%, class II 40%, 26.7% class IV and 13.3% class V. The scales CURB 65 and PSI showed no differences in scores according to the destination of admission and mortality. Use of CURB-65 and PSI in the emergency department may underestimate the risk of patients with Influenza A H1N1v pneumonia. Based in our results, the ability of these scales to predict ICU admissions for Influenza A H1N1v pneumonia is questioned.

  15. Genetic engineering and therapy for inherited and acquired cardiomyopathies.

    Science.gov (United States)

    Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

    2006-10-01

    The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

  16. Influence of sensation seeking on response to alcohol versus placebo: implications for the acquired preparedness model.

    Science.gov (United States)

    Scott, Caitlin; Corbin, William R

    2014-01-01

    Previous research has identified several aspects of behavioral undercontrol that are associated with heavy drinking and problems. Further, research on the acquired preparedness model (Smith and Anderson, 2001) has identified biased learning as a potential mechanism of these effects. Traits like sensation seeking have been linked to stronger positive and weaker negative expectancies, which, in turn, contribute to increased risk for heavy drinking and problems. Although expectancies are thought to represent potentially biased expectations about drinking outcomes, they may also reflect individual differences in alcohol response. The present study examined the strength of associations between sensation seeking and both expectancies (response to placebo) and subjective response under alcohol. Using a between-subjects design, young adult social drinkers (N = 236) were randomly assigned to receive alcohol (target breath alcohol concentration of .08%) or placebo, after which they reported on subjective experiences of stimulation and sedation. Sensation seeking was significantly related to stimulant response, and the strength of this association did not differ by beverage condition (alcohol vs. placebo). The findings argue against a pharmacological explanation for results of prior studies of the acquired preparedness model and support a biased learning interpretation of relations between sensation seeking and positive expectancies. Results also extend the findings on the acquired preparedness model to an implicit measure of positive alcohol expectancies (subjective response to placebo). Future studies using additional measures of implicit expectancies (e.g., Implicit Association Test) would be helpful in determining the relative strength of implicit and explicit expectancies as mediators within the acquired preparedness model.

  17. Clustering and Filtering Tandem Mass Spectra Acquired in Data-Independent Mode

    Science.gov (United States)

    Pak, Huisong; Nikitin, Frederic; Gluck, Florent; Lisacek, Frederique; Scherl, Alexander; Muller, Markus

    2013-12-01

    Data-independent mass spectrometry activates all ion species isolated within a given mass-to-charge window ( m/z) regardless of their abundance. This acquisition strategy overcomes the traditional data-dependent ion selection boosting data reproducibility and sensitivity. However, several tandem mass (MS/MS) spectra of the same precursor ion are acquired during chromatographic elution resulting in large data redundancy. Also, the significant number of chimeric spectra and the absence of accurate precursor ion masses hamper peptide identification. Here, we describe an algorithm to preprocess data-independent MS/MS spectra by filtering out noise peaks and clustering the spectra according to both the chromatographic elution profiles and the spectral similarity. In addition, we developed an approach to estimate the m/z value of precursor ions from clustered MS/MS spectra in order to improve database search performance. Data acquired using a small 3 m/z units precursor mass window and multiple injections to cover a m/z range of 400-1400 was processed with our algorithm. It showed an improvement in the number of both peptide and protein identifications by 8 % while reducing the number of submitted spectra by 18 % and the number of peaks by 55 %. We conclude that our clustering method is a valid approach for data analysis of these data-independent fragmentation spectra. The software including the source code is available for the scientific community.

  18. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

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

  19. Atmospheric CO2 concentrations and (delta)13C values across the Antarctic Circumpolar Current between New Zealand and Antarctica

    International Nuclear Information System (INIS)

    Longinelli, Antonio; Selmo, Enricomaria; Giglio, Federico; Langone, Leonardo; Lenaz, Renzo; Ori, Carlo

    2007-01-01

    Measurements of atmospheric CO 2 concentrations were repeatedly carried out on the vessel 'Italica' of the Italian National Research Program in Antarctica, during cruises from Italy to Antarctica. Discrete air samples were also collected in 4-L Pyrex flasks during these cruises in order to carry out (delta) 13 C analyses on atmospheric CO 2 . The results acquired between New Zealand and Antarctica are reported here. The mean growth rate of the CO 2 concentration from 1996 to 2003 in this area of the Southern Oceans is of about 1.8 ppmv/yr, in good agreement with NOAA/CMDL measurements. The rates of increase from cruise to cruise are rather variable. From 1996-1997 to 1998-1999 cruise the yearly growth rate is 2.75 ppmv/yr, close to the large growth rates measured in several areas and mainly related to the most severe El Nino event of the last years. The other yearly growth rates are of about 1.3 and 2 ppmv for the periods 1998-1999 to 2001-2002 and 2001-2002 to 2003-2004, respectively. The large difference between these two values is probably related to the uncertainty on the only two 2001-2002 discrete measurements of CO 2 concentration in this area. The measured (delta) 13 C values show two completely different distributions and a large interannual variability. The 1998-1999, 2002-2003, and 2003-2004 results obtained between about 55 deg S and 65 deg S across the Antarctic Polar Front show a marked negativization of up to more than 0.2% when compared to the background values. The results are related to local source regions of CO 2 , as frequently found in the Southern Ocean by several authors; the negative (delta) 13 C values are tentatively related to the possible contribution of different causes. Among them, the southward negative gradient of (delta) 13 C of the dissolved inorganic carbon, the contribution from upwelling deep waters and from subsurface processes between the Northern SubAntarctic Front and the Polar Front, and, partly, the contribution of CO 2

  20. Adynamic Graciloplasty With a Pedicled Gracilis Muscle Flap Wrapped Around Bulbar Urethra for Treatment of Male Acquired Urinary Incontinence.

    Science.gov (United States)

    Guo, Hailin; Sa, Yinglong; Xu, Yuemin; Wang, Lin; Fei, Xiaofang

    2016-05-01

    To evaluate the efficacy of adynamic gracilis urethral myoplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra for treatment of male acquired urinary incontinence. Twenty-four patients with acquired urinary incontinence (8 after radical prostatectomy, 7 after transurethral resection of the prostate, and 9 after posterior urethroplasty) were included in our study. Eighteen of these patients (75.0%) had mild to moderate urinary incontinence, and 6 (25.0%) had severe urinary incontinence. All patients received adynamic gracilis urethral myoplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra and had a close follow-up. The mean postoperative maximum urethral pressure after the gracilis muscle wrapped around bulbar urethra was significantly higher than that of the preoperative measurements (P urethra can raise the urethral pressure. Adynamic graciloplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra is a safe and effective surgical option in the treatment of male patients with mild to moderate incontinence, but is not suitable for severe incontinence. Copyright © 2016 Elsevier Inc. All rights reserved.