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Sample records for early myelofibrosis causing

  1. Extramedullary hemopoiesis with undiagnosed, early myelofibrosis causing spastic compressive myelopathy: Case report and review

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    Dewan Udita

    2010-01-01

    Full Text Available Extramedullary hemopoiesis (EMH is a common compensatory phenomenon associated with chronic hemolytic anemia. Abnormal hemopoietic tissue usually develops in sites responsible for fetal hemopoiesis, such as spleen, liver and kidney; however, other regions such as the spine may also become involved. In this study, a patient presenting with spastic paraparesis due to EMH in the dorsal spine is described. A 62-year-old man presented with paraparesis. Magnetic resonance imaging revealed a large lesion involving the T2-L2 vertebral levels with a large extradural component causing thecal sac compression. Laminectomy with excision of mass was carried out. The histopathology revealed EMH. The patient had no known cause for EMH at the time of diagnosis but, subsequently, a bone marrow examination revealed early myelofibrosis. This case represents the rare occurrence of a large extradural extramedullary hematopoiesis in a patient with no known predisposing factor for hemopoiesis at the time of presentation.

  2. A rare cause of cytopenia in a patient with systemic lupus erythematosus: Autoimmune myelofibrosis

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    Cansu, Döndü Üsküdar; Teke, Hava Üsküdar; Korkmaz, Cengiz

    2017-01-01

    Hematological abnormalities are very common in the course of systemic lupus erythematosus (SLE). Myelofibrosis is a bone marrow disorder in which there is excessive fibrous tissue formation in the bone marrow. Various benign and malignant disorders can cause or be associated with a diffuse increase in the bone marrow reticular tissue. Some diseases such as infections, neoplasms, and autoimmune diseases may also induce bone marrow fibrosis (secondary myelofibrosis). Cytopenia from autoimmune myelofibrosis (AIMF) in SLE is a rare condition. Here we present a case of AIMF associated with SLE and aim to emphasize on the other cause of cytopenia in SLE. PMID:28293461

  3. Primary Myelofibrosis

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    ... the blood cells. Symptoms of primary myelofibrosis include pain below the ribs on the left side and feeling very tired. ... if you have any of the following: Feeling pain or fullness below the ribs on the left side. Feeling full sooner than ...

  4. Primary myelofibrosis L.

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    L. M. Meshcheryakova

    2014-07-01

    Full Text Available Literature data of idiopathic myelofibrosis are presented: classification, diagnostic criteria, morphological and molecular features. Particular attention is given to therapy of various clinical forms of primary myelofibrosis.

  5. Genetics Home Reference: primary myelofibrosis

    Science.gov (United States)

    ... Other Diagnosis and Management Resources (3 links) Merck Manual Professional Version: Primary Myelofibrosis Myeloproliferative Neoplasm (MPN) Research Foundation: Primary Myelofibrosis (PMF) National Organization for Rare Disorders (NORD) Physician Guide General Information ...

  6. DNA methylation profiling of sorted cells from myelofibrosis patients reveals aberrant epigenetic regulation of immune pathways and identifies early MPN driver genes

    DEFF Research Database (Denmark)

    Nielsen, H. M.; Andersen, C. L.; Kristensen, L. S.

    2015-01-01

    , PV) toadvancedMF. Multiple studies report frequent mutations in epigenetic regulators. However, the association to epigenetic changes and the role of epigenetic aberrations in different cell populations is still unknown. Aims: We therefore performed DNA methylation profiling of sorted cells from MF...... and PV patients. Results: The number of differentially methylated CpG sites between MF cells and the respective counterparts from healthy donors differed extensively among the three cell populations analyzed. In MF CD34+ cells 1628 CpG sites were differentially methylated compared to normal CD34+ cells......Background: Primary myelofibrosis (PMF) belongs to the heterogeneous group of chronic myeloproliferative neoplasms (MPN) together with essential thrombocytosis (ET) and polycythemia vera (PV). It has been suggested that these neoplasms represent a biological continuum from early cancer stage (ET...

  7. Hypercalcemia in idiopathic myelofibrosis

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    Voss, A; Schmidt, K; Hasselbalch, H;

    1992-01-01

    A case of idiopathic myelofibrosis (IMF) presenting with hypercalcemia and hypercalcitriolemia is reported. It is proposed that ectopic production of the active vitamin D metabolite related to ongoing clonal expansion in the bone marrow accounts for the hypercalcemic state. Consistently low level...... of circulating type I procollagen propeptide (PICP) and lack of progression of the bone marrow fibrosis during almost 6 months of follow-up point to an in vivo inhibition of type I collagen synthesis by 1,25-dihydroxyvitamin D3....

  8. Recent developments in myelofibrosis

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    Mesa RA

    2012-07-01

    Full Text Available Raoul Tibes, James M Bogenberger, Ruben A MesaDivision of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USAAbstract: The myeloproliferative neoplasm of myelofibrosis (MF is clinically constituted by individuals both with primary MF, as well as those that evolved from an antecedent polycythemia vera or essential thrombocythemia. Individuals presenting with MF have a heterogeneous phenotype which can involve significant constitutional symptoms (night sweats, fevers, weight loss, fatigue, variable but frequently problematic splenomegaly, and multifactorial cytopenias. These individuals clearly have decreased survival. Refinement of MF prognostic scores can distinguish from survival as poor as 16 months, to a median survival of 185 months. Sadly, although curative, allogeneic stem cell transplant still has sobering success rates for individuals of the standard ages for MF. Recent reports suggest less than half of patients will be alive at 3 years after allotransplant above the age of 60 years. The most important recent advancement in MF therapy has been the development of Janus kinase 2 (JAK2 inhibitors led by ruxolitinib, now Food and Drug Administration approved in the United States, and several other JAK2 inhibitors (in testing including SAR302503, CYT387, and SB1518. In randomized, placebo-controlled studies, ruxolitinib was demonstrated to be superior for the improvement of splenomegaly and symptoms. These benefits are mirrored across other JAK2 inhibitors. Improving anemia remains an unmet need in MF and is currently being evaluated by clinical trials utilizing the JAK2 inhibitor CYT387, as well as pomalidomide. Additional areas of interest for MF therapy include the inhibition of histone/lysine deacetylases, hedgehog pathway inhibition, as well as combination strategies with JAK2 inhibitors.Keywords: myeloproliferative neoplasm, myelofibrosis, JAK2 inhibitors

  9. The impact of donor myelofibrosis on outcome of renal transplantation

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    Tahawar Rana

    2013-01-01

    Full Text Available In donors known to have medical conditions associated with kidney damage, caution is exercised when accepting donor kidneys. Myelofibrosis can affect kidney function in a variety of ways, but is not generally considered a contraindication to donation. We present the case of a 27-year-old woman with known myelofibrosis who died from an upper gastrointestinal bleed. After cardiac death, both the kidneys were donated. The first recipient was a 34-year-old lady with focal segmental glomerular sclerosis in her single pelvic kidney. There was delayed graft function and the kidney continued to function poorly due to a significant donor vascular disease. The second recipient was a 27-year-old man with posterior urethral valves. Similar donor vascular disease caused this transplant to fail. The kidney damage did not fit any pattern reported in myelofibrosis, but may represent part of a spectrum of damage seen with this disease. This case highlights the need for caution when accepting kidneys from donors with chronic medical conditions even when young, and may be of use to transplant teams when considering accepting future donations from patients with myelofibrosis.

  10. Evidence that prefibrotic myelofibrosis is aligned along a clinical and biological continuum featuring primary myelofibrosis.

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    Giovanni Barosi

    Full Text Available PURPOSE: In the WHO diagnostic classification, prefibrotic myelofibrosis (pre-MF is included in the category of primary myelofibrosis (PMF. However, strong evidence for this position is lacking. PATIENTS AND METHODS: We investigated whether pre-MF may be aligned along a clinical and biological continuum in 683 consecutive patients who received a WHO diagnosis of PMF. RESULTS: As compared with PMF-fibrotic type, pre-MF (132 cases showed female dominance, younger age, higher hemoglobin, higher platelet count, lower white blood cell count, smaller spleen index and higher incidence of splanchnic vein thrombosis. Female to male ratio and hemoglobin steadily decreased, while age increased from pre-MF to PMF- fibrotic type with early and to advanced bone marrow (BM fibrosis. Likely, circulating CD34+ cells, LDH levels, and frequency of chromosomal abnormalities increased, while CXCR4 expression on CD34+ cells and serum cholesterol decreased along the continuum of BM fibrosis. Median survival of the entire cohort of PMF cases was 21 years. Ninety-eight, eighty-one and fifty-six percent of patients with pre-MF, PMF-fibrotic type with early and with advanced BM fibrosis, respectively, were alive at 10 years from diagnosis. CONCLUSION: Pre-MF is a presentation mode of PMF with a very indolent phenotype. The major consequences of this contention is a new clinical vision of PMF, and the need to improve prognosis prediction of the disease.

  11. Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis.

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    Hasselbalch, Hans Carl; Bjerrum, Ole Weiss; Jensen, Bjarne Anker; Clausen, Nielsaage Tøffner; Hansen, Per Boye; Birgens, Henrik; Therkildsen, Marianne Hamilton; Ralfkiaer, Elisabeth

    2003-12-01

    and thrombocytosis are seen in most patients with myelofibrosis during treatment with imatinib. Combination therapy with HU or IFN seems safe and well tolerated and followed by a decrease in disease activity. A subgroup of patients in an early disease phase might benefit from imatinib therapy alone. Copyright 2003 Wiley-Liss, Inc.

  12. Thalidomide and lenalidomide in primary myelofibrosis.

    NARCIS (Netherlands)

    Holle, N.; Witte, T.J.M. de; Mandigers, C.M.P.W.; Schaap, N.P.M.; Raymakers, R.A.P.

    2010-01-01

    Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic options once cytopenia has developed are limited to supportive care, such as erythrocyte tran

  13. Myelofibrosis

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    ... to your tissues) White blood cells (which fight infection) Platelets (which help your blood clot) When the bone marrow is scarred, it cannot make enough blood cells. Anemia , ... higher risk for infections may occur. As a result, the liver and ...

  14. Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET)

    DEFF Research Database (Denmark)

    Barosi, Giovanni; Bordessoule, Dominique; Briere, Jean;

    2005-01-01

    The European Myelofibrosis Network (EUMNET), a European research network on myelofibrosis with myeloid metaplasia (MMM), has developed a definition of response for the disease by using clinicohematologic, histologic, and cytogenetic criteria. A core set of 5 clinicohematologic criteria was selected...

  15. Primary myelofibrosis: own experience and news from diagnostic and treatment

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    K. M. Abdulkadyrov

    2015-01-01

    Full Text Available The newest advances in primary myelofibrosis (PMF pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors trials results are discussed.

  16. Primary myelofibrosis: own experience and news from diagnostic and treatment

    Directory of Open Access Journals (Sweden)

    K. M. Abdulkadyrov

    2015-06-01

    Full Text Available The newest advances in primary myelofibrosis (PMF pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors trials results are discussed.

  17. Does Early Adolescent Sex Cause Depressive Symptoms?

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    Sabia, Joseph J.

    2006-01-01

    A recent study by the Heritage Foundation (Rector, Johnson, & Noyes, 2003) found evidence of a positive relationship between early sexual intercourse and depressive symptoms. This finding has been used to bolster support for funding abstinence only sex education. However, promoting abstinence will only yield mental health benefits if there is…

  18. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

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    Zahr, Abdallah Abou; Salama, Mohamed E.; Carreau, Nicole; Tremblay, Douglas; Verstovsek, Srdan; Mesa, Ruben; Hoffman, Ronald; Mascarenhas, John

    2016-01-01

    Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID:27252511

  19. Tetraspanin CD9 participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis

    DEFF Research Database (Denmark)

    Desterke, Christophe; Martinaud, Christophe; Guerton, Bernadette

    2015-01-01

    Primary myelofibrosis is characterized by clonal myeloproliferation, dysmegakaryopoiesis, extramedullary hematopoiesis associated with myelofibrosis and altered stroma in the bone marrow and spleen. The expression of CD9, a tetraspanin known to participate in megakaryopoiesis, platelet formation,...

  20. Efficacy of ALK5 inhibition in myelofibrosis

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    Zhao, Wanke; Ho, Wanting Tina; Han, Ying; Murdun, Cem; Mailloux, Adam W.; Zhang, Ling; Wang, Xuefeng; Budhathoki, Anjali; Pradhan, Kith; Rapaport, Franck; Wang, Huaquan; Shao, Zonghong; Ren, Xiubao; Steidl, Ulrich; Levine, Ross L.; Zhao, Zhizhuang Joe; Verma, Amit; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPLW515L megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF.

  1. Successful Control of Acute Myelofibrosis with Lenalidomide

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    G. Vassilopoulos

    2010-01-01

    Full Text Available Acute panmyelosis with myelofibrosis (APMF is a rare, fatal hematological neoplasm that is characterized by the acute onset of cytopenias and fibrosis in the bone marrow in the absence of splenomegaly or fibrosis-related morphological changes in the RBCs. We present the case of a 59-year-old female who presented with a two-month history of anemia, leucopenia and a normal platelet count. The marrow was heavily fibrotic, and no aspirate material could be obtained; the biopsy showed extensive infiltration with small to medium size megakaryocytes, dysplastic changes in the erythroid compartment, and left shift in the myeloid cells. The patient was treated for four months with anabolic steroids (Danazol, growth factors and received regular blood transfusions. At 4 months after diagnosis, the patient was started on Lenalidomide, 10 mg/day for a 21-d-course along with growth factor support. At 6 months after treatment, the patient was transfusion-independent, had normalized blood counts, and, at 32 months on continuous lenalidomide treatment, her needs for growth factor support have been minimized. Repeat bone marrow biopsies showed a patchy distribution of fibrosis with areas of normal cellularity and morphology. To our knowledge, this is the first case for a medication that could reverse the fatal outcome of APMF.

  2. Coexistence of primary myelofibrosis and chronic lymphocytic leukemia

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    Burgstaller S

    2014-10-01

    Full Text Available Sonja Burgstaller, Josef Thaler Klinikum Wels-Grieskirchen, Abteilung für Innere Medizin IV, Wels, AustriaAbstract: Coexistence of two hematologic malignancies in one patient is generally a rare phenomenon. The topic of this article is the coincidence of primary myelofibrosis and chronic lymphocytic leukemia, which has been reported up to now in only 16 patients. In summary, simultaneous detection of both diseases was notable in half of the patients at presentation. In the case of a subsequent diagnosis of both disorders, primary myelofibrosis preceded the lymphoproliferative disease in the majority of patients. The clinical course seems to be more benign than for each disorder itself. A substantial proportion of patients did not require any treatment at all. Knowledge about the pathogenetic mechanisms, treatment approaches, and prognosis of these patients is limited.Keywords: primary myelofibrosis, chronic lymphocytic leukemia, coexistent

  3. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

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    Bueso-Ramos, Carlos E.; Newberry, Kate J.; Knez, Liza; Post, Sean M.; Ahn, Jihae; Levine, Ross L.; Kantarjian, Hagop M.

    2016-01-01

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  4. Recent advances in understanding myelofibrosis and essential thrombocythemia [version 1; referees: 2 approved

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    William Vainchenker

    2016-04-01

    Full Text Available The classic BCR-ABL-negative myeloproliferative neoplasms (MPNs, a form of chronic malignant hemopathies, have been classified into polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF. ET and PMF are two similar disorders in their pathogenesis, which is marked by a key role of the megakaryocyte (MK lineage. Whereas ET is characterized by MK proliferation, PMF is also associated with aberrant MK differentiation (myelodysplasia, leading to the release of cytokines in the marrow environment, which causes the development of myelofibrosis. Thus, PMF is associated with both myeloproliferation and different levels of myelodysplastic features. MPNs are mostly driven by mutated genes called MPN drivers, which abnormally activate the cytokine receptor/JAK2 pathway and their downstream effectors. The recent discovery of CALR mutations has closed a gap in our knowledge and has shown that this mutated endoplasmic reticulum chaperone activates the thrombopoietin receptor MPL and JAK2. These genetic studies have shown that there are two main types of MPNs: JAK2V617F-MPNs, including ET, PV, and PMF, and the MPL-/CALR-MPNs, which include only ET and PMF. These MPN driver mutations are associated with additional mutations in genes involved in epigenetics, splicing, and signaling, which can precede or follow the acquisition of MPN driver mutations. They are involved in clonal expansion or phenotypic changes or both, leading to myelofibrosis or leukemic transformation or both. Only a few patients with ET exhibit mutations in non-MPN drivers, whereas the great majority of patients with PMF harbor one or several mutations in these genes. However, the entire pathogenesis of ET and PMF may also depend on other factors, such as the patient’s constitutional genetics, the bone marrow microenvironment, the inflammatory response, and age. Recent advances allowed a better stratification of these diseases and new therapeutic approaches with

  5. Ruxolitinib is manageable in patients with myelofibrosis and severe thrombocytopenia

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Holmström, Morten Orebo; Hasselbalch, Hans Carl

    2016-01-01

    We report 12 Danish myelofibrosis patients who have been treated successfully with ruxolitinib despite having low platelet counts (< 50 × 10(9)/L) during their treatment-course. The majority of the patients experienced marked clinical improvement. Serious side effects were only recorded in a sing...

  6. Transcriptional profiling of whole blood identifies a unique 5-gene signature for myelofibrosis and imminent myelofibrosis transformation

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    Hasselbalch, Hans Carl; Skov, Vibe; Stauffer Larsen, Thomas

    2014-01-01

    selectively and highly deregulated in myelofibrosis patients. Gene expression microarray studies have been performed on whole blood from 69 patients with myeloproliferative neoplasms. Amongst the top-20 of the most upregulated genes in PMF compared to controls, we identified 5 genes (DEFA4, ELA2, OLFM4, CTSG...

  7. Management of myelofibrosis during pregnancy: A case report

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    Živković Radmila

    2015-01-01

    Full Text Available Introduction. Primary myelofibrosis (PMF is a clonal myeloproliferative neoplasm that occurs most commonly in the decade six of life and it is very rare in the young persons. Case report. We reported a 28-year-old female patient with primary myelofibrosis who had a normal pregnancy and delivery in the week 40 of pregnancy without any complications. Two years before the diagnosis of PMF she had normal pregnancy. The patient was treated with interferon-alpha and low dose aspirin during the whole pregnancy and with low-molecular-weight heparin a week before delivery and 6 weeks after. The patient had no complications during pregnancy. She delivered in term with healthy, normal baby weight. Conclusion. Decision about treatment strategy of pregnancy associated hematologic malignancies should be made for each patient individually.

  8. Pantoea species causing early onset neonatal sepsis: a case report.

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    Tiwari, Shreekant; Beriha, Siba Shankar

    2015-09-04

    Pantoea agglomerans is a plant pathogen which very rarely causes an opportunistic infection. Human beings are usually infected by thorn prick injuries or by contaminated parenteral fluids. Pantoea agglomerans has been reported as a cause of neonatal sepsis very rarely and to the best of our knowledge this is the first reported case from India. A 4-day-old Asian baby boy from the rural area of Odisha, India, was admitted to our neonatal intensive care unit when he presented with fever, tachypnea and chest retraction. Pantoea species were isolated from his blood culture. He was treated successfully with meropenem administered intravenously and other supportive measures. Early detection and proper management may cause a favorable outcome.

  9. Early pathogenesis in porcine proliferative enteropathy caused by Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Boutrup, Torsten Snogdal; Boesen, H. T.; Boye, Mette

    2010-01-01

    The intestinal bacterium Lawsonia intracellularis, the cause of proliferative enteropathy (PE) in pigs, is believed to infect mitotically active epithelial cells of the intestinal crypts and then multiply and spread in these cells as they divide. Further spread of infection is thought to occur...... by shedding of bacteria from infected crypts followed by infection of new crypts. The early stages of the pathogenesis of PE, from 0 to 48 hours post-infection (hpi), have not been studied in vivo. In the present study pigs were inoculated with L. intracellularis and killed from 12 hpi to 5 days post...... enterocytes. Furthermore, early invasion of the intestinal connective tissue was observed; with the presence of single bacteria in the lamina propria 12 hpi, and with a further spread of bacteria in the lamina propria observed at 5 dpi, suggesting an active role for the lamina propria in the course...

  10. Circulating YKL-40 in myelofibrosis a potential novel biomarker of disease activity and the inflammatory state

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    Bjørn, Mads Emil; Andersen, Christen Lykkegaard; Jensen, Morten Krogh;

    2014-01-01

    Chronic myeloproliferative neoplasms (MPN), encompassing essential thrombocythaemia (ET), polycythaemia vera (PV) and myelofibrosis (PMF), are featured by a chronic inflammatory state which is pronounced in myelofibrosis The value of YKL-40 as a biomarker of disease burden has been demonstrated i...

  11. Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

    DEFF Research Database (Denmark)

    Lisse, I; Hasselbalch, H; Junker, P

    1991-01-01

    Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...... and capillarization, with the development of continuous sheets of basement membrane material beneath endothelial cells....

  12. Primary autoimmune myelofibrosis: a report of three cases and review of the literature

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    Rakhee Kar

    2009-09-01

    Full Text Available Myelofibrosis in association with autoimmune disorders has been consistently recognized in sporadic case reports over a number of years. Autoimmune myelofibrosis has been described most commonly in association with systemic lupus erythematosus (SLE. In addition, myelofibrosis presenting as cytopenias and showing clinical response to immunosuppressant drugs, notably steroids, has been reported with a wide range of immune-mediated disorders, including Sjögren’s syndrome, polyarteritis nodosa, rheumatoid arthritis, ulcerative colitis, and primary biliary cirrhosis. Attempts have been made to define a syndrome of primary autoimmune myelofibrosis (PAIMF, as a distinct steroid-responsive clinicopathologic entity with excellent prognosis. Herein, we describe three cases of autoimmune myelofibrosis with a review of the literature.

  13. Tetraspanin CD9 participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis.

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    Desterke, Christophe; Martinaud, Christophe; Guerton, Bernadette; Pieri, Lisa; Bogani, Costanza; Clay, Denis; Torossian, Frederic; Lataillade, Jean-Jacques; Hasselbach, Hans C; Gisslinger, Heinz; Demory, Jean-Loup; Dupriez, Brigitte; Boucheix, Claude; Rubinstein, Eric; Amsellem, Sophie; Vannucchi, Alessandro M; Le Bousse-Kerdilès, Marie-Caroline

    2015-06-01

    Primary myelofibrosis is characterized by clonal myeloproliferation, dysmegakaryopoiesis, extramedullary hematopoiesis associated with myelofibrosis and altered stroma in the bone marrow and spleen. The expression of CD9, a tetraspanin known to participate in megakaryopoiesis, platelet formation, cell migration and interaction with stroma, is deregulated in patients with primary myelofibrosis and is correlated with stage of myelofibrosis. We investigated whether CD9 participates in the dysmegakaryopoiesis observed in patients and whether it is involved in the altered interplay between megakaryocytes and stromal cells. We found that CD9 expression was modulated during megakaryocyte differentiation in primary myelofibrosis and that cell surface CD9 engagement by antibody ligation improved the dysmegakaryopoiesis by restoring the balance of MAPK and PI3K signaling. When co-cultured on bone marrow mesenchymal stromal cells from patients, megakaryocytes from patients with primary myelofibrosis displayed modified behaviors in terms of adhesion, cell survival and proliferation as compared to megakaryocytes from healthy donors. These modifications were reversed after antibody ligation of cell surface CD9, suggesting the participation of CD9 in the abnormal interplay between primary myelofibrosis megakaryocytes and stroma. Furthermore, silencing of CD9 reduced CXCL12 and CXCR4 expression in primary myelofibrosis megakaryocytes as well as their CXCL12-dependent migration. Collectively, our results indicate that CD9 plays a role in the dysmegakaryopoiesis that occurs in primary myelofibrosis and affects interactions between megakaryocytes and bone marrow stromal cells. These results strengthen the "bad seed in bad soil" hypothesis that we have previously proposed, in which alterations of reciprocal interactions between hematopoietic and stromal cells participate in the pathogenesis of primary myelofibrosis. Copyright© Ferrata Storti Foundation.

  14. Early dioxin exposure causes toxic effects in adult zebrafish.

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    Baker, Tracie R; Peterson, Richard E; Heideman, Warren

    2013-09-01

    The acute effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure have been well documented in many vertebrate species. However, less is known about the consequences in adulthood from sublethal exposure during development. To address this, we exposed zebrafish to sublethal levels of TCDD (1h; 50 pg/ml), either in early embryogenesis (day 0) or during sexual determination (3 and 7 weeks), and assessed the effects later in adulthood. We found that exposure during embryogenesis produced few effects on the adults themselves but did affect the offspring of these fish: Malformations and increased mortality were observed in the subsequent generation. Zebrafish exposed during sexual development showed defects in the cranial and axial skeleton as adults. This was most clearly manifested as scoliosis caused by malformation of individual vertebrae. These fish also showed defects in reproduction, producing fewer eggs with lower fertilization success. Both males and females were affected, with males contributing to the decrease in egg release from the females and exposed females contributing to fertilization failure. TCDD exposure at 3 and 7 weeks produced feminization of the population. Surprisingly, part of this was due to the appearance of fish with clearly female bodies, yet carrying testes in place of ovaries. Our results show that exposures that produce little if any impact during development can cause severe consequences during adulthood and present a model for studying this process.

  15. Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

    Science.gov (United States)

    Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-10-06

    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Causes of early childhood deaths in urban Dhaka, Bangladesh.

    Directory of Open Access Journals (Sweden)

    Amal K Halder

    Full Text Available Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD+/-7.3. Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006-2007. The leading cause of under-five death was respiratory infections (22%. The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year were similar (36 versus 32. The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years.

  17. Idiopathic myelofibrosis with generalized periostitis in a 4-year-old girl.

    Science.gov (United States)

    Walia, Mandeep; Mehta, Rajesh; Paul, Premila; Saluja, Sumita; Kapoor, Sujala; Sharma, Monika

    2005-05-01

    Idiopathic myelofibrosis, a chronic myeloproliferative disorder of unknown origin, is characterized by splenomegaly, extramedullary hematopoiesis, leukoerythroblastosis, teardrop erythrocytes, and myelofibrosis. It is a rare disorder in childhood. The authors describe a 4-year-old girl with features consistent with idiopathic myelofibrosis, who also had generalized solid laminated periosteal reaction involving all long bones. The presence of thrombocytopenia at the onset and lack of leukocytosis were in contrast to the reported features seen in children. Recent case reports describe a relatively indolent course in children. Spontaneous remissions have also been described in pediatric cases. The fulminant course of this patient without any features of malignant transformation was noteworthy in this regard.

  18. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes

    Directory of Open Access Journals (Sweden)

    Sochacki AL

    2016-04-01

    Full Text Available Andrew L Sochacki,1 Melissa A Fischer,1 Michael R Savona1,2 1Department of Internal Medicine, Vanderbilt University Medical Center, 2Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Abstract: The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph- myeloproliferative neoplasms. Unlike BCR–ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF, post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS/myeloproliferative neoplasm (MPN syndromes. JAK–STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK–STAT, hedgehog, PI3K–Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. Keywords: MDS/MPN neoplasms, emerging therapy

  19. Myelofibrosis-Related Arthritis Successfully Treated with Hydroxyurea

    Directory of Open Access Journals (Sweden)

    Xavier Guillot

    2014-01-01

    Full Text Available A 62-year-old woman suffering from one-year lasting, nonerosive peripheral arthritides with general health impairment and high acute-phase reactant levels was admitted to rheumatology department. The patient had suffered from chronic polyarthralgia and a thrombocytosis had been discovered 9 years before, with a recent increase in platelet count. All immunological blood tests were negative. Corticosteroid and methotrexate treatments improved pain, swollen joint count, and systemic inflammation. However, joints remained stiff and painful with two swollen wrists and persistent thrombocytosis. An iliac bone marrow biopsy was performed, showing primary myelofibrosis. Hydroxyurea treatment (500 mg per day allowed to achieve complete and prolonged clinical and biological remission. After 6 months, a new disease flare occurred. The patient reached remission again after hydroxyurea dose increased to 1500 mg per day. This supports the hypothesis of idiopathic myelofibrosis-associated seronegative polyarthritis. This is the first reported case in which haemopathy-targeted treatment using hydroxyurea induced arthritis remission.

  20. Early Bolting in Short Days: An Arabidopsis Mutation That Causes Early Flowering and Partially Suppresses the Floral Phenotype of leafy

    National Research Council Canada - National Science Library

    Concepción Gómez-Mena; Manuel Piñeiro; José M. Franco-Zorrilla; Julio Salinas; George Coupland; José M. Martínez-Zapater

    2001-01-01

    .... Some of these signals promote the onset of flowering, whereas others repress it. We describe here the isolation and characterization of two allelic mutations that cause early flowering and define a new locus, EARLY BOLTING IN SHORT DAYS (EBS...

  1. Hypocellular myelodysplastic syndrome with myelofibrosis in acute myeloid leukemia transformation: A case report.

    Science.gov (United States)

    Song, Kui; Xu, Xiaojun; Li, Min

    2015-07-01

    Primary myelodysplastic syndrome (MDS) with myelofibrosis is a rare hematological disorder that should be classified as a distinct subgroup of MDS. Treatment of MDS with myelofibrosis remains problematic and the prognosis is poor in these patients, particularly following transformation into acute myeloid leukemia (AML). The current study presents the case of a 28-year-old male diagnosed with MDS associated with myelofibrosis, together with hypocellular bone marrow features. Following induction chemotherapy consisting of mitoxantrone and cytarabine, the patient achieved complete remission, but developed severe myelofibrosis. The patient relapsed and the disease transformed into AML 12 months later. However, the extent of the myelofibrosis was markedly alleviated upon administration of a FLAG regimen that consisted of fludarabine, cytarabine and granulocyte colony-stimulating factor during the AML transformation. After one course of the FLAG regimen, the patient achieved a second complete remission. As there was no suitable donor for hematopoietic stem cell transplantation (HSCT), the patient relapsed and succumbed shortly after. In conclusion, MDS with fibrosis is an aggressive disease, but the degree of myelofibrosis may not be associated with the progression of hypocellular MDS, and allogeneic HSCT remains a potentially curative option for affected patients.

  2. Profile of pomalidomide and its potential in the treatment of myelofibrosis

    Directory of Open Access Journals (Sweden)

    Gowin KL

    2015-04-01

    Full Text Available Krisstina L Gowin, Ruben A Mesa Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA Abstract: Myelofibrosis, a Philadelphia-negative myeloproliferative neoplasm, is in a new treatment era after the discovery of the JAK2V617F mutation in 2005. JAK inhibitors boast improvements in disease-related symptoms, splenomegaly, and overall survival; however, treatment of myelofibrosis remains a challenge, given the lack of improvement in cytopenias with these agents. Second-generation immunomodulatory agents, such as pomalidomide, have shown efficacy in myelofibrosis-associated anemia within multiple clinical trials. Five major pomalidomide clinical trials have been completed to date, and demonstrate tolerability and efficacy with low-dose pomalidomide (0.5 mg/day in the treatment of myelofibrosis, and no clinical benefit of elevated dosing regimens (≥2.5 mg/day. Anemia responses ranged from 17% to 36% as per the International Working Group for Myelofibrosis Research and Treatment consensus guidelines, while improvements in splenomegaly were rare, and observed in <1% of most clinical trials. In comparison with earlier immunomodulatory agents, pomalidomide was associated with an improved toxicity profile, with substantially lower rates of myelosuppression and neuropathy. Given the low overall response rate to pomalidomide as a single agent, combination strategies are of particular interest for future studies. Pomalidomide is currently being tested in combination with ruxolitinib, and other novel combinations are likely on the horizon. Keywords: myelofibrosis, pomalidomide, immunomodulatory, myeloproliferative neoplasm

  3. Causes of early Holocene desertification in arid central Asia

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Liya [Lanzhou University, Key Laboratory of Western China' s Environmental System, Lanzhou, Gansu (China); University of Kiel, Institute of Geosciences, Kiel (Germany); Chen, Fahu [Lanzhou University, Key Laboratory of Western China' s Environmental System, Lanzhou, Gansu (China); Morrill, Carrie [University of Colorado, Cooperative Institute for Research in Environmental Sciences, Boulder, CO (United States); NOAA' s National Climatic Data Center, Paleoclimatology Branch, Boulder, CO (United States); Otto-Bliesner, Bette L.; Rosenbloom, Nan [National Center for Atmospheric Research, Climate and Global Dynamics Division, Boulder, CO (United States)

    2012-04-15

    Paleoclimate records of effective moisture (precipitation minus evaporation, or P-E) show a dry (low effective moisture) period in mid-latitude arid/semi-arid central Asia during the early Holocene (11,000-8,000 years ago) relative to the middle and late Holocene, in contrast to evidence for greater-than-present precipitation at the same time in the south and east Asian monsoonal areas. To investigate the spatial differences in climate response over mid-latitude central Asia and monsoonal Asia we conducted a series of simulations with the Community Climate System Model version 3 coupled climate model for the early, middle and late Holocene. The simulations test the climatic impact of all important forcings for the early Holocene, including changes in orbital parameters, the presence of the remnant Laurentide ice sheet and deglacial freshening of the North Atlantic. Model results clearly show the early Holocene patterns indicated by proxy records, including both the decreased effective moisture in arid central Asia, which occurs in the model primarily during the winter months, and the increase in summer monsoon precipitation in south and east Asia. The model results suggest that dry conditions in the early Holocene in central Asia are closely related to decreased water vapor advection due to reduced westerly wind speed and less evaporation upstream from the Mediterranean, Black, and Caspian Seas in boreal winter. As an extra forcing to the early Holocene climate system, the Laurentide ice sheet and meltwater fluxes have a substantial cooling effect over high latitudes, especially just over and downstream of the ice sheets, but contribute only to a small degree to the early Holocene aridity in central Asia. Instead, most of the effective moisture signal can be explained by orbital forcing decreasing the early Holocene latitudinal temperature gradient and wintertime surface temperature. We find little evidence for regional subsidence related to a stronger summer Asian

  4. Ruxolitinib for the treatment of myelofibrosis: its clinical potential

    Directory of Open Access Journals (Sweden)

    Ostojic A

    2012-03-01

    Full Text Available Alen Ostojic1, Radovan Vrhovac1, Srdan Verstovsek21Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, Zagreb, Croatia; 2Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USAAbstract: Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF, a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with MF, ruxolitinib recipients exhibited durable reductions in spleen size, reductions in circulating pro-inflammatory cytokines, improvements in physical activity, weight gain, and alleviation of symptoms (including constitutional symptoms in patients with and without JAK2 mutation. These findings were confirmed by two phase III clinical MF studies, in which a greater proportion of ruxolitinib recipients achieved a spleen volume reduction of ≥35% from baseline at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001 and with best available therapy in the other (31.9% versus 0%; P < 0.0001. Alleviation of MF symptoms and improvements in quality of life were also significantly greater in ruxolitinib recipients. Overall survival of patients treated with ruxolitinib was significantly longer than of those receiving the placebo. Owing to risks of potentially serious adverse effects, eg, myelosuppression, ruxolitinib should be used under close physician supervision. Longer follow-up of the phase III MF studies is needed to reach firm conclusions regarding ruxolitinib’s capacity to modify the natural disease course.Keywords: myelofibrosis, JAK2 inhibitor, ruxolitinib

  5. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia

    Directory of Open Access Journals (Sweden)

    Leonardo Caires dos Santos

    2011-12-01

    Full Text Available BACKGROUND: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. OBJECTIVE: The aim of this study was to detect the following mutations: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. METHODS: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. RESULTS: Chromosomal abnormalities were observed only in polycythemia vera (11.8% and primary myelofibrosis cases (17.6%, without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%, primary myelofibrosis (42.8% and essential thrombocythemia (47%. Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively. JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022. JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia

  6. Early causes of child obesity and implications for prevention

    OpenAIRE

    Cole, T J

    2007-01-01

    Child obesity is becoming a serious public health concern, and major research effort is being devoted both to understand its aetiology and to improve the effectiveness of prevention strategies. Early growth patterns, both prenatally and postnatally, are emerging as important markers of later obesity risk, with rapid neonatal weight gain a clear risk factor for later obesity and metabolic syndrome. Thus, in two distinct senses child obesity is a growing problem. The paper summarises current ev...

  7. Early Prediction of Transient Voltage Sags caused by Rotor Swings

    DEFF Research Database (Denmark)

    Weckesser, Johannes Tilman Gabriel; Jóhannsson, Hjörtur; Van Cutsem, Thierry

    2014-01-01

    The paper investigates various methods to predict voltage sags at load buses caused by large generator rotor swings and following a transient disturbance. Three different prediction methods are proposed, which all use real-time measurements from PMUs. One of the methods uses a slightly extended v...

  8. Early death in active professional athletes: Trends and causes.

    Science.gov (United States)

    Lemez, S; Wattie, N; Baker, J

    2016-05-01

    The objective of the study was to examine mortality trends and causes of death among professional athletes from the four major sports in North America who died during their playing careers. 205 deceased athletes who were registered as active when they died from the National Basketball Association (NBA), National Football League (NFL), National Hockey League (NHL), and Major League Baseball (MLB) were examined. Results were compared with the Canadian and U.S. general population. The leading causes of death in players reflected the leading causes of death in the Canadian and U.S. general population (i.e., car accidents). Descriptively, NFL and NBA players had a higher likelihood of dying in a car accident (OR 1.75, 95% CI: 0.91-3.36) compared with NHL and MLB players. In addition, NFL and NBA players had a significantly higher likelihood of dying from a cardiac-related illness (OR 4.44, 95% CI: 1.59-12.43). Mortality trends were disproportionate to team size. Overall, death in active athletes is low. Out of 53 400 athletes who have historically played in the four leagues, only 205 died while active (0.38%). Future examinations into the trends and causes of mortality in elite athlete populations will create a better understanding of health-related risks in elite sport. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

    Science.gov (United States)

    Hagemann, Jürgen Benjamin; Essig, Andreas; Herrmann, Manuel; Liebold, Andreas; Quader, Mohamed Abo

    2015-12-01

    Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment.

  10. Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis-induced portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Koichi Tokai; Hiroyuki Miyatani; Yukio Yoshida; Shigeki Yamada

    2012-01-01

    A 75-year old man had been diagnosed at 42 years of age as having polycythemia vera and had been monitored at another hospital.Progression of anemia had been recognized at about age 70,and the patient was thus referred to our center in 2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy findings.Hematemesis due to rupture of esophageal varices occurred in January and February of 2011.The bleeding was stopped by endoscopic variceal ligation.Furthermore,in March of the same year,hematemesis recurred and the patient was transported to our center.He was in irreversible hemorrhagic shock and died.The autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers,an observation consistent with myelofibrosis.The liver weighed 1856 g the spleen 1572 g,indicating marked hepatosplenomegaly.The liver and spleen both showed extramedullary hemopoiesis.Myelofibrosis is often complicated by portal hypertension and is occasionally associated with gastrointestinal hemorrhage due to esophageal varices.A patient diagnosed as having myelofibrosis needs to be screened for esophageal/gastric varices.Myelofibrosis has a poor prognosis.Therefore,it is necessary to carefully decide the therapeutic strategy in consideration of the patient's concomitant conditions,treatment invasiveness and quality of life.

  11. Early repolarization syndrome: A cause of sudden cardiac death

    Institute of Scientific and Technical Information of China (English)

    Abdi; Ali; Nida; Butt; Azeem; S; Sheikh

    2015-01-01

    Early repolarization syndrome(ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life- threatening arrhythmias and sudden cardiac death(SCD). Early repolarization characteristics associated with SCD include high-amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation(0.05 m V vs 0.1 m V) being the main determinants.ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life- threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.

  12. Multi-drug resistant gram negative bacilli causing early neonatal sepsis in India.

    Science.gov (United States)

    Viswanathan, Rajlakshmi; Singh, Arun Kumarendu; Basu, Sulagna; Chatterjee, Suparna; Sardar, Syamal; Isaacs, David

    2012-05-01

    To study the organisms causing early and late onset neonatal sepsis, with special reference to multi-drug resistant gram negative bacilli, at two neonatal units (one urban, one rural) in India. Prospective surveillance study. There were 159 episodes of sepsis (81 urban and 77 rural) affecting 158 babies. Gram negative bacilli caused 117 infections (68%) and predominated at both centres in both early and late sepsis. Klebsiella pneumoniae was the commonest organism, causing 61 infections (38.3%). In early sepsis (0-2 days), non-fermenting gram negative bacilli caused 42.1% of infections at the urban centre; there were no cases of early Group B Streptococcus sepsis. Late onset sepsis was mainly caused by gram negative bacilli at both centres. Multi-drug resistance of over 80% of early-onset gram negative organisms to ampicillin, third generation cephalosporins and gentamicin indicates that these multi-resistant organisms are almost certainly circulating widely in the community. The overall mortality from early sepsis was 27.3% (9 of 33) and from late sepsis was 26.2% (33 of 126). Gram negative bacilli caused all deaths from early sepsis and 87.5% of deaths from late sepsis. This study shows that multi-drug resistant gram negative bacilli are a major cause of early and late neonatal sepsis in India and are almost certainly widespread in the community.

  13. Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis.

    Science.gov (United States)

    Shinar, Yael; Tohami, Tali; Livneh, Avi; Schiby, Ginette; Hirshberg, Abraham; Nagar, Meital; Goldstein, Itamar; Cohen, Rinat; Kukuy, Olga; Shubman, Ora; Sharabi, Yehonatan; Gonzalez-Roca, Eva; Arostegui, Juan I; Rechavi, Gideon; Amariglio, Ninnette; Salomon, Ophira

    2015-06-30

    A study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1-2 day long self-limited periodic episodes of high fever that became more frequent as the hematologic disease progressed. After ruling out other causes for recurrent fever, analysis of the pyrin encoding Mediterranean fever gene (MEFV) was carried out by Sanger sequencing in peripheral blood DNA samples obtained 4 years apart, in buccal cells, laser dissected kidney tubular cells, and FACS-sorted CD3-positive or depleted mononucleated blood cells. Hematopoeitc cells results were validated by targeted deep sequencing. A Sanger sequence based screen for pathogenic variants of the autoinflammatory genes NLRP3, TNFRSF1A and MVK was also performed. A rare, c.1955G>A, p.Arg652His MEFV gene variant was identified at negligible levels in an early peripheral blood DNA sample, but affected 46 % of the MEFV alleles and was restricted to JAK2-positive, polymorphonuclear and CD3-depleted mononunuclear DNA samples obtained 4 years later, when the patient experienced fever bouts. The patient was also heterozygous for the germ line, non-pathogenic NLRP3 gene variant, p.Q705K. Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided. This is the first report of non-transmitted, acquired FMF, associated with a JAK2 driven clonal expansion of a somatic MEFV exon 10 mutation. The non-pathogenic germ line NLRP3 p.Q705K mutation possibly played a modifier role on the disease phenotype.

  14. Splenic irradiation in myelofibrosis. Clinical findings and ferrokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, C.; Charbord, P.; Tibi, M.; Tubiana, M.

    1977-01-01

    Nine patients were submitted to splenic or, in two cases, hepatosplenic irradiation; these patients presented a primary myelofibrosis or a spent polycythemia vera characterized by splenomegaly, anemia, and occasionally leucocytosis and thrombocytopenia. The hematological condition returned to normal in 2 patients. This improvement lasted 4 years after a first series of irradiation. The recurrence of splenomegaly and anemia indicated a second series of irradiation, the results of which were as good as those of the first series. Ineffective medullary and splenic erythropoiesis without preeminent aplasia appeared to be correlated with a beneficial effect of splenic irradiation. Absence of hepatomegaly and marked leucocytosis were less important prognostic factors. The modee of action of radiotherapy and the way in which it differs from splenectomy are discussed. The irradiation delivered moderate doses (450 rad in 18 sessions of 25 rad). Hepatic irradiation did not appear to be essential even in cases of intense hepatic myeloid metaplasia: in 2 patients liver erythropoiesis regressed when the spleen alone was irradiated.

  15. Myelofibrosis: an update on current pharmacotherapy and future directions.

    Science.gov (United States)

    Cervantes, Francisco; Martinez-Trillos, Alejandra

    2013-05-01

    Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by symptoms mainly derived from anemia and splenomegaly and constitutional symptoms and associated with a median survival around 6 years. Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapy of MF but is applicable to a minority of patients. Discovery of the JAK2 mutation has provided the basis for the introduction of a new class of drugs, the JAK inhibitors, in the treatment of MF. A literature review on the therapy of MF has been performed through a PubMed search, with special attention being paid to the available data on transplantation, the JAK inhibitors, and other new drugs. Conventional therapy of MF is usually adjusted to the predominant clinical symptoms in each patient, and its impact on survival is limited. Reduced-intensity conditioning regimens have increased the number of patients eligible for allo-SCT, but this procedure is still associated with substantial morbidity and mortality. The JAK inhibitors, such as ruxolitinib, can achieve profound symptomatic relief of the splenomegaly and the constitutional symptoms. However, they often accentuate the anemia and do not reduce the JAK2 allele burden, therefore lacking the potential to modify the natural history of MF.

  16. Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia

    Energy Technology Data Exchange (ETDEWEB)

    Tefferi, A.; Jimenez, T.; Gray, L.A.; Mesa, R.A. [Division of Hematology and Internal Medicine, Rochester, MN (United States); Chen, M.G. [Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, MN (United States)

    2001-07-01

    Objective: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). Methods: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50-1000) administered at a median of six fractions. Four patients received two to six courses. Results. Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1-23) and 4 were alive at 3, 20, 33, and 57 months after RT. Conclusions: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief. (au)

  17. Practical management of patients with myelofibrosis receiving ruxolitinib.

    Science.gov (United States)

    Harrison, Claire; Mesa, Ruben; Ross, David; Mead, Adam; Keohane, Clodagh; Gotlib, Jason; Verstovsek, Srdan

    2013-10-01

    Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients also experience debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi, Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA for the treatment of intermediate- or high-risk MF, and more recently in Europe and Canada for the treatment of MF-related splenomegaly or symptoms. These approvals were based on data from two randomized Phase III studies: COMFORT-I randomized against placebo, and COMFORT-II randomized against best available therapy. In these studies, ruxolitinib rapidly improved multiple disease manifestations of MF, reducing splenomegaly and improving quality of life of patients and potentially prolonging survival. However, as with other chemotherapies, ruxolitinib therapy is associated with some adverse events, such as anemia and thrombocytopenia. The aims of this article are to provide a brief overview of ruxolitinib therapy, to discuss some common adverse events associated with ruxolitinib therapy and to provide clinical management recommendations to maximize patients' benefit from ruxolitinib.

  18. Interleukin-10 inhibits autonomous myelopoiesis in patients with myelofibrosis.

    Science.gov (United States)

    Geissler, Klaus; Jäger, Eva; Öhler, Leopold; Gisslinger, Heinz; Jäger, Ulrich; Lechner, Klaus

    2015-09-01

    The spontaneous formation of colony-forming units granulocyte/macrophage (CFU-GM) in semisolid cultures has been shown to be due to the endogenous release of cytokines and/or to the hypersensitivity of cells against growth factors. We have reported that increased autonomous CFU-GM growth is an in vitro characteristic of myelofibrosis (MF) which may reflect aberrant hematopoiesis in vivo. Because of its cytokine synthesis-inhibiting action, we speculated that interleukin-10 (IL-10) may inhibit pathological overproduction of myeloid cells in MF by suppression of autonomous myelopoiesis. In this study, IL-10 significantly inhibited autonomous CFU-GM formation in vitro from peripheral blood mononuclear cells (PB MNC) in 10 of 11 patients with MF tested. In all patients, there was a mean inhibition of 69% ranging from 35% to 100%. Suppression of autonomous CFU-GM formation by IL-10 was dose dependent and reversible by the addition of anti-IL-10 antibodies. Our results indicate that IL-10 is a potentially useful molecule to affect aberrant myelopoiesis in patients with MF.

  19. Emerging treatment options for myelofibrosis: focus on pacritinib

    Directory of Open Access Journals (Sweden)

    Chow V

    2016-05-01

    Full Text Available Vivian Chow,1 Ashley Weissman,2 Casey Lee O’Connell,3 Azim Mehrvar,4 Mojtaba Akhtari3 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, 3Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; 4Mahak Children’s Cancer Treatment and Research Center, Tehran, Iran Abstract: Myelofibrosis (MF is a myeloid malignancy associated with a heavy symptomatic burden that decreases quality of life and presents a risk for leukemic transformation. While there are limited curative treatments, the recent discovery of the Janus kinase/signal transducer and activator of transcription (JAK/STAT pathway dysregulation has led to many clinical investigations for new treatment approaches. This review provides practical knowledge on the disease state, an overview of treatment options, and specifically focuses on the efficacy and safety of pacritinib in the management of MF. Pacritinib is a novel selective inhibitor of JAK2 and FMS-related tyrosine kinase 3 (FLT3 currently in Phase III trials for the treatment of MF. Thus far, studies have demonstrated clinical efficacy in reducing splenomegaly and constitutional symptoms. Common adverse events were gastrointestinal in nature, while hematologic toxicity was limited. However, it was announced that all ongoing clinical trials on pacritinib have been placed on hold by the US Food and Drug Administration in February 2016, due to concerns for increased intracranial hemorrhage and cardiac events. With comprehensive risk-benefit analysis of clinical trial data, the utility of pacritinib in the management of MF may be more clearly defined. Keywords: JAK2, FLT3, myeloproliferative neoplasms, SB1518

  20. The impact of ruxolitinib treatment on inflammation-mediated comorbidities in myelofibrosis and related neoplasms

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Hasselbalch, Hans Carl

    2015-01-01

    The inflammation-mediated comorbidities in myelofibrosis (MF) and related neoplasms (MPNs) likely reflect the concurrent immune deregulation and systemic inflammatory nature of the MPNs, emphasizing the link between chronic systemic inflammation, immune deregulation, and the malignant clone. JAK1......-2 inhibitors in MF-patients reduce constitutional symptoms and splenomegaly, but also taget autoimmune and inflammation-mediated comorbidities....

  1. Imaging of spinal cord compression due to thoracic extramedullary haematopoiesis in myelofibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, A.; Miaux, Y.; Chiras, J. [Department of Neuroradiology `Charcot`, Salpetriere Hospital, Paris (France)

    1997-10-01

    We describe a case of spinal cord compression secondary to extramedullary haematopoiesis in a patient with primary myelofibrosis. We show that MRI should be the procedure of choice for patients suspected of this condition. Furthermore, it could be of value for assessing the extent of cord compression, planning radiotherapy and for follow-up. (orig.). With 2 figs.

  2. The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries

    DEFF Research Database (Denmark)

    Abelsson, J; Merup, M; Birgegård, G

    2012-01-01

    Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups a...

  3. Thrombospondin-1 is not the major activator of TGF-β1 in thrombopoietin-induced myelofibrosis

    DEFF Research Database (Denmark)

    Evrard, Solène; Bluteau, Olivier; Tulliez, Micheline;

    2011-01-01

    -β1 activation, we investigated the role of TSP-1 in the TPO(high) murine model of myelofibrosis. Two groups of engrafted mice, WT TPO(high) and Tsp-1-null TPO(high), were constituted. All mice developed a similar myeloproliferative syndrome and an increase in total TGF-β1 levels in the plasma...... of TGF-β1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment....

  4. Assessment of Liver and Spleen Stiffness in Patients With Myelofibrosis Using FibroScan and Shear Wave Elastography.

    Science.gov (United States)

    Webb, Muriel; Shibolet, Oren; Halpern, Zamir; Nagar, Meital; Amariglio, Ninette; Levit, Stella; Steinberg, David M; Santo, Erwin; Salomon, Ophira

    2015-09-01

    Liver stiffness and spleen stiffness in patients with myelofibrosis have traditionally been assessed through manual palpation and thus influenced by interobserver variability. In this article, for the first time, liver stiffness and spleen stiffness of patients with myelofibrosis were evaluated through FibroScan and shear wave elastography (SWE). Nine patients with myelofibrosis comprised the study group. They were compared with 11 patients with liver cirrhosis and 8 healthy volunteers. Before the FibroScan study, all patients underwent ultrasound study to delineate the left intercostal space for validated measurements. In patients with myelofibrosis, the mean stiffness of the spleen was 41.3 and 32.9 kilopascals (kPa) through FibroScan and SWE, respectively. The mean stiffness of the liver was 7.8 kPa through FibroScan and 10.4 kPa through SWE. The stiffness of the spleen in patients with cirrhosis was even higher, reaching a mean of 58.5 kPa through FibroScan and 40.5 kPa through SWE. The means were considerably lower among the healthy controls (13.5 and 18.1 kPa, respectively). The correlation between spleen stiffness among the patients with cirrhosis is negative and opposite in direction (r = -0.35) in comparison with the patients with myelofibrosis (r = 0.78). Among the patients with liver cirrhosis and myelofibrosis, spleen size was weakly related to spleen stiffness as assessed through SWE (r = 0.49) but had almost no relation to the FibroScan measure (r = 0.13). The FibroScan and SWE of the spleen have little ability to distinguish between the patients with myelofibrosis and cirrhosis, but they do differentiate both patient groups from the healthy controls. The stiffness of spleen and liver as measured through FibroScan and SWE was not correlated to the longevity of myelofibrosis.

  5. Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.

    Science.gov (United States)

    Dolgikh, T Yu; Domnikova, N P; Tornuev, Yu V; Vinogradova, E V; Krinitsyna, Yu M

    2017-02-01

    Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

  6. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

    Science.gov (United States)

    Flanagan, Sarah E; Haapaniemi, Emma; Russell, Mark A; Caswell, Richard; Lango Allen, Hana; De Franco, Elisa; McDonald, Timothy J; Rajala, Hanna; Ramelius, Anita; Barton, John; Heiskanen, Kaarina; Heiskanen-Kosma, Tarja; Kajosaari, Merja; Murphy, Nuala P; Milenkovic, Tatjana; Seppänen, Mikko; Lernmark, Åke; Mustjoki, Satu; Otonkoski, Timo; Kere, Juha; Morgan, Noel G; Ellard, Sian; Hattersley, Andrew T

    2014-08-01

    Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

  7. Treatment and management of myelofibrosis in the era of JAK inhibitors [Corrigendum

    Directory of Open Access Journals (Sweden)

    Keohane C

    2013-10-01

    Full Text Available Keohane C, Radia DH, Harrison CN. Biologics: Targets and Therapy. 2013;7:189–198. On page 193 note that the paragraph beginning "Pacritinib (SB1518; Cell Technology, Inc, Mountain View, CA, USA is a JAK2 and FLT3 inhibitor currently being evaluated at a dose of 400 mg daily in a Phase II study (N=34 that included patients with low platelet counts (<50 × 109/L." should have been "Pacritinib (SB1518; Cell Therapeutics, Inc, Seattle, WA, USA is a JAK2 and FLT3 inhibitor which was evaluated at a dose of 400 mg daily in a Phase II study (N=34 that included patients with low platelet counts (<50 × 109/L." On page 193 in the same paragraph note that "Post-Essential Thrombocythemia Myelofibrosis: PERSIST." should have been "Post-Essential Thrombocythemia Myelofibrosis-1: PERSIST-1."Read the original article

  8. Unemployment and early cause-specific mortality: a study based on the Swedish twin registry

    DEFF Research Database (Denmark)

    Voss, Margaretha; Nylén, Lotta; Floderus, Birgitta

    2004-01-01

    of sleeping pills or tranquilizers, and serious or long-lasting illness tended to strengthen the association between unemployment and early mortality. CONCLUSIONS: An increased risk of death from external causes implies a need for support for those experiencing unemployment, particularly susceptible...

  9. Intense splenic 99mTc-MDP uptake in a patient with myelofibrosis.

    Science.gov (United States)

    Chen, Ming; Liu, Chun; Yang, Jigang

    2013-12-01

    99mTc-MDP bone scan was performed in a 49-year-old woman with breast cancer. Whole-body bone scan showed multiple foci of increased MDP activity in the bone and intense splenic 99mTc-MDP uptake. Initial bone marrow aspiration in multiple locations yielded no blood cells. A subsequent bone marrow biopsy in the left anterior superior iliac spine showed myelofibrosis in addition to the known bone metastasis.

  10. Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

    Directory of Open Access Journals (Sweden)

    Adam Stelling

    2015-12-01

    Full Text Available Primary myelofibrosis (PMF, per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7. Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF, erythroid markers (hemoglobin and E-cadherin, and lymphoid markers (CD3, CD19, and TdT. Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and

  11. Death by unnatural causes during childhood and early adulthood in offspring of psychiatric inpatients

    DEFF Research Database (Denmark)

    Webb, Roger; Pickles, Andrew R.; Appleby, Louis

    2007-01-01

    MEASURES: Deaths from all natural causes and all unnatural causes, specifically, accidents, homicides, suicides, and undetermined causes. RESULTS: The highest observed relative risk (RR) was for homicide in young and older children with affected mothers or fathers. Homicides were between 5 and 10 times......-verdict deaths by poisoning were higher than for such deaths occurring by other means. CONCLUSIONS: Almost 99% of children studied survived to their mid-20s. However, they were more vulnerable to death from unnatural causes, notably, homicide during childhood and suicide in early adulthood. Further research......-fold to 3-fold higher risk of suicide. In almost one fourth of the suicides, there was a history of parental admission. Young adults with 2 previously admitted parents were 6 times more likely to kill themselves than were their peers in the general population. Relative risk of suicide or open...

  12. Reversible bone marrow aplasia induced by pegylated interferon-α-2a therapy in a patient with primary myelofibrosis.

    Science.gov (United States)

    Mainali, Naba R; Bhatt, Vijaya R; Kedia, Shiksha; Krishnamurthy, Jairam; Wake, Laura M; Akhtari, Mojtaba

    2014-10-01

    Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-α-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Ferrokinetic study of splenic erythropoiesis: Relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y. (Univ. of Liege (Belgium))

    1989-10-01

    Splenic erythropoiesis was demonstrated by surface counting of {sup 59}Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis (1) is encountered in a variety of clinical conditions; (2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; (3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and (4) can be evaluated in a semiquantitative manner by surface counting.

  14. Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis.

    Science.gov (United States)

    Robin, Marie; Porcher, Raphael; Wolschke, Christine; Sicre de Fontbrune, Flore; Alchalby, Haefaa; Christopeit, Maximilian; Cassinat, Bruno; Zabelina, Tatjana; Peffault de Latour, Régis; Ayuk, Francis; Socié, Gérard; Kröger, Nicolaus

    2016-07-01

    Allogeneic hematopoietic stem cell transplantation remains the sole curative option for myelofibrosis. Many transplantation recipients receive a reduced-intensity conditioning (RIC) regimen owing to age or comorbidities; however, there is little published evidence to guide the choice of RIC regimen. In this study, we compared outcomes in patients who received 1 of 2 frequently used RIC regimens for patients with myelofibrosis: fludarabine-busulfan (FB) and fludarabine-melphalan (FM). A total of 160 patients underwent a RIC allograft procedure (FB group, n = 105; FM group, n = 55). We have developed a complex statistical model involving weighting and adjustment to permit comparison between these 2 groups. After weighting, the incidence of acute graft-versus-host disease (GVHD) was 62% in the FM group and 31% in the FB group (P = .001), and the corresponding incidence of chronic GVHD was 49% and 53%, respectively. The 7-year progression-free survival was were 52% in the FM group versus 33% in the FB group, and the 7-year overall survival rate 52% in the FM group versus 59% in the FB group. Nonrelapse mortality (NRM) was 43% in the FM group and 31% in the FB group. Multivariable analyses revealed no significant differences in PFS between the 2 groups; however, the relapse rate was significantly lower in the FM group (hazard ratio, 9.21; P = .008), whereas a trend toward reduced NRM was seen in the FB group (hazard ratio, 0.51; P = .068). In conclusion, both regimens appear to be efficient in mediating disease control and can be used to successfully condition patients with myelofibrosis. The FM regimen appears to induce more NRM than the FB regimen, but with augmented control of disease, leading to comparable overall survival rates for both regimens.

  15. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    Science.gov (United States)

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  16. Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis

    Directory of Open Access Journals (Sweden)

    Barosi G

    2015-05-01

    Full Text Available Giovanni Barosi,1 Vittorio Rosti,1 Robert Peter Gale2 1Center for the Study of Myelofibrosis, IRCCS Policlinico S Matteo Foundation, Pavia, Italy; 2Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK Abstract: The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE approach by evaluating five dimensions of evidence: (1 overall risk of bias, (2 imprecision, (3 inconsistency, (4 indirectness, and (5 publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low. In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it

  17. Mayor Erythropoietic Response after Deferasirox Treatment in a Transfusion-Dependent Anemic Patient with Primary Myelofibrosis

    Science.gov (United States)

    Lisette, Del Corso; Enrico, Balleari; Eleonora, Arboscello; Riccardo, Ghio; Manlio, Mencoboni; Omar, Racchi

    2013-01-01

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm frequently complicated by transfusion dependent anemia. Both anemia and transfusion-dependence are associated with a poor outcome, at least in part because of toxic effects of iron overload (IOL). Iron-chelating therapy (ICT) is increasingly used in order to prevent IOL in this setting. Here, we describe the case of a 73-year-old man affected by PMF and severe transfusion-dependent anemia who experienced a dramatic erythroid response after being treated with deferasirox to prevent IOL. PMID:24307957

  18. Cytogenetic studies in twelve patients with primary myelofibrosis and myeloid metaplasia.

    Science.gov (United States)

    Smadja, N; Krulik, M; de Gramont, A; Sirinelli, A; Brissaud, P; Dray, C; Audebert, A A; Debray, J

    1987-01-01

    Chromosome studies on bone marrow and/or peripheral blood cells without phytohemagglutinin were performed on 12 patients with primary myelofibrosis with myeloid meta-plasia (PMMM) between 1980 and 1984. Abnormal clones were found in six patients (50%). In five cases the abnormal clone involved the long arm of chromosome #7, two of which also had partial trisomy of chromosome #1 and trisomy of 9. Additional abnormalities involving chromosomes #3, #5, #11, #13, #15, and #21 were each found once. Review of the literature showed few studies on the cytogenetics of PMMM. No specific chromosomal pattern can be established; however, abnormalities described are nonrandom.

  19. Mayor erythropoietic response after deferasirox treatment in a transfusion-dependent anemic patient with primary myelofibrosis.

    Science.gov (United States)

    Lisette, Del Corso; Enrico, Balleari; Eleonora, Arboscello; Riccardo, Ghio; Manlio, Mencoboni; Omar, Racchi

    2013-01-01

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm frequently complicated by transfusion dependent anemia. Both anemia and transfusion-dependence are associated with a poor outcome, at least in part because of toxic effects of iron overload (IOL). Iron-chelating therapy (ICT) is increasingly used in order to prevent IOL in this setting. Here, we describe the case of a 73-year-old man affected by PMF and severe transfusion-dependent anemia who experienced a dramatic erythroid response after being treated with deferasirox to prevent IOL.

  20. Mayor Erythropoietic Response after Deferasirox Treatment in a Transfusion-Dependent Anemic Patient with Primary Myelofibrosis

    Directory of Open Access Journals (Sweden)

    Del Corso Lisette

    2013-01-01

    Full Text Available Primary myelofibrosis (PMF is a myeloproliferative neoplasm frequently complicated by transfusion dependent anemia. Both anemia and transfusion-dependence are associated with a poor outcome, at least in part because of toxic effects of iron overload (IOL. Iron-chelating therapy (ICT is increasingly used in order to prevent IOL in this setting. Here, we describe the case of a 73-year-old man affected by PMF and severe transfusion-dependent anemia who experienced a dramatic erythroid response after being treated with deferasirox to prevent IOL.

  1. DECREASED REACTIVITY TO ANXIOLYTICS CAUSED BY EARLY PROTEIN MALNUTRITION IN RATS

    OpenAIRE

    Almeida, Sebastião Sousa; Oliveira,Luiz Marcellino de; Frederico G. Graeff

    2016-01-01

    In order to investigate whether early malnutrition causes lasting changes in the reactivity to anxiolytic drugs, rat dams lactation (21 days) and pops after weaning until the 49th day of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats), from day 50 on all animals ate the same balanced diet. Experiments started on the 91st day. Rats deprived for 22 hours drank water containing either 1.8% or 2.7% sodium chloride for 30 min in a test cha...

  2. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis

    Science.gov (United States)

    Buhr, Thomas; Hebeda, Konnie; Kaloutsi, Vassiliki; Porwit, Anna; Van der Walt, Jon; Kreipe, Hans

    2012-01-01

    Background The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. Design and Methods To assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. Results Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. Conclusions World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone. PMID:22058215

  3. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Directory of Open Access Journals (Sweden)

    Yi-Chu Liao

    Full Text Available Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  4. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Liao, Yi-Chu; Liu, Yo-Tsen; Tsai, Pei-Chien; Chang, Chia-Ching; Huang, Yen-Hua; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT) type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive. Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability. GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  5. GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.

    Science.gov (United States)

    Papandreou, Apostolos; McTague, Amy; Trump, Natalie; Ambegaonkar, Gautam; Ngoh, Adeline; Meyer, Esther; Scott, Richard H; Kurian, Manju A

    2016-04-01

    The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra.

  6. Efficient runner safety assessment during early design phase and root cause analysis

    Science.gov (United States)

    Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

    2012-11-01

    Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

  7. Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study

    NARCIS (Netherlands)

    Guglielmelli, Paola; Biamonte, Flavia; Rotunno, Giada; Artusi, Valentina; Artuso, Lucia; Bernardis, Isabella; Tenedini, Elena; Pieri, Lisa; Paoli, Chiara; Mannarelli, Carmela; Fjerza, Rajmonda; Rumi, Elisa; Stalbovskaya, Viktoriya; Squires, Matthew; Cazzola, Mario; Manfredini, Rossella; Harrison, Claire; Tagliafico, Enrico; Vannucchi, Alessandro M; Kluin-Nelemans, H.C.

    2014-01-01

    The JAK1/JAK2 inhibitor ruxolitinib produced significant reductions in splenomegaly and symptomatic burden and improved survival in patients with myelofibrosis (MF), irrespective of their JAK2 mutation status, in 2 phase III studies against placebo (COMFORT-I) and best available therapy

  8. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

    Science.gov (United States)

    Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

    2015-03-01

    Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

  9. Acute Panmyelosis with Myelofibrosis - A Rare Subtype of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Tathagata Chatterjee

    2013-06-01

    Full Text Available One case of acute panmyelosis with myelofibrosis (APMF is being reported. A 45 year old male presented with abrupt onset of rapidly progressing low backache, weakness and pancytopenia. On examination there was no organomegaly. Peripheral blood examination revealed normocytic normochromic red blood cells with 10% circulating blasts. Flowcytometric examination of peripheral blood revealed blasts which were positive for CD 34 ,HLA- DR and myeloid associated antigens (i.e. CD13 and CD33.Blasts were negative for anti MPO. Bone marrow aspirate resulted in a dry tap. Bone marrow biopsy revealed panmyeloid proliferation with scattered blasts which were CD 34 positive on imunohistochemistry and negative for anti MPO. Reticulin stain showed grade III myelofibrosis (WHO. Differential diagnosis considered included AML-M7, MDS-RAEB II and AML with myelodysplasia . He was started on chemotherapy [idarubicin and cytarabine; 3+7 induction regimen followed by three cycles of HIDAC (High dose cytosine arabinoside] after which patient was in complete morphological remission with markedly reduced bone marrow fibrosis. He is now being worked up for allogeneic stem cell transplantation. Patient is asymptomatic at eight months of diagnosis. In conclusion these patients should be managed aggressively with AML therapy and this case report reaffirms the fact that APMF is subtype of AML.

  10. Treatment and management of myelofibrosis in the era of JAK inhibitors

    Directory of Open Access Journals (Sweden)

    Keohane C

    2013-08-01

    Full Text Available Clodagh Keohane, Deepti H Radia, Claire N HarrisonDepartment of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UKAbstract: Myelofibrosis (MF can present as a primary disorder or evolve from polycythemia vera (PV or essential thrombocythemia (ET to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT, the use of cytoreductive agents (ie, hydroxyurea, splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs, androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.Keywords: myelofibrosis, ruxolitinib, JAK inhibitor

  11. Long-term results of prednisone treatment for the anemia of myelofibrosis.

    Science.gov (United States)

    Hernández-Boluda, Juan-Carlos; Martínez-Trillos, Alejandra; García-Gutiérrez, Valentín; Ferrer-Marín, Francisca; Xicoy, Blanca; Alvarez-Larrán, Alberto; Kerguelen, Ana; Barba, Pere; Gómez, Montse; Herrera, Juan-Carlos; Correa, Juan-Gonzalo; Cervantes, Francisco

    2016-01-01

    This study has retrospectively analyzed the efficacy of single-agent prednisone, usually given after failure of other therapies, in 30 patients with myelofibrosis (MF) and severe anemia. Initial dose was 0.5-1 mg/kg daily, with tapering to the minimum effective dose in responders. Twelve patients (40%) achieved anemia response according to the revised International Working Group for Myelofibrosis Research and Treatment criteria, after a median time of 1.1 months on treatment. Median response duration was 12.3 months. Patients with constitutional symptoms or > 2% circulating blasts had a trend for a lower response rate. A platelet increase > 50 × 10(9)/L was observed in three out of 11 patients with baseline counts prednisone start was significantly longer in anemia responders (5.0 years, 95% CI = 3.5-6.5, vs 1.5 years, 95% CI = 0.2-2.8; p = 0.002). Prednisone can improve the anemia and thrombocytopenia in selected MF patients after failure to standard therapies.

  12. Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis

    Science.gov (United States)

    Wei, Max; Ren, Xiubao; Shao, Zonghong; Zhang, Ling; Levine, Ross L.; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo. TGFβ production by malignant megakaryocytes plays a definitive role promoting myelofibrosis in MPNs. However, TGFβ was equally expressed by MSCs derived from MPLWT and MPLW515L expressing mice and the addition of neutralizing anti-TGFβ antibody only partially reduced collagen secretion in vitro. Interestingly, profibrotic MSCs displayed increased levels of pSmad3 and pSTAT3 suggesting that inflammatory mediators cooperating with the TGFβ-receptor signaling may maintain the aberrant phenotype ex vivo. FGFb is a known suppressor of TGFβ signaling. Reduced collagen deposition by FGFb-treated MSCs derived from MPLW515L mice suggests that the activating pathway is vulnerable to this suppressive mediator. Therefore, our findings have implications for the future investigation of therapies to reverse fibrosis in MPNs. PMID:28135282

  13. Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors.

    Science.gov (United States)

    Bregante, Stefania; Dominietto, Alida; Ghiso, Anna; Raiola, Anna Maria; Gualandi, Francesca; Varaldo, Riccardo; Di Grazia, Carmen; Lamparelli, Teresa; Luchetti, Silvia; Geroldi, Simona; Casarino, Lucia; Pozzi, Sarah; Tedone, Elisabetta; Van Lint, Maria Teresa; Galaverna, Federica; Barosi, Giovanni; Bacigalupo, Andrea

    2016-02-01

    This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen.

  14. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients.

    Science.gov (United States)

    Polverelli, Nicola; Breccia, Massimo; Benevolo, Giulia; Martino, Bruno; Tieghi, Alessia; Latagliata, Roberto; Sabattini, Elena; Riminucci, Mara; Godio, Laura; Catani, Lucia; Nicolosi, Maura; Perricone, Margherita; Sollazzo, Daria; Colafigli, Gioia; Campana, Anna; Merli, Francesco; Vitolo, Umberto; Alimena, Giuliana; Martinelli, Giovanni; Lewis, Russell E; Vianelli, Nicola; Cavo, Michele; Palandri, Francesca

    2017-01-01

    Although infectious complications represent a relevant cause of morbidity and mortality in patients with myelofibrosis (MF), little is known about their incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507 MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers, to define the epidemiology of infections and describe the impact of ruxolitinib (RUX) treatment. Overall, 112 patients (22%) experienced 160 infectious events (grade 3-4, 45%) for an incidence rate of 3.9% per patient-year. Infections were mainly bacterial (78%) and involving the respiratory tract (52% of cases). Also, viral (11%) and fungal infections (2%) were recorded. Overall, infections were fatal in 9% of the cases. Among baseline features, high/intermediate-2 IPSS category (HR 1.8, 95%CI:1.2-2.7; P = 0.02) and spleen length ≥10 cm below left costal margin (HR 1.6, 95%CI:1.1-2.5; P = 0.04) were associated with higher infectious risk in multivariate analysis. Overall, the rate of infections was higher in the cohort of 128 RUX-treated patients (44% vs. 20%, P < 0.001). In conclusion, IPSS-category and splenomegaly, emerged as the main risk factors for infections in MF. RUX-treated patients experienced significantly more infection episodes; however, future prospective studies are needed to isolate the confounding contribution of other risk factors such as disease stage. Am. J. Hematol. 92:37-41, 2017. © 2016 Wiley Periodicals, Inc.

  15. Climate Cycling on Early Mars Caused by the Carbonate-Silicate Cycle

    Science.gov (United States)

    Kasting, J. F.; Batalha, N. E.; Haqq-Misra, J. D.; Kopparapu, R.

    2016-12-01

    For decades, scientists have tried to explain the evidence for fluvial activity on early Mars, but a consensus has yet to emerge regarding the mechanism for producing it. One hypothesis suggests early Mars was warmed by a thick greenhouse atmosphere [1]. Another suggests early Mars was generally cold but was warmed occasionally by impacts or by episodes of enhanced volcanism [2,3], with warming possibly extended by cirrus clouds [4]. These latter hypotheses struggle to produce the amounts of rainfall needed to form the martian valleys, but are consistent with inferred low rates of weathering compared to Earth. We suggest that both schools of thought are partly correct. Mars experienced dramatic climate cycles with extended periods of glaciation punctuated by warm periods lasting up to 10 Myr [5]. Cycles of repeated glaciation and deglaciation occurred because stellar insolation was low, and because CO2 outgassing could not keep pace with CO2 consumption by silicate weathering followed by deposition of carbonates. In order to deglaciate early Mars, substantial outgassing of molecular hydrogen from Mars' reduced crust and mantle was also required, as our own climate model is unable to do this without adding some greenhouse warming from H2 [6,7]. Our hypothesis can be tested by future Mars exploration that better establishes the time scale for valley formation. References: [1] Pollack JB, Kasting JF, Richardson SM, Poliakoff K. 1987. Icarus 71: 203-24 [2] Halevy I, Head JW. 2014. Nature Geoscience 7: 865-8 [3] Segura TL, Toon OB, Colaprete A, Zahnle K. 2002. Science 298: 1977-80 [4] Urata RA, Toon OB. 2013. Icarus 226: 229-50 [5] Batalha NE, Kopparapu RK, Haqq-Misra JD, Kasting JF. submitted. Climate cycling on early Mars caused by the carbonate-silicate cycle. EPSL [6] Ramirez RM, Kopparapu R, Zugger ME, Robinson TD, Freedman R, Kasting JF. 2014. Nature Geosci 7: 59-63 [7] Batalha N, Domagal-Goldman SD, Ramirez R, Kasting JF. 2015. Icarus 258: 337-49

  16. De novo mutations in HCN1 cause early infantile epileptic encephalopathy

    DEFF Research Database (Denmark)

    Nava, Caroline; Dalle, Carine; Rastetter, Agnès

    2014-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations...... in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino...... toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans....

  17. Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

    Directory of Open Access Journals (Sweden)

    Akira Yabuki

    2011-01-01

    Full Text Available A 10-year-old spayed female Papillon weighing 4.0 kg presented with a history of persistent hematuria and pollakiuria. Concurrent bladder calculi, a mammary gland tumor, and nonazotemic early stage of chronic kidney disease with contracted kidneys were noted in this dog. The dog underwent cystectomy, unilateral mastectomy, and intraoperative renal biopsy. On the basis of histopathological analysis of renal biopsy results, it was suspected that renal injury of the dog was caused by persistent hypertension, and a follow-up examination revealed severe hypertension. The dog was treated with a combination of an angiotensin-converting enzyme inhibitor and calcium channel blocker. The treatment produced a good outcome in the dog, and there has been no progression of the chronic kidney disease for over 2 years.

  18. Intelligence in early adulthood and mortality from natural and unnatural causes in middle-aged Danish men

    DEFF Research Database (Denmark)

    Meincke, Rikke Hodal; Mortensen, Erik Lykke; Avlund, Kirsten;

    2014-01-01

    High intelligence early in life has consistently been associated with decreased mortality, but the mechanisms are still not fully understood. In this cohort study, we examined the association between intelligence in early adulthood and later mortality from natural and unnatural causes taking birth...

  19. Reactivation of Pulmonary Tuberculosis following Treatment of Myelofibrosis with Ruxolitinib

    Directory of Open Access Journals (Sweden)

    Maheen Z. Abidi

    2016-01-01

    Full Text Available Ruxolitinib is widely in use for treatment of myeloproliferative disorders. It causes inhibition of the Janus kinase (JAK signal transducer and activation of transcription (STAT pathway, which plays a key role in the underlying pathophysiology of myeloproliferative diseases. We describe a case of reactivation pulmonary tuberculosis in a retired physician while on treatment with ruxolitinib. We also review the literature on opportunistic infections following use of ruxolitinib. Our case highlights the importance of screening for latent tuberculosis in patients from highly endemic areas prior to start of therapy with ruxolitinib.

  20. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

  1. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Science.gov (United States)

    Zoll, Jan; Erkens Hulshof, Sandra; Lanke, Kjerstin; Verduyn Lunel, Frans; Melchers, Willem J G; Schoondermark-van de Ven, Esther; Roivainen, Merja; Galama, Jochem M D; van Kuppeveld, Frank J M

    2009-05-01

    The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute

  2. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life.

    Directory of Open Access Journals (Sweden)

    Jan Zoll

    2009-05-01

    Full Text Available The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus. In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV and Theiler's murine encephalomyelits virus (TMEV. The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV. The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3 isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible

  3. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis.

    NARCIS (Netherlands)

    Buhr, T.; Hebeda, K.M.; Kaloutsi, V.; Porwit, A.; Walt, J. Van der; Kreipe, H.

    2012-01-01

    BACKGROUND: The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable pro

  4. European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis

    NARCIS (Netherlands)

    Buhr, Thomas; Hebeda, Konnie; Kaloutsi, Vassiliki; Porwit, Anna; Van der Walt, Jon; Kreipe, Hans

    2012-01-01

    Background The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prog

  5. Mutation in noncoding RNA RNU12 causes early onset cerebellar ataxia.

    Science.gov (United States)

    Elsaid, Mahmoud Fawzi; Chalhoub, Nader; Ben-Omran, Tawfeg; Kumar, Pankaj; Kamel, Hussein; Ibrahim, Khalid; Mohamoud, Yasmin; Al-Dous, Eman; Al-Azwani, Iman; Malek, Joel A; Suhre, Karsten; Ross, M Elizabeth; Aleem, Alice Abdel

    2017-01-01

    Exome sequences account for only 2% of the genome and may overlook mutations causing disease. To obtain a more complete view, whole genome sequencing (WGS) was analyzed in a large consanguineous family in which members displayed autosomal recessively inherited cerebellar ataxia manifesting before 2 years of age. WGS from blood-derived genomic DNA was used for homozygosity mapping and a rare variant search. RNA from isolated blood leukocytes was used for quantitative polymerase chain reaction (PCR), RNA sequencing, and comparison of the transcriptomes of affected and unaffected family members. WGS revealed a point mutation in noncoding RNA RNU12 that was associated with early onset cerebellar ataxia. The U12-dependent minor spliceosome edits 879 known transcripts. Reverse transcriptase PCR demonstrated minor intron retention in all of 9 randomly selected RNAs from this group, and RNAseq showed splicing disruption specific to all U12-type introns detected in blood monocytes from affected individuals. Moreover, 144 minor intron-containing RNAs were differentially expressed, including transcripts for 3 genes previously associated with cerebellar neurodegeneration. Interference with particular spliceosome components, including small nuclear RNAs, cause reproducible uniquely distributed phenotypic and transcript-specific effects, making this an important category of disease-associated mutation. Our approach to differential expression analysis of minor intron-containing genes is applicable to other diseases involving altered transcriptome processing. ANN NEUROL 2017;81:68-78. © 2016 American Neurological Association.

  6. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    Science.gov (United States)

    Oláhová, Monika; Hardy, Steven A; Hall, Julie; Yarham, John W; Haack, Tobias B; Wilson, William C; Alston, Charlotte L; He, Langping; Aznauryan, Erik; Brown, Ruth M; Brown, Garry K; Morris, Andrew A M; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M; Bonnen, Penelope E; Prokisch, Holger; Lightowlers, Robert N; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Taylor, Robert W

    2015-12-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels

  7. Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Sand Jette C

    2007-07-01

    Full Text Available Abstract Background X-linked Charcot-Marie Tooth (CMT is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. Methods We describe two novel mutations in the connexin32 gene in two Norwegian families. Results Family 1 had a c.225delG (R75fsX83 which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands. The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s. Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals. Conclusion The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.

  8. Occupational class inequalities in all-cause and cause-specific mortality among middle-aged men in 14 European populations during the early 2000s.

    Directory of Open Access Journals (Sweden)

    Marlen Toch-Marquardt

    Full Text Available This study analyses occupational class inequalities in all-cause mortality and four specific causes of death among men, in Europe in the early 2000s, and is the most extensive comparative analysis of occupational class inequalities in mortality in Europe so far. Longitudinal data, obtained from population censuses and mortality registries in 14 European populations, from around the period 2000-2005, were used. Analyses concerned men aged 30-59 years and included all-cause mortality and mortality from all cancers, all cardiovascular diseases (CVD, all external, and all other causes. Occupational class was analysed according to five categories: upper and lower non-manual workers, skilled and unskilled manual workers, and farmers and self-employed combined. Inequalities were quantified with mortality rate ratios, rate differences, and population attributable fractions (PAF. Relative and absolute inequalities in all-cause mortality were more pronounced in Finland, Denmark, France, and Lithuania than in other populations, and the same countries (except France also had the highest PAF values for all-cause mortality. The main contributing causes to these larger inequalities differed strongly between countries (e.g., cancer in France, all other causes in Denmark. Relative and absolute inequalities in CVD mortality were markedly lower in Southern European populations. We conclude that relative and absolute occupational class differences in all-cause and cause specific mortality have persisted into the early 2000's, although the magnitude differs strongly between populations. Comparisons with previous studies suggest that the relative gap in mortality between occupational classes has further widened in some Northern and Western European populations.

  9. Occupational class inequalities in all-cause and cause-specific mortality among middle-aged men in 14 European populations during the early 2000s.

    Science.gov (United States)

    Toch-Marquardt, Marlen; Menvielle, Gwenn; Eikemo, Terje A; Kulhánová, Ivana; Kulik, Margarete C; Bopp, Matthias; Esnaola, Santiago; Jasilionis, Domantas; Mäki, Netta; Martikainen, Pekka; Regidor, Enrique; Lundberg, Olle; Mackenbach, Johan P

    2014-01-01

    This study analyses occupational class inequalities in all-cause mortality and four specific causes of death among men, in Europe in the early 2000s, and is the most extensive comparative analysis of occupational class inequalities in mortality in Europe so far. Longitudinal data, obtained from population censuses and mortality registries in 14 European populations, from around the period 2000-2005, were used. Analyses concerned men aged 30-59 years and included all-cause mortality and mortality from all cancers, all cardiovascular diseases (CVD), all external, and all other causes. Occupational class was analysed according to five categories: upper and lower non-manual workers, skilled and unskilled manual workers, and farmers and self-employed combined. Inequalities were quantified with mortality rate ratios, rate differences, and population attributable fractions (PAF). Relative and absolute inequalities in all-cause mortality were more pronounced in Finland, Denmark, France, and Lithuania than in other populations, and the same countries (except France) also had the highest PAF values for all-cause mortality. The main contributing causes to these larger inequalities differed strongly between countries (e.g., cancer in France, all other causes in Denmark). Relative and absolute inequalities in CVD mortality were markedly lower in Southern European populations. We conclude that relative and absolute occupational class differences in all-cause and cause specific mortality have persisted into the early 2000's, although the magnitude differs strongly between populations. Comparisons with previous studies suggest that the relative gap in mortality between occupational classes has further widened in some Northern and Western European populations.

  10. SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Albano Francesco

    2012-08-01

    Full Text Available Abstract The molecular pathogenesis underlying the primary myelofibrosis (PMF progression to acute myeloid leukemia (AML is still not well defined. The involvement of microRNA (miRNA is actually helping to shed light on an important issue in the occurrence of myeloproliferative neoplasms (MPNs. However, the role of intronic miRNA, derived from the intron regions of gene transcripts, has never been reported in MPNs. In this study, we describe a PMF case evolved to AML with a t(12;18(p13;q12 rearrangement showing the downregulation of the intronic miR_4319 and the overexpression of its host gene, SET binding protein (SETBP1. A possible molecular mechanism regulating the PMF progression to AML is discussed.

  11. Janus kinase inhibition and its effect upon the therapeutic landscape for myelofibrosis: from palliation to cure?

    Science.gov (United States)

    Harrison, Claire; Verstovsek, Srdan; McMullin, Mary F; Mesa, Ruben

    2012-05-01

    Following the discovery of the Janus kinase (JAK) 2 V617F mutation in 2005 the explosion of research and drug development activity has not only advanced our understanding of the pathogenesis of myeloproliferative neoplasms (MPNs) but also triggered debate about classification, allowed revised diagnostic and response criteria, provided a target for treatment and a mode of monitoring its success. These changes and the resultant clinical research are discussed in this article where we argue that discovery of the JAK2 V617F mutation has signalled the much delayed change in therapeutic paradigm for myelofibrosis and possibly other MPNs from palliation and allowing us to move closer to, but not yet attain, a cure.

  12. Bone geometry, bone mineral density, and micro-architecture in patients with myelofibrosis

    DEFF Research Database (Denmark)

    Farmer, Sarah; Vestergaard, Hanne; Hansen, Stinus

    2015-01-01

    compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone...... mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen......Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry...

  13. Early life origins of all-cause and cause-specific disability pension: findings from the Helsinki Birth Cohort Study.

    Directory of Open Access Journals (Sweden)

    Mikaela B von Bondorff

    Full Text Available There is some evidence linking sub-optimal prenatal development to an increased risk of disability pension (DP. Our aim was to investigate whether body size at birth was associated with transitioning into all-cause and cause-specific DP during the adult work career.10 682 people born in 1934-44 belonging to the Helsinki Birth Cohort Study had data on birth weight extracted from birth records, and on time, type and reason of retirement between 1971 and 2011 extracted from the Finnish Centre for Pensions.Altogether 21.3% transitioned into DP during the 40-year follow-up, mainly due to mental disorders, musculoskeletal disorders and cardiovascular disease. Average age of transitioning into DP was 51.3 (SD 8.4 for men and 52.2 (SD 7.6 for women. Cohort members who did not transition into DP retired 10 years later on average. Among men, higher birth weight was associated with a lower hazard of transitioning into DP, adjusted hazard ratio (HR being 0.94 (95% confidence interval [CI] 0.88-0.99 for 1 SD increase in birth weight. For DP due to mental disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non-significant trend was found for DP due to cardiovascular disease. Among women there were no associations between body size at birth and all-cause DP (p for interaction gender*birth weight on DP p = 0.007.Among men disability pension, particularly due to mental disorders, may have its origins in prenatal development. Given that those who retire due to mental health problems are relatively young, the loss to the workforce is substantial.

  14. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes

    Directory of Open Access Journals (Sweden)

    Mughal TI

    2014-01-01

    Full Text Available Tariq I Mughal,1 Kris Vaddi,2 Nicholas J Sarlis,2 Srdan Verstovsek31Tufts University School of Medicine, Boston, MA, 2Incyte Corporation, Wilmington, DE, 3Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Myelofibrosis (MF is a rare chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of MF include splenomegaly, consequent to extramedullary hematopoiesis, cytopenias, and an array of potentially debilitating abdominal and constitutional symptoms. Dysregulated Janus kinase (JAK-signal transducer and activator of transcription signaling underlies secondary disease-associated effects in MF, such as myeloproliferation, bone marrow fibrosis, constitutional symptoms, and cachexia. Common fatal complications of MF include transformation to acute leukemia, thrombohemorrhagic events, organ failure, and infections. Potential complications from hepatosplenomegaly include portal hypertension and variceal bleeding, whereas extramedullary hematopoiesis outside the spleen and liver – depending on the affected organ – may result in intracranial hypertension, spinal cord compression, pulmonary hypertension, pleural effusions, lymphadenopathy, skin lesions, and/or exacerbation of abdominal symptoms. Although allogeneic stem cell transplantation is the only potentially curative therapy, it is suitable for few patients. The JAK1/JAK2 inhibitor ruxolitinib is effective in improving splenomegaly, MF-related symptoms, and quality-of-life measures. Emerging evidence that ruxolitinib may be associated with a survival benefit in intermediate- or high-risk MF suggests the possibility of a disease-modifying effect. Consequently, ruxolitinib could provide a treatment backbone to which other (conventional and novel

  15. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

    Science.gov (United States)

    Marty, Caroline; Pecquet, Christian; Nivarthi, Harini; El-Khoury, Mira; Chachoua, Ilyas; Tulliez, Micheline; Villeval, Jean-Luc; Raslova, Hana; Kralovics, Robert; Constantinescu, Stefan N; Plo, Isabelle; Vainchenker, William

    2016-03-10

    Frameshift mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and myelofibrosis patients. To address the contribution of the CALR mutants to the pathogenesis of myeloproliferative neoplasms, we engrafted lethally irradiated recipient mice with bone marrow cells transduced with retroviruses expressing these mutants. In contrast to wild-type CALR, CALRdel52 (type I) and, to a lesser extent, CALRins5 (type II) induced thrombocytosis due to a megakaryocyte (MK) hyperplasia. Disease was transplantable into secondary recipients. After 6 months, CALRdel52-, in contrast to rare CALRins5-, transduced mice developed a myelofibrosis associated with a splenomegaly and a marked osteosclerosis. Monitoring of virus-transduced populations indicated that CALRdel52 leads to expansion at earlier stages of hematopoiesis than CALRins5. However, both mutants still specifically amplified the MK lineage and platelet production. Moreover, a mutant deleted of the entire exon 9 (CALRdelex9) did not induce a disease, suggesting that the oncogenic property of CALR mutants was related to the new C-terminus peptide. To understand how the CALR mutants target the MK lineage, we used a cell-line model and demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1. We confirmed in c-mpl- and tpo-deficient mice that expression of Mpl, but not of Tpo, was essential for the CALR mutants to induce thrombocytosis in vivo, although Tpo contributes to disease penetrance. Thus, CALR mutants are sufficient to induce thrombocytosis through MPL activation. © 2016 by The American Society of Hematology.

  16. A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Burton, Mark; Thomassen, Mads;

    2016-01-01

    been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling...... was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO...

  17. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis

    Science.gov (United States)

    Gupta, Vikas; Mesa, Ruben A.; Deininger, Michael W.N.; Rivera, Candido E.; Sirhan, Shireen; Brachmann, Carrie Baker; Collins, Helen; Kawashima, Jun; Xin, Yan; Verstovsek, Srdan

    2017-01-01

    Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post–polycythemia vera/post–essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058). PMID:27634203

  18. Primary Myelofibrosis Presenting as Extramedullary Hematopoiesis in a Transplanted Liver Graft: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ghulam Rehman Mohyuddin

    2016-01-01

    Full Text Available Primary myelofibrosis (PMF commonly results in extramedullary hematopoiesis (EMH in the spleen and liver as well as a variety of other organs. We present a first report of a unique presentation of PMF in a liver transplant recipient patient as EMH in the transplanted liver graft. A 76-year-old man with history of cryptogenic cirrhosis received cadaveric liver transplantation in 1996. He maintained a normal graft function and stable hematologic parameters until 2013 when he presented with anemia and progressive fatigue. Extensive work-up did not identify the etiology of the recent decline in his hemoglobin; thus a liver biopsy was done which showed findings of EMH within the sinusoids with increased megakaryocytes, some with atypical morphology. A BM biopsy revealed a hypercellular marrow, moderately increased reticulin fibrosis, and features consistent with primary myelofibrosis. Abdominal imaging showed a normal-size spleen and did not identify any sites of EMH outside of the liver. The diagnosis of myelofibrosis was thus made, and this case demonstrated predominant tropism to a transplanted liver graft with absence of EMH elsewhere. We would thus like to emphasize that findings of EMH in subjects with no preexisting hematologic neoplasm should warrant close follow-up and assessment.

  19. [Serological diagnosis of an infestation caused by the early developmental stages of botfly larvae (Oedemagena tarandi) in reindeer].

    Science.gov (United States)

    Solopov, N V; Kalinina, N G

    1984-01-01

    Undertaken investigations have shown that the antigen prepared from larvae of O. tarandi is diagnostically effective and stricktly specific only to this infection in the reaction of indirect hemagglutination (RIHA). The experiments have proved the possibility of practical use of RIHA as a principal method of early diagnosis of infection of reindeer caused by O. tarandi.

  20. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

    NARCIS (Netherlands)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2015-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflamma

  1. Palliative splenic irradiation in primary and post PV/ET myelofibrosis: outcomes and toxicity of three radiation schedules

    Directory of Open Access Journals (Sweden)

    Mario Federico

    2009-05-01

    Full Text Available Splenectomy and splenic irradiation (SI are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF. SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2-1.4 Gy, and total dose varied from 2-10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopenias occurred in 13% of radiation courses. Furthermore patients were divided in three groups according to the radiation dose they received: 6 patients in the low-dose group (LDG received a normalized dose of 1.67 Gy; 4 patients in the intermediate-dose group (IDG received a normalized dose 4.37 Gy; the remaining 4 patients in the high-dose group (HDG received a normalized dose of 9.2 Gy. Subgroup analysis showed that if no differences in terms of treatment’s efficacy were seen among dose groups, hematologic toxicity rates distributed differently. Severe cytopenias occurred in 50% of courses in the HDG, and in the 14.3% and in 0% of the IDG and LDG respectively. Spleen reduction and pain relief lasted for a median of 5.5 months in all groups. Due to the efficacy and tolerability of the low-dose irradiation 4 patients from the LDG and IDG were retreated and received on the whole 12 RT courses. Multiple retreatments did not show decremental trends in terms of rates of response to radiation nor in terms of duration of clinical response. Moreover, retreatment courses did not cause an increased rate of adverse effects and none of the retreated patients experienced severe hematologic toxicities. The average time of clinical benefit in retreated patients was much longer

  2. Abnormal P-selectin localization during megakaryocyte development determines thrombosis in the gata1low model of myelofibrosis.

    Science.gov (United States)

    Zetterberg, Eva; Verrucci, Maria; Martelli, Fabrizio; Zingariello, Maria; Sancillo, Laura; D'Amore, Emanuela; Rana, Rosa Alba; Migliaccio, Anna Rita

    2014-01-01

    Patients with primary myelofibrosis have increased risk for bleeding and thrombosis. It is debated whether propensity to thrombosis is due to increased numbers of platelet microparticles and/or to pathological platelet-neutrophil interactions. Platelet neutrophil interactions are mediated by P-selectin and even though the megakaryocytes of myelofibrosis patients express normal levels of P-selectin, it remains abnormally localized to the demarcation membrane system rather than being assembled into the α-granules in platelets. Mice carrying the hypomorphic Gata1(low) mutation express the same megakaryocyte abnormalities presented by primary myelofibrosis patients, including abnormal P-selectin localization to the DMS and develop with age myelofibrosis, a disease that closely resembles human primary myelofibrosis. Whether these mice would also develop thrombosis has not been investigated as yet. The aim of this study was to determine whether Gata1(low) mice would develop thrombosis with age and, in this case, the role played by P-selectin in the development of the trait. To this aim, Gata1(low) mice were crossed with P-sel(null) mice according to standard genetic protocols and Gata1(low)P-sel(wt), Gata1(low)P-sel(null) and Gata1(WT)P-sel(null) or Gata1(wt)P-sel(wt) (as controls) littermates obtained. It was shown that platelet counts, but not hematocrit, are reduced in Gata1(low) mice. Moreover, platelet microparticles are reduced in Gata1(low) mice and P-selectin positive platelet microparticles were not found. To determine the phenotypic implications of the different mutations, bleeding time was estimated by a tail cut procedure. Mutant mice were sacrificed and presence of thrombosis was determined by immunohistological staining of organs. Gata1(low) mice with or without the P-selectin null trait had a prolonged bleeding time compared to wild type mice. However, in Gata1(low) mice significantly higher frequency of thrombotic events was seen in adult and old Gata1

  3. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    NARCIS (Netherlands)

    Kroger, N.; Holler, E.; Kobbe, G.; Bornhauser, M.; Schwerdtfeger, R.; Baurmann, H.; Nagler, A.; Bethge, W.; Stelljes, M.; Uharek, L.; Wandt, H.; Burchert, A.; Corradini, P.; Schubert, J.; Kaufmann, Martin; Dreger, P.; Wulf, G.G.; Einsele, H.; Zabelina, T.; Kvasnicka, H.M.; Thiele, J.; Brand, R.; Zander, A.R.; Niederwieser, D.; Witte, T.J.M. de

    2009-01-01

    From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 m

  4. Climate Cycling on Early Mars Caused by the Carbonate-Silicate Cycle

    CERN Document Server

    Batalha, Natasha E; Haqq-Misra, Jacob; Kasting, James F

    2016-01-01

    For decades, scientists have tried to explain the evidence for fluvial activity on early Mars, but a consensus has yet to emerge regarding the mechanism for producing it. One hypothesis suggests early Mars was warmed by a thick greenhouse atmosphere. Another suggests that early Mars was generally cold but was warmed occasionally by impacts or by episodes of enhanced volcanism. These latter hypotheses struggle to produce the amounts of rainfall needed to form the martian valleys, but are consistent with inferred low rates of weathering compared to Earth. Here, we provide a geophysical mechanism that could have induced cycles of glaciation and deglaciation on early Mars. Our model produces dramatic climate cycles with extended periods of glaciation punctuated by warm periods lasting up to 10 Myr, much longer than those generated in other episodic warming models. The cycles occur because stellar insolation was low, and because CO2 outgassing is not able to keep pace with CO2 consumption by silicate weathering fo...

  5. Early Myocardial Dysfunction is Not Caused by Mitochondrial Abnormalities in a Rat Model of Peritonitis

    NARCIS (Netherlands)

    Smeding, Lonneke; van der Laarse, Willem J.; van Veelen, Toke A.; Lamberts, Regis R.; Niessen, Hans W. M.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan; Plotz, Frans B.

    2012-01-01

    Background. Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation

  6. QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease

    National Research Council Canada - National Science Library

    Guarani, Virginia; Jardel, Claude; Chrétien, Dominique; Lombès, Anne; Bénit, Paule; Labasse, Clémence; Lacène, Emmanuelle; Bourillon, Agnès; Imbard, Apolline; Benoist, Jean-François; Dorboz, Imen; Gilleron, Mylène; Goetzman, Eric S; Gaignard, Pauline; Slama, Abdelhamid; Elmaleh-Bergès, Monique; Romero, Norma B; Rustin, Pierre; Ogier de Baulny, Hélène; Paulo, Joao A; Harper, J Wade; Schiff, Manuel

    2016-01-01

    ... (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain...

  7. Myelofibrosis with myeloid metaplasia: disease overview and non-transplant treatment options.

    Science.gov (United States)

    Mesa, Ruben A; Barosi, Giovanni; Cervantes, Francisco; Reilly, John T; Tefferi, Ayalew

    2006-01-01

    Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To date, both the molecular basis of the primary clonal process and the pathogenetic mechanisms that underlie the secondary histological changes remain elusive. Clinically, MMM is characterized by anemia, multi-organ extramedullary hematopoiesis that often involves the spleen and liver, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Current diagnosis is based on characteristic but not diagnostic bone marrow histological features. Modern therapy remains palliative but allogeneic stem cell transplantation might be curative to a selected group of patients. This chapter reviews both the old and the new therapy with regard to non-transplant treatment options for MMM.

  8. Transcriptome analysis of bone marrow mesenchymal stromal cells from patients with primary myelofibrosis

    Directory of Open Access Journals (Sweden)

    Christophe Martinaud

    2015-09-01

    Full Text Available Primary myelofibrosis (PMF is a clonal myeloproliferative neoplasm whose severity and treatment complexity are attributed to the presence of bone marrow (BM fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironmental niches. Within these niches, mesenchymal stromal cells (BM-MSC play a hematopoietic supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic stem/progenitor cells. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic stem/progenitor cell deregulation that features PMF.

  9. Looking forward: novel therapeutic approaches in chronic and advanced phases of myelofibrosis.

    Science.gov (United States)

    Mascarenhas, John

    2015-01-01

    Myelofibrosis (MF) is complex at the pathobiologic level and heterogeneous at the clinical level. The advances in molecular characterization of MF provide important insight into the mechanisms driving this chronic myeloid malignancy, refine risk stratification, offer novel therapeutic targets, and serve to measure therapeutic response. Although JAK2 inhibition has been the focus of laboratory and clinical efforts over the last decade, current experimental therapeutic approaches have broadened to include inhibitors of key alternative signaling pathways, epigenetic modulators, anti-fibrotics, and immunotherapies. Based on compelling preclinical rationale, a number of JAK2 inhibitor based combination therapies are now actively being evaluated in the clinic with the goal of disease course modification. The role and timing of hematopoietic stem cell transplant (HSCT) for MF has been challenged with the availability of commercial ruxolitinib and the plethora of experimental treatment options that exist. Integration of preconditioning JAK2 inhibition, reduced intensity conditioning regimens, and alternative donor sources are all being explored in an attempt to optimize this potentially curative modality. This review will summarize modern MF risk stratification, current clinical research approaches to chronic and advance phase MF focusing on novel agents alone and in combination, and update the reader on new directions in HSCT.

  10. Cytokine Expression Pattern in Bone Marrow Microenvironment after Allogeneic Stem Cell Transplantation in Primary Myelofibrosis.

    Science.gov (United States)

    Hussein, Kais; Stucki-Koch, Angelika; Alchalby, Haefaa; Triviai, Ioanna; Kröger, Nicolaus; Kreipe, Hans

    2016-04-01

    The only curative therapy for primary myelofibrosis (PMF) is allogeneic stem cell transplantation (ASCT). However, although we know that patients can benefit from ASCT, we do not know the extent of the changes of the expression profile of cytokines and matrix modulation factors. In this first systematic analysis, we evaluated the expression profile of 103 factors before and after transplantation to identify potential biomarkers. The expression of fibrosis-, inflammation-, and angiogenesis-associated genes was analyzed in a total of 52 bone marrow biopsies: PMF patients (n = 14) before and after ASCT and, for control purposes, post-ASCT multiple myeloma patients (n = 14) and non-neoplastic hematopoiesis (n = 10). In post-ASCT PMF cases, decreased expression of tissue inhibitor of metalloproteinases (TIMP) and platelet-derived growth factor alpha (PDGFA) correlated with bone marrow remodeling and hematological remission. Expression of several other matrix factors remained at high levels and may contribute to post-ASCT remodeling. This is the first systematic analysis of cytokine expression in post-ASCT PMF bone marrow that shows that normalization of bone marrow microenvironment is paralleled by decreased expression of TIMP and PDGFA.

  11. Treatment and management of myelofibrosis in the era of JAK inhibitors.

    Science.gov (United States)

    Keohane, Clodagh; Radia, Deepti H; Harrison, Claire N

    2013-01-01

    Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.

  12. Clinical-Laboratory Significance of Myelofibrosis in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yuliya A. D'yachkova

    2014-06-01

    Full Text Available Background: Currently, there are not many studies of correlations between myelofibrosis (MF and clinical-laboratory data on multiple myeloma (MM. Methods and Results: In our study, MF was evaluated according to the scale of the European consensus (2005. Additionally, we used an automated morphometric study. The inverse correlations between the prevalence of MF and the total number of erythroid cells and megakaryocytes, as well as hemoglobin level were found. The total relative area of fibrosis tissue (Srel.fibr.tis. in initial and advanced MF>20% was associated with anemia requiring a blood transfusion.The development of severe anemia was observed in patients with a greater relative area of Srel.fibr.tis. The direct correlations between Srel.fibr.tis. and relative area of tumor tissue (Srel.tum.tis., between Srel.fibr.tis. and the level of total serum protein, between Srel.fibr.tis. and daily proteinuria were found both in initial and in advanced MF. Additionally, a direct correlation between Srel.fibr.tis. and the number of plasma cells was revealed in initial MF. Greater Srel.fibr.tis. in initial and advanced MF was found in patients with chronic renal failure. Conclusion: The clinical-laboratory significance of MF in MM is an inhibition of erythroid cells and megakaryocytes and development of anemia. The relative area of fibrous tissue is a marker of tumor volume and tumor progression.

  13. Portal hypertension secondary to myelofibrosis with myeloid metaplasia: A study of 13 cases

    Institute of Scientific and Technical Information of China (English)

    Mohannad Abu-Hilal; Jayant Tawaker

    2009-01-01

    AIM: To describe the clinical presentation and complications of portal hypertension (PH) secondary to myelofibrosis with myeloid metaplasia (MMM).METHODS: Medical records for 123 patients with MMM were reviewed.RESULTS: Thirteen patients with PH secondary to MMM were identified. Median ages at time of MMM and PH diagnosis were 61 and 66 years, respectively. The interval from MMM diagnosis to presentation with one of the PH features ranged from 1 to 11 years. Variceal bleeding and ascites were the most common presentations. Of the eight patients who presented with variceal bleeding, six patients underwent endoscopic variceal ligation (EVL) with no variceal recurrence or hematological worsening during a 12-mo follow up period.CONCLUSION: Patients with MMM might develop PH. Exact mechanisms leading to PH in MMM are still controversial. As in other etiologies, variceal bleeding and ascites are the most common presentations. Anemia may correlate with, and/or predict, the severity of the PH presentation in these patients. EVL can successfully control variceal bleeding in MMM. Further clinical studies are required.

  14. Behavioral and neural plasticity caused by early social experiences: the case of the honeybee

    Directory of Open Access Journals (Sweden)

    Andrés eArenas

    2013-08-01

    Full Text Available Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony as well. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe. Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees´ physiology, behavior and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits.

  15. Recovery in eastern Baltic cod: is increased recruitment caused by decreased predation on early life stages?

    DEFF Research Database (Denmark)

    Neumann, Viola; Köster, Fritz; Schaber, M.

    2014-01-01

    Cod (Gadus morhua) recruitment in the eastern Baltic Sea is influenced by predation on early life stages by sprat (Sprattus sprattus) and herring (Clupea harengus), which is considered as one of the mechanisms preventing cod recovery in the 1990s. In the light of improved cod recruitment in the s......Cod (Gadus morhua) recruitment in the eastern Baltic Sea is influenced by predation on early life stages by sprat (Sprattus sprattus) and herring (Clupea harengus), which is considered as one of the mechanisms preventing cod recovery in the 1990s. In the light of improved cod recruitment...

  16. Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

    Science.gov (United States)

    Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

    2017-02-01

    Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Postoperative medical complications are the main cause of early death after emergency surgery for colonic cancer

    DEFF Research Database (Denmark)

    Iversen, L.H.; Bulow, S.; Christensen, Ib Jarle

    2008-01-01

    . The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 percent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other...

  18. Neonatal dexamethasone administration causes progressive renal damage due to induction of an early inflammatory response

    NARCIS (Netherlands)

    Liu, Yan; van Goor, Harry; Havinga, Rick; Baller, Julius F. W.; Bloks, Vincent W.; van der Leij, Feike R.; Sauer, Pieter J. J.; Kuipers, Folkert; Navis, Gerjan; de Borst, Martin H.

    2008-01-01

    Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexa

  19. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized

  20. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia

  1. Early adiposity rebound: causes and consequences for obesity in children and adults.

    Science.gov (United States)

    Rolland-Cachera, M F; Deheeger, M; Maillot, M; Bellisle, F

    2006-12-01

    Childhood obesity is an important public health problem, with a rapidly increasing frequency worldwide. Identification of critical periods for the development of childhood and adolescent obesity could be very useful for targeting prevention measures. Weight status in early childhood is a poor predictor of adult adiposity status, and most obese adults were not obese as children. We first proposed to use the body mass index (BMI) charts to monitor individual BMI development. The adiposity rebound (AR) corresponds to the second rise in BMI curve that occurs between ages 5 and 7 years. It is not as direct a measure as BMI at any age, but because it involves the examination of several points during growth, and because it is identified at a time when adiposity level clearly change directions, this method provides information that can help us understand individual changes and the development of health risks. An early AR is associated with an increased risk of overweight. It is inversely associated with bone age, and reflects accelerated growth. The early AR recorded in most obese subjects and the striking difference in the mean age at AR between obese subjects (3 years) and non-obese subjects (6 years) suggest that factors have operated very early in life. The typical pattern associated with an early AR is a low BMI followed by increased BMI level after the rebound. This pattern is recorded in children of recent generations as compared to those of previous generations. This is owing to the trend of a steeper increase of height as compared to weight in the first years of life. This typical BMI pattern (low, followed by high body fatness level) is associated with metabolic diseases such as diabetes and coronary heart diseases. Low body fatness before the AR suggests that an energy deficit had occurred at an early stage of growth. It can be attributable to the high-protein, low-fat diet fed to infants at a time of high energy needs, the former triggering height velocity and

  2. Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

    Science.gov (United States)

    Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi

    2004-12-01

    A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

  3. Whole-blood transcriptional profiling of interferon-inducible genes identifies highly upregulated IFI27 in primary myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

    2011-01-01

    Gene expression profiling studies have unraveled deregulation of several genes that might be of pathogenetic importance for the development and phenotype of the Philadelphia-negative chronic myeloproliferative neoplasms. In the context of interferon-alpha2 as a promising therapeutic agent, we foc...... myelofibrosis as the burn-out phase of chronic inflammation which ultimately elicits clonal evolution and expansion owing to an exaggerated but incompetent antitumor immune response. Finally, IFI27 may be a novel biomarker of disease activity and tumor burden in patients with CMPNs....

  4. Autoimmune myelofibrosis accompanied by Sjögren's syndrome in a 47, XXX/46, XX mosaic woman.

    Science.gov (United States)

    Takahashi, Tohru

    2014-01-01

    This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.

  5. Whole Blood Transcriptional Profiling of Interferon-Inducible Genes Identifies Highly Upregulated IFI27 in Primary Myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

    2011-01-01

    Gene expression profiling studies have unraveled deregulation of several genes that might be of pathogenetic importance for the development and phenotype of the Philadelphia-negative chronic myeloproliferative neoplasms. In the context of interferon-alpha2 as a promising therapeutic agent, we foc...... myelofibrosis as the burn-out phase of chronic inflammation which ultimately elicits clonal evolution and expansion owing to an exaggerated but incompetent antitumor immune response. Finally, IFI27 may be a novel biomarker of disease activity and tumor burden in patients with CMPNs....

  6. [Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence].

    Science.gov (United States)

    Villalba, Gloria; Pacreu, Susana; Fernández-Candil, Juan Luis; León, Alba; Serrano, Laura; Conesa, Gerardo

    2016-01-01

    The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  7. Entorhinal cortex disruption causes memory deficit in early Alzheimer's disease as shown by PET.

    Science.gov (United States)

    Eustache, F; Desgranges, B; Giffard, B; de la Sayette, V; Baron, J C

    2001-03-26

    Voxel-based mapping of the correlations between cognitive scores and resting-state brain glucose utilization measured by PET has recently emerged as a novel way to reveal in living patients with Alzheimer's disease (AD) the neural systems whose disruption underlies particular neuropsychological, especially mnemonic, deficits. We have now applied this approach using a novel cognitive paradigm designed to selectively assess verbal episodic memory, and show that in early AD disruption of the left entorhinal cortex underlies this memory deficit, consistent with post mortem data showing that this brain area is affected earliest and most severely by tau pathology in AD.

  8. Tactile stimulation partially prevents neurodevelopmental changes in visual tract caused by early iron deficiency.

    Science.gov (United States)

    Horiquini-Barbosa, Everton; Gibb, Robbin; Kolb, Bryan; Bray, Douglas; Lachat, Joao-Jose

    2017-02-15

    Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. CRP at early follicular phase of menstrual cycle can cause misinterpretation for cardiovascular risk assessment.

    Science.gov (United States)

    Gursoy, Asli Yarci; Caglar, Gamze Sinem; Kiseli, Mine; Pabuccu, Emre; Candar, Tuba; Demirtas, Selda

    2015-12-01

    C-reactive protein (CRP) is a well-known marker of inflammation and infection in clinical practice. This study is designed to evaluate CRP levels in different phases of menstrual cycle, which might end up with misleading conclusions especially when used for cardiovascular risk assessment. Twenty-seven women were eligible for the cross-sectional study. Venous blood samples from each participant were collected twice during the menstrual cycle. The first sampling was held at 2nd to 5th days of the menstrual cycle for FSH, estradiol, CRP, and sedimentation, and the second was done at 21st to 24th days of the menstrual cycle for measurement of progesterone, CRP, and sedimentation values. CRP values were significantly higher in the early follicular phase compared to luteal phase (1.8 mg/L [0.3-7.67] vs. 0.7 mg/L [0.1-8.3], p menstrual cycle, sedimentation rate was similar (12.1 ± 6.7 vs. 12.3 ± 7.7; p = 0.717, respectively). CRP levels in early follicular phase of the menstrual cycle (menstruation) are significantly higher than CRP levels in luteal phase of the same cycle. In reproductive age women, detection of CRP for cardiovascular risk assessment during menstruation might not be appropriate.

  10. Iron Chelation Therapy with Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

    Science.gov (United States)

    Elli, Elena Maria; Belotti, Angelo; Aroldi, Andrea; Parma, Matteo; Pioltelli, Pietro; Pogliani, Enrico Maria

    2014-01-01

    Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required. PMID:24959339

  11. IRON CHELATION THERAPY WITH DEFERASIROX IN THE MANAGEMENT OF IRON OVERLOAD IN PRIMARY MYELOFIBROSIS

    Directory of Open Access Journals (Sweden)

    Elena Maria Elli

    2014-05-01

    Full Text Available Deferasirox (DSX is the principal option currently available for iron-chelation-therapy (ICT, principally in the management of myelodysplastic syndromes (MDS, while in primary myelofibrosis (PMF the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day, with 3 transient interruption of treatment for drug-related adverse events (AEs and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%, 2 of them (20% obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin were greater in hematologic responder (HR compared with non-responder (NR  patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP. Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP.  However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

  12. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis.

    Science.gov (United States)

    Rumi, Elisa; Pietra, Daniela; Pascutto, Cristiana; Guglielmelli, Paola; Martínez-Trillos, Alejandra; Casetti, Ilaria; Colomer, Dolors; Pieri, Lisa; Pratcorona, Marta; Rotunno, Giada; Sant'Antonio, Emanuela; Bellini, Marta; Cavalloni, Chiara; Mannarelli, Carmela; Milanesi, Chiara; Boveri, Emanuela; Ferretti, Virginia; Astori, Cesare; Rosti, Vittorio; Cervantes, Francisco; Barosi, Giovanni; Vannucchi, Alessandro M; Cazzola, Mario

    2014-08-14

    We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials. © 2014 by The American Society of Hematology.

  13. Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis

    Science.gov (United States)

    Campanelli, Rita; Fois, Gabriela; Catarsi, Paolo; Poletto, Valentina; Villani, Laura; Erba, Benedetta Gaia; Maddaluno, Luigi; Jemos, Basilio; Salmoiraghi, Silvia; Guglielmelli, Paola; Abbonante, Vittorio; Di Buduo, Christian Andrea; Balduini, Alessandra; Iurlo, Alessandra; Barosi, Giovanni; Rosti, Vittorio; Massa, Margherita

    2016-01-01

    Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph−) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62−CCR2− (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ. PMID:27281335

  14. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis.

    Science.gov (United States)

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol

    2014-06-10

    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

  15. Menkes disease – An important cause of early onset refractory seizures

    Directory of Open Access Journals (Sweden)

    Puneet Jain

    2014-01-01

    Full Text Available Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4, myoclonic (2 and tonic seizures (1. The electroencephalographic abnormalities included hypsarrythmia (2 and multifocal epileptiform discharges (3. The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis.

  16. Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

    Science.gov (United States)

    Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

    2015-01-01

    Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

  17. Myelofibrotic transformations of polycythemia vera and essential thrombocythemia are morphologically, biologically, and prognostically indistinguishable from primary myelofibrosis.

    Science.gov (United States)

    Sangle, Nikhil; Cook, Josh; Perkins, Sherrie; Teman, Carolin J; Bahler, David; Hickman, Kimberly; Wilson, Andrew; Prchal, Josef; Salama, Mohamed E

    2014-10-01

    A fraction of polycythemia vera (PV) and essential thrombocythemia (ET) cases will, in time, undergo myelofibrotic transformation. In such cases, fibrosis may mask the diagnostic histologic features of the original underlying myeloproliferative neoplasm. Thus, confidently differentiating postfibrotic PV/ET from primary myelofibrosis (PMF) histologically may not be possible. It is controversial whether post-PV/ET myelofibrosis (MF) differs clinicopathologically from PMF, or whether these entities are biologically, clinically, and prognostically indistinguishable. To answer this question, we compared multiple candidate biological, morphologic, and prognostic parameters between 19 postfibrotic ET/PV individuals and 18 PMF individuals. The postfibrotic ET/PV and PMF cases did not differ with regard to clinical outcome, cytogenetic abnormalities, serum lactate dehydrogenase level, peripheral blast count, bone marrow morphology, or grade of reticulin fibrosis. Only JAK2 allele burden, which was higher in the postfibrotic PV/ET population (P=0.011), differed between the 2 groups. Cardinal morphologic features of PMF (ie, marrow cellularity, intrasinusoidal hematopoiesis, osteosclerosis, etc.) were commonly observed in post-PV/ET MF marrow biopsies, and only a minority of post-PV/ET MF marrow biopsies the retained diagnostic features of the primary myeloproliferative neoplasm (panmyelosis in PV and megakaryocytic hyperplasia in ET). Our study indicates that PMF and post-PV/ET MF are clinically and biologically indistinguishable.

  18. Assessment of bone marrow inflammation in patients with myelofibrosis: an {sup 18}F-fluorodeoxyglucose PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Alchalby, Haefaa; Triviai, Ioanna; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany); Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany)

    2015-04-01

    Myelofibrosis is a haematopoietic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary haematopoiesis. The aim of this study was to determine if {sup 18}F-FDG PET/CT can be used to noninvasively visualize and quantify the extent and activity of bone marrow involvement. In 30 patients, the biodistribution of {sup 18}F-FDG was analysed by measuring the standardized uptake value in the bone marrow compartment and spleen. Imaging findings were compared with laboratory, cytogenetic and histopathological data. Retention of {sup 18}F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, ranging from mildly increased uptake in the central skeleton to extensive uptake in most parts of the skeleton. The extent of bone marrow involvement decreased over time from initial diagnosis (r{sub s} = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (r{sub s} = -0.37, p = 0.04). There was a significant positive correlation between the metabolic activity of the bone marrow and that of the spleen (p = 0.04). {sup 18}F-FDG PET/CT is as a promising technique for the quantitation of bone marrow inflammation in myelofibrosis. Our data indicate that the intensity of bone marrow {sup 18}F-FDG uptake decreases as bone marrow fibrosis increases. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET. (orig.)

  19. The self-incompatibility response in Papaver rhoeas pollen causes early and striking alterations to organelles.

    Science.gov (United States)

    Geitmann, A; Franklin-Tong, V E; Emons, A C

    2004-08-01

    Self-incompatibility (SI) in Papaver rhoeas is accompanied by a cascade of signalling events that result in the rapid arrest and eventual death of the pollen tube. We have used rapid freeze fixation, freeze substitution and transmission electron microscopy to provide the first description of changes to pollen at the ultrastructural level during SI in this species. Our studies reveal that dramatic alterations to the morphology of mitochondria, Golgi bodies and ER occur within 1 h of SI induction. Similar symptoms have also been observed during programmed cell death (PCD) in some cell types. These include: the conspicuous condensation of the vegetative and generative nuclei, the swelling and loss of cristae in mitochondria and the disappearance of Golgi bodies. Some of the early alterations to the mitochondria and Golgi bodies observed at 1 h, almost certainly occur when cells are still alive. Other events, such as nuclear condensation, occur later and coincide with DNA fragmentation and the loss of cell viability. Our observations suggest that the SI response in P. rhoeas pollen may potentially involve a type of PCD.

  20. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.

    Science.gov (United States)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velde, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2017-01-05

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null. Metabolomics analyses demonstrated a significant concomitant accumulation of the MDH substrate, malate, and fumarate, its immediate precursor in the Krebs cycle, in affected subjects' fibroblasts. Lentiviral complementation with wild-type MDH2 cDNA restored MDH2 levels and mitochondrial MDH activity. Additionally, introduction of the three missense mutations from the affected subjects into Saccharomyces cerevisiae provided functional evidence to support their pathogenicity. Disruption of the Krebs cycle is a hallmark of cancer, and MDH2 has been recently identified as a novel pheochromocytoma and paraganglioma susceptibility gene. We show that loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children.

  1. Systemic thioridazine in combination with dicloxacillin against early aortic graft infections caused by Staphylococcus aureus in a porcine model

    DEFF Research Database (Denmark)

    Stenger, Michael; Behr-Rasmussen, Carsten; Klein, Kasper

    2017-01-01

    the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model. METHODS: The synergism of DCX+TDZ against MSSA was initially assessed in vitro...... by viability assay. Thereafter, thirty-two pigs had polyester grafts implanted in the infrarenal aorta, followed by inoculation with 106 CFU of MSSA, and were randomly administered oral systemic treatment with either 1) DCX or 2) DCX+TDZ. Treatment was initiated one week postoperatively and continued...

  2. [Gallstone ileus as a cause of acute abdomen. Importance of early diagnosis for surgical treatment].

    Science.gov (United States)

    Martín-Pérez, Jesica; Delgado-Plasencia, Luciano; Bravo-Gutiérrez, Alberto; Burillo-Putze, Guillermo; Martínez-Riera, Antonio; Alarcó-Hernández, Antonio; Medina-Arana y, Vicente

    2013-10-01

    Gallstone ileus is an uncommon type of mechanical intestinal obstruction caused by an intraluminal gallstone, and preoperative diagnosis is difficult in the Emergency department. This study is a retrospective analysis of the clinical presentation of 5 patients with gallstone ileus treated between 2000-2010. Clinical features, diagnostic testing, and surgical treatment were analyzed. Five patients were included: 2 cases showed bowel obstruction; 2 patients presented a recurrent gallstone ileus with prior surgical intervention; and one patient presented acute peritonitis due to perforation of an ileal diverticula. In all cases CT confirmed the preoperative diagnosis. In our experience, gallstone ileus may present with clinical features other than intestinal obstruction. In suspicious cases CT may be useful to decrease diagnostic delay, which is associated with more complications.

  3. Mutations in MODY Genes Are not Common Cause of Early-Onset Type 2 Diabetes in Mexican Families

    Directory of Open Access Journals (Sweden)

    Bravo-Ríos LE

    2005-05-01

    Full Text Available CONTEXT: Maturity-onset diabetes of the young (MODY is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

  4. EVALUATION OF DISEASE RESISTANCE POTENTIAL OF SEVEN POTATO GENOTYPES AGAINST EARLY BLIGHT CAUSED BY Alternaria tenuissima UNDER GREENHOUSE CONDITIONS

    Directory of Open Access Journals (Sweden)

    Hamid Reza Mirkarimi

    2013-07-01

    Full Text Available Early blight of potato was caused by various species of genus Alternaria, the disease has a prominent role in reducing crop yields in most of the countries, especially in Iran. Various studies has been conducted for the finding out the information regarding the diversity of pathogen and estimation of damage caused by genus Alternaria tenuissima in Iran, but the information regarding the resistance against this fungal pathogen in various genotype of potatoes are in scarcity. Seven isolates of potato were obtained from the National Plant Gene Bank of Iran. Amongst these seven, on the basis of mean comparison curve progress Cosmos was recognized as the most sensitive genetic samples while the samples Armida was reported as a most resistant to the disease. Other cultivars showed different levels of resistance against this pathogen.

  5. Early signals of environmental and health impacts caused by uranium mining in Caetite, Bahia, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Brito, Adelson S. de; Rego, Rita de Cassia Franco [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Dept. de Medicina Preventiva. Programa de Pos-Graduacao em Saude, Ambiente e Trabalho; Zucchi, Maria do Rosario [Universidade Federal da Bahia (UFBA), Salvador, BA (Brazil). Dept. de Fisica da Terra. Lab. de Fisica Nuclear Aplicada; Navarro, Marcus V. Teixeira, E-mail: mvtn@ifba.edu.b [Instituto Federal da Bahia (LAFIR/NTS/IFBA) Salvador, BA (Brazil). Nucleo de Tecnologia em Saude. Lab. de Fisica Radiologica

    2011-07-01

    Uranium mining and processing at Lagoa Real (Bahia, Brazil) in the southwest of Bahia state started in the year 2000.The processing of uranium ore for obtaining U3O8 (yellowcake) is done today in the processing unit of the Brazilian Nuclear Industries INB located in the area of the same municipality above mentioned. The production capacity is 400 tons / year of U3O8, and the reserves in this region are estimated at 100.000 tons of uranium without any other associated minerals, enough to supply the demand for nuclear power plants Angra I and II for over 100 years. Since the granting of AOP (Permanent Operation Authorization) by CNEN (National Commission on Nuclear Energy) in the year 2009, there were some incidents at the facility, such as: solvents and liquid containing uranium overflow; pipes rupture, causing indiscriminate dispersion of toxic acids and other chemical agents; collapse of parts of the slope of the open pit. CNEN admitted in an official press release on April 1, 2011 that 'INB has no capacity to produce annual reports on environmental monitoring (unable to perform radiometric measurements, etc.). The last time a report was released happened in the year 2008. These reports are vital to the environmental impact assessment of the facility'. Another potential source of environmental and health negative impacts on the local population could be linked to radon emission. What are the levels of this important pollutant in the affected areas? (author)

  6. Sensory deprivation during early development causes an increased exploratory behavior in a whisker-dependent decision task.

    Science.gov (United States)

    Papaioannou, Stylianos; Brigham, Leeann; Krieger, Patrik

    2013-01-01

    Stimulation of sensory pathways is important for the normal development of cortical sensory areas, and impairments in the normal development can have long-lasting effect on animal's behavior. In particular, disturbances that occur early in development can cause permanent changes in brain structure and function. The behavioral effect of early sensory deprivation was studied in the mouse whisker system using a protocol to induce a 1-week sensory deprivation immediately after birth. Only two rows of whiskers were spared (C and D rows), and the rest were deprived, to create a situation where an unbalanced sensory input, rather than a complete loss of input, causes a reorganization of the sensory map. Sensory deprivation increased the barrel size ratio of the spared CD rows compared with the deprived AB rows; thus, the map reorganization is likely due, at least in part, to a rewiring of thalamocortical projections. The behavioral effect of such a map reorganization was investigated in the gap-crossing task, where the animals used a whisker that was spared during the sensory deprivation. Animals that had been sensory deprived performed equally well with the control animals in the gap-crossing task, but were more active in exploring the gap area and consequently made more approaches to the gap - approaches that on average were of shorter duration. A restricted sensory deprivation of only some whiskers, although it does not seem to affect the overall performance of the animals, does have an effect on their behavioral strategy on executing the gap-crossing task.

  7. Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex.

    Science.gov (United States)

    Poort, Jasper; Self, Matthew W; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R

    2016-10-01

    Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure-ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both.We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression.We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current-source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure-ground organization.

  8. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

    Directory of Open Access Journals (Sweden)

    Yana Pikman

    2006-07-01

    Full Text Available BACKGROUND: The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV, essential thrombocytosis (ET, and myelofibrosis with myeloid metaplasia (MF. Subsequent analysis has shown that constitutive activation of the JAK-STAT signal transduction pathway is an important pathogenetic event in these patients, and that enzymatic inhibition of JAK2V617F may be of therapeutic benefit in this context. However, a significant proportion of patients with ET or MF are JAK2V617F-negative. We hypothesized that activation of the JAK-STAT pathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR, the thrombopoietin receptor (MPL, or the granulocyte-colony stimulating factor receptor (GCSFR. METHODS AND FINDINGS: DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L in 9% (4/45 of JAKV617F-negative MF. Expression of MPLW515L in 32D, UT7, or Ba/F3 cells conferred cytokine-independent growth and thrombopoietin hypersensitivity, and resulted in constitutive phosphorylation of JAK2, STAT3, STAT5, AKT, and ERK. Furthermore, a small molecule JAK kinase inhibitor inhibited MPLW515L-mediated proliferation and JAK-STAT signaling in vitro. In a murine bone marrow transplant assay, expression of MPLW515L, but not wild-type MPL, resulted in a fully penetrant myeloproliferative disorder characterized by marked thrombocytosis (Plt count 1.9-4.0 x 10(12/L, marked splenomegaly due to extramedullary hematopoiesis, and increased reticulin fibrosis. CONCLUSIONS: Activation of JAK-STAT signaling via MPLW515L is an important pathogenetic event in patients with JAK2V617F-negative MF. The bone marrow transplant model of MPLW515L

  9. Readmission Rate and Causes at 90-Day after Radical Cystectomy in Patients on Early Recovery after Surgery Protocol

    Science.gov (United States)

    Altobelli, Emanuela; Buscarini, Maurizio; Gill, Harcharan S.; Skinner, Eila C.

    2017-01-01

    Background: Radical cystectomy (RC) is associated with high risk of early and late perioperative complications, and readmissions. The Enhanced Recovery After Surgery (ERAS) protocol has been applied to RC showing decreased hospital stay without increased morbidity. Objective: To evaluate the specific causes of hospital readmissions in RC patients treated before and after adoption of an ERAS protocol at our institution. Methods: We retrospectively evaluated the outcome of 207 RC patients on ERAS protocol at the Stanford University Hospital from January 2012 to December 2014. We focused on early (30-day) and late (90-day) postoperative readmission rate and causes. Results were compared with a pre-ERAS consecutive series of 177 RC patients from January 2009 to December 2011. Results: In the post-ERAS time period a total of 56 patients were readmitted, 41 within the first 30 days after surgery (20%) and 15 within the following 60 days (7%). Fever, often associated with dehydration, was the most common reason for presentation to the hospital, accounting for 57% of all readmissions. At 90 days infection accounted for 53% of readmissions. Of all the patients readmitted during the first 90 days after surgery, 32 had positive urine cultures, mostly caused by Enterococcus faecalis isolated in 18 (56%). Readmission rates did not increase since the introduction of the ERAS protocol, with an incidence of 27% in the post-ERAS group versus 30% in the pre-ERAS group. Conclusions: Despite accurate adherence to most recent perioperative antibiotic guidelines, the incidence of readmissions after RC due to infection still remains significant. PMID:28149935

  10. Assessing Bone Marrow Activity in Patients with Myelofibrosis: Results of a Pilot Study of (18)F-FLT PET.

    Science.gov (United States)

    Vercellino, Laetitia; Ouvrier, Matthieu John; Barré, Emmanuelle; Cassinat, Bruno; de Beco, Virginie; Dosquet, Christine; Chevret, Sylvie; Meignin, Véronique; Chomienne, Christine; Toubert, Marie-Elisabeth; Merlet, Pascal; Kiladjian, Jean-Jacques

    2017-10-01

    An emerging noninvasive approach to assess tissue proliferation uses the PET tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT). To evaluate the diagnostic value of this technique in myelofibrosis, (18)F-FLT PET imaging results were compared with bone marrow histology and bone marrow scintigraphy (BMS), the gold standard techniques in this clinical situation. Methods: Fifteen patients with histology-proven myelofibrosis were included consecutively in the study. Tracers' distributions were assessed using a visual grading assessment score of the uptake in the axial skeleton, proximal and distal limbs, liver, and spleen. This visual score was used to define patterns of tracer distribution and to compare the information provided either by PET or by BMS. A semiquantitative analysis with determination of SUVmax in the same localizations was performed for (18)F-FLT PET. Results: The histology grade of fibrosis correlated with the SUVmax in the axial skeleton (spine and iliac crests) and proximal limbs. (18)F-FLT uptake in these areas was much lower in patients with grade 3 fibrosis than in patients with grade 1 or 2 fibrosis. (18)F-FLT PET showed the same distribution of uptake as BMS in 13 of 14 patients (1 patient did not undergo BMS). In 1 patient, (18)F-FLT PET clearly showed an intense abnormal splenic uptake, whereas spleen uptake was inconclusive with BMS. Conclusion:(18)F-FLT PET appears to be a reliable and convenient technique to assess hematopoietic activity in bone marrow. It yields results close to those observed with BMS. In our study population, (18)F-FLT uptake in the axial skeleton and proximal limbs assessed by SUVmax correlated with the grade of fibrosis. Thus, (18)F-FLT PET may be a useful tool to measure the severity of myelofibrosis, and to monitor noninvasively the patients' status during follow-up. Finally, (18)F-FLT PET may be foreseen as an alternative to BMS. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  11. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  12. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    Science.gov (United States)

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val.

  13. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

    Science.gov (United States)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB-mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.

  14. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early onset autoinflammatory syndrome

    Science.gov (United States)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M.; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J.; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T.; Zaal, Kristien; Chandrasekharappa, Settara C.; Hanson, Eric P.; Yu, Zhen; Mullikin, James C.; Hasni, Sarfaraz A.; Wertz, Ingrid; Ombrello, Amanda K.; Stone, Deborah L.; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K.; Leavis, Helen L.; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D.; Gül, Ahmet; Siegel, Richard M.; Boehm, Manfred; Milner, Joshua D.; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M.; Kastner, Daniel L.; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity1. Herein we describe a new syndrome caused by high penetrance heterozygous germline mutations in the NFκB regulatory protein TNFAIP3 (A20) in six unrelated families with early onset systemic inflammation. The syndrome resembles Behçet’s disease (BD), which is typically considered a polygenic disorder with onset in early adulthood2. A20 is a potent inhibitor of the NFκB signaling pathway3. TNFAIP3 mutant truncated proteins are likely to act by haploinsufficiency since they do not exert a dominant-negative effect in overexpression experiments. Patients’ cells show increased degradation of IκBα and nuclear translocation of NFκB p65, and increased expression of NFκB-mediated proinflammatory cytokines. A20 restricts NFκB signals via deubiquitinating (DUB) activity. In cells expressing the mutant A20 protein, there is defective removal of K63-linked ubiquitin from TRAF6, NEMO, and RIP1 after TNF stimulation. NFκB-dependent pro-inflammatory cytokines are potential therapeutic targets for these patients. PMID:26642243

  15. Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Toshihiko Toda

    2011-01-01

    Full Text Available In order to clarify the pathophysiological role of presenilin-2 (PS2 carrying the Volga German Kindred mutation (N141I in a conventional mouse model of Alzheimer's disease (AD expressing amyloid precursor protein (APP with the Swedish mutation (Tg2576 line, we generated a double transgenic mouse (PS2Tg2576 by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies.

  16. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis.

    Science.gov (United States)

    Rumi, Elisa; Harutyunyan, Ashot S; Pietra, Daniela; Milosevic, Jelena D; Casetti, Ilaria C; Bellini, Marta; Them, Nicole C C; Cavalloni, Chiara; Ferretti, Virginia V; Milanesi, Chiara; Berg, Tiina; Sant'Antonio, Emanuela; Boveri, Emanuela; Pascutto, Cristiana; Astori, Cesare; Kralovics, Robert; Cazzola, Mario

    2014-04-10

    Somatic mutations in the calreticulin (CALR) gene were recently discovered in patients with sporadic essential thrombocythemia (ET) and primary myelofibrosis (PMF) lacking JAK2 and MPL mutations. We studied CALR mutation status in familial cases of myeloproliferative neoplasm. In a cohort of 127 patients, CALR indels were identified in 6 of 55 (11%) subjects with ET and in 6 of 20 (30%) with PMF, whereas 52 cases of polycythemia vera had nonmutated CALR. All CALR mutations were somatic, found in granulocytes but not in T lymphocytes. Patients with CALR-mutated ET showed a higher platelet count (P = .017) and a lower cumulative incidence of thrombosis (P = .036) and of disease progression (P = .047) compared with those with JAK2 (V617F). In conclusion, a significant proportion of familial ET and PMF nonmutated for JAK2 carry a somatic mutation of CALR.

  17. Disruption of the ASXL1 gene is frequent in primary, post-essential thrombocytosis and post-polycythemia vera myelofibrosis, but not essential thrombocytosis or polycythemia vera: analysis of molecular genetics and clinical phenotypes

    Science.gov (United States)

    Stein, Brady L.; Williams, Donna M.; O’Keefe, Christine; Rogers, Ophelia; Ingersoll, Roxann G.; Spivak, Jerry L.; Verma, Amit; Maciejewski, Jarek P.; McDevitt, Michael A.; Moliterno, Alison R.

    2011-01-01

    Background The myeloproliferative neoplasms, essential thrombocytosis, polycythemia vera and primary myelofibrosis, share the same acquired genetic lesion, but the concept of JAK2 V617F serving as the sole lesion responsible for these neoplasms is under question, and there has been interest in identifying additional mutations that may contribute to disease pathogenesis. Because ASXL1 lesions have been increasingly identified in myeloid neoplasms, we examined the relationships of ASXL1 mutation or deletion to both clinical phenotype and associated molecular features in 166 patients with myeloproliferative neoplasms. Design and Methods Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia. Pyrosequencing assays were designed to determine the allele percentages of JAK2 V617F (G5073770T), ASXL1 2475dupA, and ASXL1 2846_2847del in neutrophil genomic DNA samples. Clinical and laboratory characteristics of patients with wild-type and ASXL1 mutations were then compared. Results We identified nonsense mutations or hemizygous deletion of ASXL1 in 36% of the patients with myelofibrosis, but very rarely among those with polycythemia vera or essential thrombocytosis. Among the patients with myelofibrosis, those with ASXL1 lesions were not distinguished from their wild-type counterparts with regard to JAK2 V617F status, exposure to chemotherapy or evolution to leukemia. Myelofibrosis patients with ASXL1 lesions were more likely to have received anemia-directed therapy compared to those without lesions [15/26 (58%) versus 11/39 (23%); P=0.02]. Using serial banked samples and quantitative ASXL1 mutant allele burden assays, we observed the acquisition and accumulation of ASXL1 mutations over

  18. Disruption of the ASXL1 gene is frequent in primary, post-essential thrombocytosis and post-polycythemia vera myelofibrosis, but not essential thrombocytosis or polycythemia vera: analysis of molecular genetics and clinical phenotypes.

    Science.gov (United States)

    Stein, Brady L; Williams, Donna M; O'Keefe, Christine; Rogers, Ophelia; Ingersoll, Roxann G; Spivak, Jerry L; Verma, Amit; Maciejewski, Jarek P; McDevitt, Michael A; Moliterno, Alison R

    2011-10-01

    The myeloproliferative neoplasms, essential thrombocytosis, polycythemia vera and primary myelofibrosis, share the same acquired genetic lesion, but the concept of JAK2 V617F serving as the sole lesion responsible for these neoplasms is under question, and there has been interest in identifying additional mutations that may contribute to disease pathogenesis. Because ASXL1 lesions have been increasingly identified in myeloid neoplasms, we examined the relationships of ASXL1 mutation or deletion to both clinical phenotype and associated molecular features in 166 patients with myeloproliferative neoplasms. Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia. Pyrosequencing assays were designed to determine the allele percentages of JAK2 V617F (G5073770T), ASXL1 2475dupA, and ASXL1 2846_2847del in neutrophil genomic DNA samples. Clinical and laboratory characteristics of patients with wild-type and ASXL1 mutations were then compared. We identified nonsense mutations or hemizygous deletion of ASXL1 in 36% of the patients with myelofibrosis, but very rarely among those with polycythemia vera or essential thrombocytosis. Among the patients with myelofibrosis, those with ASXL1 lesions were not distinguished from their wild-type counterparts with regard to JAK2 V617F status, exposure to chemotherapy or evolution to leukemia. Myelofibrosis patients with ASXL1 lesions were more likely to have received anemia-directed therapy compared to those without lesions [15/26 (58%) versus 11/39 (23%); P=0.02]. Using serial banked samples and quantitative ASXL1 mutant allele burden assays, we observed the acquisition and accumulation of ASXL1 mutations over time in two patients with post

  19. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    Energy Technology Data Exchange (ETDEWEB)

    Leu, Yu-Wei [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Chu, Pei-Yi [Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China); Chen, Chien-Min [Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China); Yeh, Kun-Tu [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Hsiao, Shu-Huei, E-mail: bioshh@ccu.edu.tw [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)

    2014-10-24

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

  20. Ectopic expression of Jatropha curcas APETALA1 (JcAP1 caused early flowering in Arabidopsis, but not in Jatropha

    Directory of Open Access Journals (Sweden)

    Mingyong Tang

    2016-04-01

    Full Text Available Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1 is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1 was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha.

  1. Early involvement of lysosome dysfunction in the degeneration of cerebral cortical neurons caused by the lipid peroxidation product 4-hydroxynonenal.

    Science.gov (United States)

    Zhang, Shi; Eitan, Erez; Mattson, Mark P

    2017-03-01

    Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy-lysosome pathway in rat primary cortical neurons. We found that HNE, at a concentration that causes apoptosis over a 48-72 h period, increases protein levels of LC3 II and p62 and within 1 and 4 h of exposure, respectively; LC3 II and p62 immunoreactive puncta were observed in the cytoplasm of HNE-treated neurons at 6 h. The extent of up-regulation of p62 and LC3 II in response to HNE was not affected by co-treatment with the lysosome inhibitor bafilomycin A1, suggesting that the effects of HNE on autophagy were secondary to lysosome inhibition. Indeed, we found that neurons exposed to HNE exhibit elevated pH levels, and decreased protein substrate hydrolysis and cathepsin B activity. Neurons exposed to HNE also exhibited the accumulation of K63-linked polyubiquitinated proteins, which are substrates targeted for lysosomal degradation. Moreover, we found that the levels of LAMP2a and constitutively active heat-shock protein 70, and numbers of LAMP2a-positive lysosomes, are decreased in neurons exposed to HNE. Our findings demonstrate that the lipid peroxidation product HNE causes early impairment of lysosomes which may contribute to the accumulation of damaged and dysfunctional proteins and organelles and consequent neuronal death. Because impaired lysosome function is increasingly recognized as an early event in the neuronal death that occurs in neurodegenerative

  2. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  3. Early changes of volume and spatial location in target and normal tissues caused by IMRT for cervical cancer.

    Science.gov (United States)

    Chen, Jianwu; Liu, Ping; Chen, Wenjuan; Bai, Penggang; Li, Jiangshan; Ni, Xiaolei; Chen, Kaiqiang; Li, Qixin

    2016-12-01

    To investigate the early changes of volume and spatial location in target and normal tissues caused by intensity-modulated radiotherapy (IMRT) for cervical cancer. Forty patients with cervical cancer were included in this study and treated by IMRT. Computed tomography (CT) was performed before radiotherapy and when the patient had received 27 Gy in 15 fractions. After image registration, the volume of interest (VOI) for the targets and organs at risk was delineated by clinicians on the CT images. Changes of volume, spatial location and Dice similarity were calculated for all VOIs. There were significant changes in gross tumor volume (GTV) in the primary tumor (GTV-T) with t = 8.304 (p<0.01) and visible pelvic lymph nodes (GTV-N) with t = 4.996 (p<0.01) caused by IMRT. The mean volume differences for GTV-T and GTV-N were 38.64% ± 19.50% (range 3.16%-86.49%) and 42.49% ± 25.68% (range 2.79%-87.42%), respectively. Among the organs at risk, the bladder had the greatest volume change with 55.13% ± 33.40% (range 3.25%-116.01%). The Dice similarity for GTV-T and GTV-N was 0.50 ± 0.18 (range 0.10-0.85) and 0.31 ± 0.20 (range 0.00-0.71), respectively. The rectum had the least Dice similarity among the normal tissues, with a mean value of 0.57 ± 0.14 (range 0.18-0.76). There were significant changes in volume and spatial location of the target and normal tissues after 27 Gy IMRT. In order to maintain the radiation dose to the targets and minimize the radiation to normal tissues, it is necessary to modify the radiotherapy planning.

  4. Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

    Science.gov (United States)

    Henry-Amar, M; Hayat, M; Meerwaldt, J H; Burgers, M; Carde, P; Somers, R; Noordijk, E M; Monconduit, M; Thomas, J; Cosset, J M

    1990-11-01

    The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

  5. The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy.

    Science.gov (United States)

    Stepensky, Polina; Saada, Ann; Cowan, Marianne; Tabib, Adi; Fischer, Ute; Berkun, Yackov; Saleh, Hani; Simanovsky, Natalia; Kogot-Levin, Aviram; Weintraub, Michael; Ganaiem, Hamam; Shaag, Avraham; Zenvirt, Shamir; Borkhardt, Arndt; Elpeleg, Orly; Bryant, Nia J; Mevorach, Dror

    2013-06-20

    Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in the VPS45 gene in infants from consanguineous families who suffered from life-threatening neutropenia, which was refractory to granulocyte CSF, from defective platelet aggregation and myelofibrosis. The mutation segregated in the families, was not present in controls, affected a highly conserved codon, and apparently destabilized the Vps45 protein, which was reduced in the patients' leukocytes. Introduction of the corresponding mutation into yeast resulted in reduced cellular levels of Vps45 and also of the cognate syntaxin Tlg2, which is required for membrane traffic through the endosomal system. A defect in the endosomal-lysosomal pathway, the homologous system in humans, was suggested by the absence of lysosomes in the patients' fibroblasts and by the depletion of α granules in their platelets. Importantly, accelerated apoptosis was observed in the patients' neutrophils and bone marrow. This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure.

  6. VPS 45-associated primary infantile myelofibrosis--successful treatment with hematopoietic stem cell transplantation.

    Science.gov (United States)

    Stepensky, Polina; Simanovsky, Natalia; Averbuch, Diana; Gross, Menachem; Yanir, Asaf; Mevorach, Dror; Elpeleg, Orly; Weintraub, Michael

    2013-12-01

    PMF of infancy is a recently described autosomal recessive disorder presenting with severe bone marrow failure, accelerated neutrophil apoptosis, and significant platelet dysfunction, caused by a mutation in the VPS45 gene. In this study, we update our group of patients with PMF, highlighting different aspects of this disease, and evaluating the effectiveness of HSCT for the treatment of this disorder. Update of clinical data, hematological features, molecular studies, treatment and final outcome of four children diagnosed with VPS 45-associated PMF of infancy. The patients described had clinical and hematological findings consistent with MF. Molecular studies showed that all patients were homozygous for the Thr224Asn mutation in the VPS 45 gene. HSCT was carried out in three patients and was successful in two. VPS 45-associated MF is a novel primary immune deficiency that can be successfully corrected by HSCT if applied early in the course of disease using appropriate conditioning. The diagnosis of VPS 45-associated PMF should be considered in all children presenting with SCN with subsequent development of pancytopenia. Long-term follow-up of these patients is necessary to identify extra-hematological manifestations of VPS45 deficiency. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Christensen, J H; Kvistgaard, H; Knudsen, J; Shaikh, G; Tolmie, J; Cooke, S; Pedersen, S; Corydon, T J; Gregersen, N; Rittig, S

    2013-01-01

    Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.

  8. Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause Sustained Impairments in Attention and Academic Functioning?

    Science.gov (United States)

    Pardini, Dustin; White, Helene R; Xiong, Shuangyan; Bechtold, Jordan; Chung, Tammy; Loeber, Rolf; Hipwell, Alison

    2015-10-01

    There is some suggestion that heavy marijuana use during early adolescence (prior to age 17) may cause significant impairments in attention and academic functioning that remain despite sustained periods of abstinence. However, no longitudinal studies have examined whether both male and female adolescents who engage in low (less than once a month) to moderate (at least once a monthly) marijuana use experience increased problems with attention and academic performance, and whether these problems remain following sustained abstinence. The current study used within-individual change models to control for all potential pre-existing and time-stable confounds when examining this potential causal association in two gender-specific longitudinal samples assessed annually from ages 11 to 16 (Pittsburgh Youth Study N = 479; Pittsburgh Girls Study N = 2296). Analyses also controlled for the potential influence of several pertinent time-varying factors (e.g., other substance use, peer delinquency). Prior to controlling for time-varying confounds, analyses indicated that adolescents tended to experience an increase in parent-reported attention and academic problems, relative to their pre-onset levels, during years when they used marijuana. After controlling for several time-varying confounds, only the association between marijuana use and attention problems in the sample of girls remained statistically significant. There was no evidence indicating that adolescents who used marijuana experienced lingering attention and academic problems, relative to their pre-onset levels, after abstaining from use for at least a year. These results suggest that adolescents who engage in low to moderate marijuana use experience an increase in observable attention and academic problems, but these problems appear to be minimal and are eliminated following sustained abstinence.

  9. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos‐like syndrome

    Science.gov (United States)

    Uzumcu, A; Norgett, E E; Dindar, A; Uyguner, O; Nisli, K; Kayserili, H; Sahin, S E; Dupont, E; Severs, N J; Leigh, I M; Yuksel‐Apak, M; Kelsell, D P; Wollnik, B

    2006-01-01

    Background Desmosomes are cellular junctions important for intercellular adhesion and anchoring the intermediate filament (IF) cytoskeleton to the cell membrane. Desmoplakin (DSP) is the most abundant desmosomal protein with 2 isoforms produced by alternative splicing. Methods We describe a patient with a recessively inherited arrhythmogenic dilated cardiomyopathy with left and right ventricular involvement, epidermolytic palmoplantar keratoderma, and woolly hair. The patient showed a severe heart phenotype with an early onset and rapid progression to heart failure at 4 years of age. Results A homozygous nonsense mutation, R1267X, was found in exon 23 of the desmoplakin gene, which results in an isoform specific truncation of the larger DSPI isoform. The loss of most of the DSPI specific rod domain and C‐terminal area was confirmed by Western blotting and immunofluorescence. We further showed that the truncated DSPI transcript is unstable, leading to a loss of DSPI. DSPI is reported to be an obligate constituent of desmosomes and the only isoform present in cardiac tissue. To address this, we reviewed the expression of DSP isoforms in the heart. Our data suggest that DSPI is the major cardiac isoform but we also show that specific compartments of the heart have detectable DSPII expression. Conclusions This is the first description of a phenotype caused by a mutation affecting only one DSP isoform. Our findings emphasise the importance of desmoplakin and desmosomes in epidermal and cardiac function and additionally highlight the possibility that the different isoforms of desmoplakin may have distinct functional properties within the desmosome. PMID:16467215

  10. DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bingzhen [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Shen, Chunzi [Centers for Disease Control and Prevention, Zibo (China); Yang, Liu; Li, Chunhui; Yi, Anji [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Wang, Zhiping, E-mail: zhipingw@sdu.edu.cn [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China)

    2013-12-01

    Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

  11. Early onset Morganella morganii sepsis in a newborn infant with emergence of cephalosporin resistance caused by depression of AMPC beta-lactamase production..

    Science.gov (United States)

    Sinha, Ajay K; Kempley, Stephen T; Price, Elizabeth; Sharma, Bal K; Livermore, David M

    2006-04-01

    A preterm infant with early onset Morganella morganii sepsis was treated with cefotaxime and gentamicin after confirmation of antimicrobial susceptibility. The infant developed persistent ventriculitis caused by the emergence of a cefotaxime-resistant Morganella variant with derepression of its AmpC beta-lactamase. When choosing antibiotic therapy, the risk of development of resistance to cephalosporins should be considered in infections caused by M. morganii and other Gram-negative organisms with inducible AmpC beta-lactamases.

  12. Real-World Assessment of Clinical Outcomes in Patients with Lower-Risk Myelofibrosis Receiving Treatment with Ruxolitinib

    Directory of Open Access Journals (Sweden)

    Keith L. Davis

    2015-01-01

    Full Text Available Few trial-based assessments of ruxolitinib in patients with lower-risk myelofibrosis (MF have been conducted, and no studies have made such assessments in a real-world population. We assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment using a retrospective, observational review of anonymized US medical record data of patients diagnosed with IPSS low-risk (n=25 or intermediate-1-risk (n=83 MF. The majority of patients were male (low risk, 60%; intermediate-1 risk, 69%. Most patients (92% and 77% were still receiving ruxolitinib at the medical record abstraction date (median observation/exposure time, 8 months. The proportion of patients with moderate or severe palpable splenomegaly (≥10 cm decreased from diagnosis (56% to best response (12%. Fatigue was reported in 47% of patients and was the most common constitutional symptom. For most symptoms in both risk groups, shifts in the distribution of severity from more to less severe from diagnosis to best response were observed. Both patients with low-risk and intermediate-1-risk MF experienced a substantial decrease in spleen size with ruxolitinib treatment in real-world settings. For most symptoms examined, there were distinct improvements in the distribution of severity during ruxolitinib treatment. These findings suggest that patients with lower-risk MF may benefit clinically from ruxolitinib treatment.

  13. Long-term results of a phase II trial of lenalidomide plus prednisone therapy for patients with myelofibrosis.

    Science.gov (United States)

    Chihara, Dai; Masarova, Lucia; Newberry, Kate J; Maeng, Hoyoung; Ravandi, Farhad; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2016-09-01

    Lenalidomide, with or without prednisone, is an active therapy for patients with myelofibrosis (MF). We provide an update of a phase II study of lenalidomide plus prednisone in patients with MF, after median follow up of 9 years. Forty patients were enrolled in the study and all patients were evaluable for response. Response to the treatment was reevaluated using IWG response criteria published in 2013: quality of response improved over time and overall response rate was 35%. Response in splenomegaly was seen in 39% of patients and anemia response in 32%. The median time to treatment failure (TTF) in all patients was 8.2 months and the median duration of response was 34.6 months. Response was highly durable in some patients: six patients (15%) had TTF for more than 60 months (5 years) and three patients are still on the treatment beyond 109 months (9 years). Complete and partial responses were seen in one and five patients, respectively, but achieving deeper response was not necessary for the response to be durable. New clinical studies are needed to explore safe and well tolerated lenalidomide-based combination strategies for patients with MF.

  14. Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts.

    Science.gov (United States)

    Passamonti, Francesco; Maffioli, Margherita; Cervantes, Francisco; Vannucchi, Alessandro Maria; Morra, Enrica; Barbui, Tiziano; Caramazza, Domenica; Pieri, Lisa; Rumi, Elisa; Gisslinger, Heinz; Knoops, Laurent; Kiladjian, Jean Jaques; Mora, Barbara; Hollaender, Norbert; Pascutto, Cristiana; Harrison, Claire; Cazzola, Mario

    2014-03-20

    The international prognostic scoring system (IPSS) provides reliable risk assessment in patients with primary myelofibrosis (PMF). Recent clinical trials in PMF patients with intermediate-2 or high IPSS risk have shown a survival advantage of ruxolitinib over placebo (COMFORT-1) or best available therapy (COMFORT-2). Because crossover was allowed in these studies, we analyzed the cohort of ruxolitinib-naive patients used for developing the dynamic IPSS (DIPSS). By adopting ad hoc statistical analyses, we compared survival from diagnosis of 100 PMF patients receiving ruxolitinib within COMFORT-2 with that of 350 patients of the DIPSS study. Subjects were properly matched, and both left-truncation and right-censoring were accounted in order to compare higher IPSS risks exclusively. Patients receiving ruxolitinib had longer survival (5 years, 95% confidence interval [CI]: 2.9-7.8 vs 3.5 years, 95% CI: 3.0-3.9) with a hazard ratio of 0.61 (95% CI: 0.41-0.91; P = .0148). This observation suggests that ruxolitinib may modify the natural history of PMF.

  15. Increased likelihood of post-polycythemia vera myelofibrosis in Ph-negative MPN patients with chromosome 12 abnormalities.

    Science.gov (United States)

    Benton, Christopher B; Tanaka, Maria; Wilson, Catherine; Pierce, Sherry; Zhou, Lingsha; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2015-04-01

    Chromosome 12 (Chr12) abnormalities have been described for individual patients with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPN), however the frequency, characteristics, and outcomes of such patients as a whole have not been investigated. We reviewed a database of 1787 consecutive Ph-neg MPN patients seen at our institution and determined that 2% of Ph-neg MPN patients harbored an alteration involving Chr12 by cytogenetic evaluation. Retrospective chart review revealed that patients with Chr12 abnormalities had a higher likelihood of having myelofibrosis (MF) compared to patients without a Chr12 abnormality, and were more likely to have post-polycythemia vera MF. The most common alterations in Chr12 in MF patients involved 12q13, 12q15, 12q24, and trisomy 12, and >40% of Chr12 Ph-neg MPN patients had cytogenetic evolution. Chr12 abnormalities did not significantly correlate with JAK2 status, progression to acute myeloid leukemia, or survival, however patients with 12q24 abnormalities trended toward poorer outcomes.

  16. Safety and efficacy of splenic irradiation in the treatment of patients with idiopathic myelofibrosis: a report on 15 patients.

    Science.gov (United States)

    Bouabdallah, R; Coso, D; Gonzague-Casabianca, L; Alzieu, C; Resbeut, M; Gastaut, J A

    2000-06-01

    Splenic irradiation in idiopathic myelofibrosis (IMF) has often been use d in selected situations when other therapies were unefficient or contraindicated. This could improve quality of life of patients, but literature remains rare in this field. We have assessed the impact of splenic irradiation in 15 patients with IMF. All of them were no longer responsive to usual treatments, and they presented at least one of the following features: constitutional symptoms, splenic pain, large splenic size, and anemia requiring >2 units of red blood cell transfusion per month. The planned schedule of radiotherapy consisted in daily fractions of 0.4-1 Gy. The median dose of radiotherapy per treatment was 9.8 Gy (range, 0.6-30.5). The overall response rate was 59% with a median duration of 10 months (range, 1-19). Splenic irradiation was more effective on constitutional symptoms, splenic pain, and spleen size. The best responses were noted when full doses of radiotherapy could be delivered, and when patients were previously fewly transfused. Splenic irradiation effectively palliates IMF-related symptoms, and constitute an alternative therapy for patients refractory to usual treatments.

  17. Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia

    Directory of Open Access Journals (Sweden)

    M B Agarwal

    2015-01-01

    Full Text Available According to the 2008 revision of the World Health Organization (WHO classification of myeloid malignancies, philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years. The MPN-Working Group (MPN-WG, a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India.This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India.

  18. Early developmental exposure to high fructose intake in rats with NaCl stimulation causes cardiac damage.

    Science.gov (United States)

    Araujo, I C; Andrade, R P; Santos, F; Soares, E S; Yokota, R; Mostarda, C; Fiorino, P; De Angelis, K; Irigoyen, M C; Morris, M; Farah, V

    2016-02-01

    Metabolic syndrome (MS) increases the risk of type 2 diabetes and cardiovascular disease. High consumption of fructose is a proposed cause of increased MS, manifested through hypertension, obesity, insulin resistance, and dyslipidemia. High NaCl also increases the risk of CD. The purpose of this study is to evaluate the influence of fructose and sodium on autonomic dysfunction and its relation with CD in MS. Fructose overload was started at weaning and continued through adulthood. Male Wistar rats (21 days) were divided into four groups: Control (C), fructose consumption (10%, F), NaCl consumption (salt 1% for the 10 last days, S), and fructose and NaCl (FS), and monitored for 8 weeks. Metabolic evaluations consisted of Lee index, glycemia, insulin and glucose tolerance tests, triglycerides, and total cholesterol measurements. Cardiovascular parameters measured were arterial pressure (AP) and cardiac function performed by echocardiography. They also measured the influence of renin angiotensin (RAS) and autonomic nervous systems by drug blockage with losartan, atropine, and atenolol. Energy analysis showed no change between groups. Fructose overload induced a MS state, confirmed by insulin resistance, glucose intolerance, and dyslipidemia. Fasting glucose was increased in F and FS rat groups compared with C and S groups. AP was higher in F, S, and FS groups in comparison with the C group. The hypotensive response after sympathetic blockade was increased in F, S, and FS versus C. The cardiac vagal tonus was reduced in F and FS animal groups. The intrinsic heart rate was decreased in the FS group (372 ± 9 bpm) compared with the C group (410 ± 13 bpm). The morphometric measurements evaluated through left ventricular diameter during diastole and the left ventricular diameter during systole decreased in the FS group (16 and 26%, respectively). Diastolic function was reduced in F and FS. The depressor response induced by losartan was increased in the F group in

  19. Ectopic expression of OsMADS45 activates the upstream genes Hd3a and RFT1 at an early development stage causing early flowering in rice.

    Science.gov (United States)

    Wang, Jiun-Da; Lo, Shuen-Fang; Li, Yan-Suan; Chen, Po-Ju; Lin, Shih-Yun; Ho, Teh-Yuan; Lin, Jenq-Horng; Chen, Liang-Jwu

    2013-12-01

    The rice gene, OsMADS45, which belongs to the MADS-box E class gene, participates in the regulation of floral development. Previous studies have revealed that ectopic expression of OsMADS45 induces early flowering and influences reduced plant height under short-day (SD) conditions. However, the regulation mechanism of OsMADS45 overexpression remains unknown. We introduce an OsMADS45 overexpression construct Ubi:OsMADS45 into TNG67 plants (an Hd1 (Heading date 1) and Ehd1 (Early heading date 1) defective rice cultivar grown in Taiwan), and we analyzed the expression patterns of various floral regulators to understand the regulation pathways affected by OsMADS45 expression. The transgenic rice exhibit a heading date approximately 40 days earlier than that observed in TNG67 plants, and transgenic rice display small plant size and low grain yield. OsMADS45 overexpression did not alter the oscillating rhythm of the examined floral regulatory genes but advanced (by approximately 20 days) the up-regulate of two florigens, Hd3a (Heading Date 3a) and RFT1 (RICE FLOWERING LOCUS T1) and suppressed the expression of Hd1 at the juvenile stage. The expression levels of OsMADS14 and OsMADS18, which are two well-known reproductive phase transition markers, were also increased at early developmental stages and are believed to be the major regulators responsible for early flowering in OsMADS45-overexpressing transgenic rice. OsMADS45 overexpression did not influence other floral regulator genes upstream of Hd1 and Ehd1, such as OsGI (OsGIGANTEA), Ehd2/Osld1/RID1 and OsMADS50. These results indicate that in transgenic rice, OsMADS45 overexpressing ectopically activates the upstream genes Hd3a and RFT1 at early development stage and up-regulates the expression of OsMADS14 and OsMADS18, which induces early flowering.

  20. The dysfunction of CD4(+CD25(+ regulatory T cells contributes to the abortion of mice caused by Toxoplasma gondii excreted-secreted antigens in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Jin-ling Chen

    Full Text Available Toxoplasma gondii is an opportunistic intracellular parasite that is highly prevalent in human and warm-blooded animals throughout the world, leading to potentially severe congenital infections. Although the abortion caused by T. gondii is believed to be dependent on the timing of maternal infection during pregnancy, the mechanism remains unclear. This study was focused on the effects of T. gondii excreted-secreted antigens on pregnant outcomes and CD4(+CD25(+ Foxp3(+ regulatory T cells at different stages of pregnancy. The results showed that in mice the frequency and suppressive function of CD4(+CD25(+ regulatory cells were diminished after injection of T. gondii excreted-secreted antigens at early and intermediate stages of pregnancy. The abortion caused by T. gondii excreted-secreted antigens at early pregnancy could be partly prevented by adoptively transferring of CD4(+CD25(+ cells from the mice injected with T. gondii excreted-secreted antigens at late pregnancy, but not from the mice with the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted antigens induced apoptosis of CD4(+CD25(+ regulatory cells of mice in early and intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and Bcl-2/Bax ratio. This study provides new insights into the mechanism that T. gondii infection is the high risk factor for abortion in early pregnancy.

  1. A biological method to monitor early effects of the air pollution caused by the industrial exploitation of geothermal energy

    Energy Technology Data Exchange (ETDEWEB)

    Paoli, Luca [Department of Environmental Science ' G. Sarfatti' , University of Siena, Via P.A. Mattioli 4, I-53100 Siena (Italy); Loppi, Stefano [Department of Environmental Science ' G. Sarfatti' , University of Siena, Via P.A. Mattioli 4, I-53100 Siena (Italy)], E-mail: loppi@unisi.it

    2008-09-15

    The suitability of a set of ecophysiological parameters, to be used as early warning indicator to detect signs of a worsening environment around geothermal power plants, was tested by comparison with the diversity of epiphytic lichens, a well-established indicator of geothermal air pollution. Samples of the lichen Evernia prunastri were transplanted around a geothermal power plant at Larderello (Tuscany, Italy) and at a control site, and integrity of cell membranes, concentration of chlorophyll a, b and carotenoids, chlorophyll integrity and variations in pH of thalli were measured. The results showed that cell membrane damage, expressed by changes in electrical conductivity, could be used to detect early (exposure periods as short as 1 month) deleterious effects of geothermal air pollution. - Biomonitoring early effects of geothermal air pollution.

  2. Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis

    DEFF Research Database (Denmark)

    Silver, Richard T; Kiladjian, Jean-Jacques; Hasselbalch, Hans K

    2013-01-01

    Recombinant IFN-α (rIFN-α) induces complete hematologic remissions in patients with myeloproliferative neoplasms (MPNs), but its use has been limited by side effects owing to the relatively high doses used. Now, low-dose rIFN-α is stressed, starting relatively early in the course of the MPNs. In ...

  3. Identification of submicroscopic genetic changes and precise breakpoint mapping in myelofibrosis using high resolution mate-pair sequencing.

    Science.gov (United States)

    Lasho, Terra; Johnson, Sarah H; Smith, David I; Crispino, John D; Pardanani, Animesh; Vasmatzis, George; Tefferi, Ayalew

    2013-09-01

    We used high resolution mate-pair sequencing (HRMPS) in 15 patients with primary myelofibrosis (PMF): eight with normal karyotype and seven with PMF-characteristic cytogenetic abnormalities, including der(6)t(1;6)(q21-23;p21.3) (n = 4), der(7)t(1;7)(q10;p10) (n = 2), del(20)(q11.2q13.3) (n = 3), and complex karyotype (n = 1). We describe seven novel deletions/translocations in five patients (including two with normal karyotype) whose breakpoints were PCR-validated and involved MACROD2, CACNA2D4, TET2, SGMS2, LRBA, SH3D19, INTS3, FOP (CHTOP), SCLT1, and PHF17. Deletions with breakpoints involving MACROD2 (lysine deacetylase; 20p12.1) were recurrent and found in two of the 15 study patients. A novel fusion transcript was found in one of the study patients (INTS3-CHTOP), and also in an additional non-study patient with PMF. In two patients with der(6)t(1;6)(q21-23;p21.3), we were able to map the precise translocation breakpoints, which involved KCNN3 and GUSBP2 in one case and HYDIN2 in another. This study demonstrates the utility of HRMPS in uncovering submicroscopic deletions/translocations/fusions, and precise mapping of breakpoints in those with overt cytogenetic abnormalities. The overall results confirm the genetic heterogeneity of PMF, given the low frequency of recurrent specific abnormalities, identified by this screening strategy. Currently, we are pursuing the pathogenetic relevance of some of the aforementioned findings.

  4. A biological method to monitor early effects of the air pollution caused by the industrial exploitation of geothermal energy.

    Science.gov (United States)

    Paoli, Luca; Loppi, Stefano

    2008-09-01

    The suitability of a set of ecophysiological parameters, to be used as early warning indicator to detect signs of a worsening environment around geothermal power plants, was tested by comparison with the diversity of epiphytic lichens, a well-established indicator of geothermal air pollution. Samples of the lichen Evernia prunastri were transplanted around a geothermal power plant at Larderello (Tuscany, Italy) and at a control site, and integrity of cell membranes, concentration of chlorophyll a, b and carotenoids, chlorophyll integrity and variations in pH of thalli were measured. The results showed that cell membrane damage, expressed by changes in electrical conductivity, could be used to detect early (exposure periods as short as 1 month) deleterious effects of geothermal air pollution.

  5. A der(18)t(9;18)(p13;p11) and a der(9;18)(p10;q10) in polycythemia vera associated with a hyperproliferative phenotype in transformation to postpolycythemic myelofibrosis

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Hasselbalch, Hans Carl; Pallisgaard, Niels

    2007-01-01

    [two with PV, one with PV in transformation to idiopathic myelofibrosis (IMF) and one IMF patient], with the distinct karyotypic abberations der(18) t(9;18) (p13;p11) and der(9;18)(p10;q10). Two patients had hyperproliferative PV and two had "transitional PV" and IMF, respectively. All four patients...

  6. Extrahepatic Manifestations of Hepatitis B Virus Infection: Addison’s Disease and Myelofibrosis in a Patient with Persistent Hepatitis B Surface Antigenemia

    Directory of Open Access Journals (Sweden)

    François Somlo

    1993-01-01

    Full Text Available A 60-year-old white male patient was admitted to the hospital with acute abdominal pain, seemingly a self-limited ileus. He was found to be hepatitis B surface antigen (HBsAg-positive. Previous dental treatment was suspected to be the initial source of the infection with hepatitis B virus. Five months later he was re-admitted with a diagnosis of adrenal insufficiency (Addison’s disease which responded well to steroids. Four years later he developed fever and leucocytosis. A bone marrow biopsy revealed myelofibrosis. He had several episodes of pyrexia during his lifetime. After a 12-year period the patient suffered a fatal myocardial infarction. At autopsy the adrenal glands were reduced to scarred remnants and HBsAg was found to be present in the residual adrenocortical cells by immunoflouresence methods. Bone marrow at autopsy revealed myelosclerosis as well HBsAg (via immunofluoresence. Hepatitis B virus was therefore closely correlated with the development of Addison’s disease and myelofibrosis in this case.

  7. Myelofibrosis-Associated Lymphoproliferative Disease: Retrospective Study of 16 Cases and Literature Review

    Directory of Open Access Journals (Sweden)

    A. Etienne

    2009-01-01

    Conclusions. MF-associated NHL is a rare manifestation which may be associated with all types of NHL and its presence does not seem to confer a poor prognosis. A search for lymphoproliferation should be considered when the cause of MF is not apparent.

  8. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

    DEFF Research Database (Denmark)

    Clayton, Emma L; Mancuso, Renzo; Nielsen, Troels Tolstrup

    2017-01-01

    Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD...

  9. Early lingual frenectomy assisted by CO2 laser helps prevention and treatment of functional alterations caused by ankyloglossia.

    Science.gov (United States)

    Fiorotti, Renata C; Bertolini, Milene M; Nicola, Jorge H; Nicola, Ester M D

    2004-11-01

    Incorrectly produced speech sounds, the presence of dentofacial alterations and acquired functional adaptations may be due to a short and inadequate lingual frenum. When frenectomy is indicated, it should be performed as early as possible to prevent functional alterations. This study presents a literature review on correct lingual positioning in relation to orthodontic and phonetic function as well as an assessment of 15 patients who underwent frenectomy utilizing the carbon dioxide laser. The results demonstrated that this technique is safe, effective and perfect for use in young children and can be performed in an outpatient unit.

  10. Analysis of the Causes of Elevated C-Reactive Protein Level in the Early Postoperative Period After Primary Total Knee Arthroplasty.

    Science.gov (United States)

    Kim, Tae Won; Kim, Dong Hwan; Oh, Won Seuk; Sim, Jae Ang; Lee, Yong Seuk; Lee, Beom Koo

    2016-09-01

    Measurement of C-reactive protein (CRP) levels as a screening test for acute periprosthetic joint infection has high sensitivity and low specificity. We performed the present study to analyze the causes of elevated CRP levels in the early postoperative period after primary total knee arthroplasty (TKA). This study is intended to help the postoperative care of patients through understanding the factors associated with postoperative elevation of CRP. The records for 627 patients who underwent primary TKA between January 2005 and May 2013 were examined. We excluded 50 patients for whom TKA with inflammatory arthritis or revision TKA was performed. We measured serial CRP levels during the 4-week early postoperative period in all included cases to find the cases that showed a CRP pattern of elevation-depression-elevation (a bimodal pattern). We analyzed the causes of re-elevated CRP levels in patients with a bimodal pattern of CRP change. Of the 577 included patients, 76 showed bimodal CRP elevation patterns. Eighteen elevations were caused by postoperative infections (periprosthetic infection), 10 by cardiovascular problems, 11 by gastrointestinal problems, 12 by urologic problems, 10 by respiratory problems, and 15 had unknown origins. Our study shows that elevated CRP levels after TKA can have various causes. Although there may be other causes for an elevated CRP, it is essential to perform a work-up for prosthetic joint infections. In addition, there seems to be a need to evaluate noninfectious causes and infection of other sites, in addition to periprosthetic infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Comparison of changes in etiologic microorganisms causing early-onset neonatal sepsis between preterm labor and preterm premature rupture of membranes.

    Science.gov (United States)

    Jeong, Heejeong; Han, Su-jin; Yoo, Ha-Na; Choi, Suk-Joo; Oh, Soo-Young; Kim, Yae-Jean; Roh, Cheong-Rae; Kim, Jong-Hwa

    2015-11-01

    To investigate changes in the etiologic microorganisms causing early-onset neonatal sepsis (EONS) in preterm labor (PTL) or preterm premature rupture of membranes (pPROM) cases over the past 16 years and to analyze the associated factors. We included consecutive singleton pregnancies delivered before 34 weeks due to PTL or pPROM. The etiologic microorganisms causing EONS in PTL and pPROM cases were compared between period 1 (1996-2004) and period 2 (2005-2012). There was no difference in the incidence of Gram-positive bacteria causing EONS between period 1 and 2, either in PTL (2.0% versus 2.1%, p = 1.0) or in pPROM (1.5% versus 1.6%, p = 1.0). However, the incidence of EONS caused by Gram-negative bacteria was significantly increased in pPROM (0.6% versus 2.7%, p = 0.040) during period 2, compared to period 1; but not in PTL (0.3% versus 1.2%, p = 0.211). Multivariable analysis revealed that a prolonged ROM-to-delivery interval (>7 d) was significantly associated with EONS caused by Gram-negative bacteria in pPROM (odds ratio: 6.6, 95% confidence interval: 1.4-31.8, p = 0.018). The etiologic microorganisms causing EONS have changed over the past 16 years in pPROM cases but not in PTL cases.

  12. Development of a Semi-nested PCR-Based Method for Specific and Rapid Detection of Alternaria solani Causing Potato Early Blight in Soil.

    Science.gov (United States)

    Gu, Qing; Yang, Zhi-Hui; Zhao, Dong-Mei; Zhang, Dai; Wang, Qian; Ma, Li-Song; Zhu, Jie-Hua

    2017-09-01

    Early blight, caused by Alternaria solani, is one of the most devastating diseases of potato that causes severe yield loss worldwide. The infected potato debris existed in the soil serve as the initial infection sources for the next growing potato. Current identification of A. solani in soil relies primarily on cultural and morphological characteristics, which are time-consuming and inaccurate. In this study, a semi-nested PCR method was developed using primers based on internal transcribed spacer region that is specific to A. solani. 20 isolates including 6 Alternaria species and 10 other species of common potato pathogens were used to examine the specificity of the primers. The primer set ptAsQ-F/ptAs-R was highly specific to A. solani, as a product of 251 bp was amplified only from A. solani isolates and no amplification signal was observed from other tested species. The sensitivity of this method determined using A. solani genomic DNA was 10 fg. This PCR assay was also successfully employed to detect A. solani in soil with the detection sensitivity of one conidia spore in 0.5 g of soil. To the best of our knowledge, this is the first report of molecular detection of A. solani in soil, which provides a useful tool for early and rapid detection of early blight in soil before next growing season.

  13. [Acute intussusception, a rare cause of small bowel obstruction in premature neonates: the advantages of early diagnosis].

    Science.gov (United States)

    Boubal, M; Jacquot, A; Baud, C; Allal, H; Cambonie, G; Picaud, J-C

    2010-10-01

    We report a case of intussusception in a premature neonate who presented with early signs of upper gastrointestinal tract obstruction. Diagnosing acute intussusception in premature infants is difficult because of its infrequency relative to other neonatal abdominal problems and because the clinical symptomatology shows similarities with that of necrotizing enterocolitis. In the reported case, the diagnosis was made by sonography. Unlike full-term neonates, the presence of a pathological lead point is very infrequent. The intussusception is predominantly located in the small bowel and is most often associated with bowel compromise. This disease should be considered in all neonates with signs of intestinal obstruction to permit a better prognosis via prompt surgical intervention.

  14. A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia.

    Science.gov (United States)

    Corbett, Mark A; Schwake, Michael; Bahlo, Melanie; Dibbens, Leanne M; Lin, Meng; Gandolfo, Luke C; Vears, Danya F; O'Sullivan, John D; Robertson, Thomas; Bayly, Marta A; Gardner, Alison E; Vlaar, Annemarie M; Korenke, G Christoph; Bloem, Bastiaan R; de Coo, Irenaeus F; Verhagen, Judith M A; Lehesjoki, Anna-Elina; Gecz, Jozef; Berkovic, Samuel F

    2011-05-13

    The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.

  15. A Mutation in the Golgi Qb-SNARE Gene GOSR2 Causes Progressive Myoclonus Epilepsy with Early Ataxia

    Science.gov (United States)

    Corbett, Mark A.; Schwake, Michael; Bahlo, Melanie; Dibbens, Leanne M.; Lin, Meng; Gandolfo, Luke C.; Vears, Danya F.; O'Sullivan, John D.; Robertson, Thomas; Bayly, Marta A.; Gardner, Alison E.; Vlaar, Annemarie M.; Korenke, G. Christoph; Bloem, Bastiaan R.; de Coo, Irenaeus F.; Verhagen, Judith M.A.; Lehesjoki, Anna-Elina; Gecz, Jozef; Berkovic, Samuel F.

    2011-01-01

    The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi. PMID:21549339

  16. Intra- and trans-generational costs of reduced female body size caused by food limitation early in life in mites.

    Directory of Open Access Journals (Sweden)

    Andreas Walzer

    Full Text Available Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs.Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons.Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism - females are the larger sex and thus more strongly affected by maternal stress than the smaller males - and to sexually selected lower plasticity of male body size.

  17. Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens.

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    Magnus Elfwing

    Full Text Available Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of stress experienced during the first weeks of life. Chicks from a commercial egg-laying hybrid were exposed to stress by inducing periods of social isolation during their first three weeks of life, followed by a broad behavioural, physiological and genomic characterization throughout life. Early stressed males, but not females, where more anxious in an open field-test, stayed shorter in tonic immobility and tended to have delayed sexual maturity, as shown by a tendency for lower levels of testosterone compared to controls. While early stressed females did not differ from non-stressed in fear and sexual maturation, they were more socially dominant than controls. The differential gene expression profile in hypothalamus was significantly correlated from 28 to 213 days of age in males, but not in females. In conclusion, early stress had a more pronounced long-term effect on male than on female chickens, as evidenced by behavioral, endocrine and genomic responses. This may either be attributed to inherent sex differences due to evolutionary causes, or possibly to different stress related selection pressures on the two sexes during commercial chicken breeding.

  18. Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens.

    Science.gov (United States)

    Elfwing, Magnus; Nätt, Daniel; Goerlich-Jansson, Vivian C; Persson, Mia; Hjelm, Jonas; Jensen, Per

    2015-01-01

    Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of stress experienced during the first weeks of life. Chicks from a commercial egg-laying hybrid were exposed to stress by inducing periods of social isolation during their first three weeks of life, followed by a broad behavioural, physiological and genomic characterization throughout life. Early stressed males, but not females, where more anxious in an open field-test, stayed shorter in tonic immobility and tended to have delayed sexual maturity, as shown by a tendency for lower levels of testosterone compared to controls. While early stressed females did not differ from non-stressed in fear and sexual maturation, they were more socially dominant than controls. The differential gene expression profile in hypothalamus was significantly correlated from 28 to 213 days of age in males, but not in females. In conclusion, early stress had a more pronounced long-term effect on male than on female chickens, as evidenced by behavioral, endocrine and genomic responses. This may either be attributed to inherent sex differences due to evolutionary causes, or possibly to different stress related selection pressures on the two sexes during commercial chicken breeding.

  19. Targeted high-throughput sequencing identifies a TARDBP mutation as a cause of early-onset FTD without motor neuron disease.

    Science.gov (United States)

    Synofzik, Matthis; Born, Christoph; Rominger, Axel; Lummel, Nina; Schöls, Ludger; Biskup, Saskia; Schüle, Cornelius; Grasshoff, Ute; Klopstock, Thomas; Adamczyk, Christopher

    2014-05-01

    Targeted high-throughput sequencing of many amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) genes in parallel has the potential to reveal novel ALS- and/or FTD-phenotypes and to provide missing links on the ALS-FTD continuum. For example, although the 43-kDa transactive response DNA binding protein is the major pathologic hallmark linking ALS and FTD, mutations in the gene encoding 43-kDa transactive response DNA binding protein (TARDBP) have been appreciated only as a cause of ALS-phenotypes, but not yet of pure FTD. Thus, the genetic link is not yet well substantiated that TARDBP mutations can cause the full spectrum of the ALS-FTD continuum. High-throughput sequencing of 18 ALS and FTD genes in an index patient presenting with early-onset pure (behavioral) FTD and a positive family history for ALS revealed an established TARDBP mutation, A382T. This finding demonstrates that a TARDPB mutation can cause early-onset pure FTD without evidence for ALS even in advanced FTD disease stages. Moreover, it indicates that TARDPB screening might be considered even in young patients with "pure" neuropsychiatric disturbances and without evidence of neurodegenerative disease in the parental generation.

  20. What caused G. truncatulinoides to calcify in shallower water during the early Holocene in the western Atlantic / Gulf of Mexico?

    Energy Technology Data Exchange (ETDEWEB)

    Cleroux, Caroline; Lynch-Stieglitz, Jean, E-mail: ccleroux@ldeo.columbia.ed [School of Earth and Environmental Sciences, Georgia Institute of Technology, Atlanta, GA (United States)

    2010-03-15

    In a recent paper we reconstructed the calcification depth of G. truncatulinoides since the last deglaciation in the Florida Straits. We highlighted a significantly different calcification depth between 8-10 ka and the late Holocene. This migration was found in three different cores over the western North Atlantic American continental margin. This paper presents new Mg/Ca ratio data on G. truncatulinoides in the Florida Strait and new stable isotopic measurements on G. crassaformis in the Gulf of Mexico. Preliminary interpretation to understand the cause of G. truncatulinoides migration in the water column at the beginning of the Holocene is given.

  1. An unusual cause of S1 radicular pain presenting as early phantom pain in a transfemoral amputee: a case report.

    Science.gov (United States)

    Smuck, Matthew; Christensen, Sara; Lee, Stan S; Sagher, Oren

    2008-01-01

    Recent epidemiologic studies have shown back pain to be a significant cause of pain in lower-limb amputees, but only a handful of cases have reported sciatica in amputees. The symptoms are usually described as a phantom pain or neuropathic pain in the residual limb that is often refractory to conventional treatments. These symptoms typically occur with back pain and are distinct from the patient's usual symptoms. Interestingly, back pain is not a universal finding. We present a patient with presumed phantom limb pain subsequently discovered to be caused by an S1 radiculopathy. This patient's supposed phantom pain persisted despite multiple medication trials. Initial work-up revealed a sciatic neuroma at the stump. Treatments targeting this neuroma were unsuccessful. Further evaluation found that a sacroiliac joint screw placed to stabilize a pelvic fracture had intruded into the S1 neuroforamen. A diagnostic S1 nerve block temporarily relieved the patient's pain, and the screw was removed. Pain persisted and a spinal cord stimulator was placed resulting in improvement of his pain. Because conventional diagnostic tests are limited, including physical exam and electromyography, a fluoroscopically guided selective spinal nerve block proved to be a useful diagnostic tool in this patient.

  2. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  3. Takotsubo Syndrome as a Cause of False Acute Abdomen in the Early Postoperative Period After Bariatric Surgery-a Report of Two Cases.

    Science.gov (United States)

    Viegas, Fabio; Viegas, Carla; França, Enio; Kleuser, Klaus; de Barros, Fernando

    2016-10-01

    Takotsubo syndrome, also known as broken-heart syndrome, stress-induced cardiomyopathy or transient apical ballooning syndrome, is a transient disorder characterized by segmental left ventricular failure in the absence of obstructive coronary artery disease. Most cases of Takotsubo syndrome are caused by acute stress that leads to a sudden, temporary weakening of the cardiac musculature. This stress triggers a rise in circulating catecholamine levels that results in acute ventricular dysfunction. In this report, we describe two cases of Takotsubo syndrome in the early postoperative period after bariatric surgery.

  4. Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.

    Science.gov (United States)

    Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P

    2016-12-01

    Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.

  5. Early regression of spermatogenesis in boars of an inbred Duroc strain caused by incident orchitis/epididymo-orchitis.

    Science.gov (United States)

    Noguchi, Junko; Nakai, Michiko; Kikuchi, Kazuhiro; Kaneko, Hiroyuki; Imaeda, Noriaki

    2013-01-01

    In the process of establishment of an inbred Duroc pig strain, males with size asymmetry of the testes were frequently observed. To clarify the possible causes of this asymmetry, we examined the testes and epididymides of 67 males of the F4-F7 generations at 35-100 weeks of age. Testicular weights showed a wide variation (120-610 g). When the weights of the testes were compared bilaterally, 35 of the 67 males showed more than a 10% difference. Histological examination of testes from this asymmetry group revealed a range of seminiferous tubule disruption including disappearance of all germ cells, but not Sertoli cells, in the epithelium. Focal lesions associated with the degenerated tubules were observed. Trends of incident fibrosis or hyalinization of these lesions were seen in aged males of the asymmetry group. Besides this abnormality of spermatogenesis, infiltration of mononuclear inflammatory cells around the tubule was frequently observed in the asymmetry group (32.9%, compared with 1.6% in males showing testis symmetry). In severe cases, the inflammatory cells were concentrated in the intertubular region instead of Leydig cells. Cellular infiltration was also observed around the epididymal duct and blood vessels, but its incidence did not differ between the symmetry and asymmetry groups. Testicular testosterone levels were significantly increased in the asymmetry group, but those of E2 and inhibin did not differ between the two groups. These histopathological features indicate that disruption of spermatogenesis after orchitis/epididymo-orchitis could induce testicular atrophy. Genetic predispositions for this trait may cause prevalent retrograde infections, resulting in orchitis/epididymo-orchitis.

  6. The VLF fingerprint of elves: Step-like and long-recovery early VLF perturbations caused by powerful ±CG lightning EM pulses

    Science.gov (United States)

    Haldoupis, Christos; Cohen, Morris; Arnone, Enrico; Cotts, Benjamin; Dietrich, Stefano

    2013-08-01

    Subionospheric VLF recordings are investigated in relation with intense cloud-to-ground (CG) lightning data. Lightning impacts the lower ionosphere via heating and ionization changes which produce VLF signal perturbations known as early VLF events. Typically, early events recover in about 100 s, but a small subclass does not recover for many minutes, known as long-recovery early events (LORE). In this study, we identify LORE as a distinct category of early VLF events, whose signature may occur either on its own or alongside the short-lived typical early VLF event. Since LORE onsets coincide with powerful lightning strokes of either polarity (±), we infer that they are due to long-lasting ionization changes in the uppermost D region ionosphere caused by electromagnetic pulses emitted by strong ± CG lightning peak currents of typically > 250 kA, which are also known to generate elves. The LORE perturbations are detected when the discharge is located within ~250 km from the great circle path of a VLF transmitter-receiver link. The probability of occurrence increases with stroke intensity and approaches unity for discharges with peak currents ≥ ~300 kA. LOREs are nighttime phenomena that occur preferentially, at least in the present regional data set, during winter when strong ± CG discharges are more frequent and intense. The evidence suggests LORE as a distinct signature representing the VLF fingerprint of elves, a fact which, although was predicted by theory, it escaped identification in the long-going VLF research of lightning effects in the lower ionosphere.

  7. Early exposure of bay scallops (Argopecten irradians to high CO₂ causes a decrease in larval shell growth.

    Directory of Open Access Journals (Sweden)

    Meredith M White

    Full Text Available Ocean acidification, characterized by elevated pCO₂ and the associated decreases in seawater pH and calcium carbonate saturation state (Ω, has a variable impact on the growth and survival of marine invertebrates. Larval stages are thought to be particularly vulnerable to environmental stressors, and negative impacts of ocean acidification have been seen on fertilization as well as on embryonic, larval, and juvenile development and growth of bivalve molluscs. We investigated the effects of high CO₂ exposure (resulting in pH = 7.39, Ω(ar = 0.74 on the larvae of the bay scallop Argopecten irradians from 12 h to 7 d old, including a switch from high CO₂ to ambient CO₂ conditions (pH = 7.93, Ω(ar = 2.26 after 3 d, to assess the possibility of persistent effects of early exposure. The survival of larvae in the high CO₂ treatment was consistently lower than the survival of larvae in ambient conditions, and was already significantly lower at 1 d. Likewise, the shell length of larvae in the high CO₂ treatment was significantly smaller than larvae in the ambient conditions throughout the experiment and by 7 d, was reduced by 11.5%. This study also demonstrates that the size effects of short-term exposure to high CO₂ are still detectable after 7 d of larval development; the shells of larvae exposed to high CO₂ for the first 3 d of development and subsequently exposed to ambientCO₂ were not significantly different in size at 3 and 7 d than the shells of larvae exposed to high CO₂ throughout the experiment.

  8. Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria.

    Science.gov (United States)

    Oláhová, Monika; Thompson, Kyle; Hardy, Steven A; Barbosa, Inês A; Besse, Arnaud; Anagnostou, Maria-Eleni; White, Kathryn; Davey, Tracey; Simpson, Michael A; Champion, Michael; Enns, Greg; Schelley, Susan; Lightowlers, Robert N; Chrzanowska-Lightowlers, Zofia M A; McFarland, Robert; Deshpande, Charu; Bonnen, Penelope E; Taylor, Robert W

    2017-01-01

    Mitochondrial diseases collectively represent one of the most heterogeneous group of metabolic disorders. Symptoms can manifest at any age, presenting with isolated or multiple-organ involvement. Advances in next-generation sequencing strategies have greatly enhanced the diagnosis of patients with mitochondrial disease, particularly where a mitochondrial aetiology is strongly suspected yet OXPHOS activities in biopsied tissue samples appear normal. We used whole exome sequencing (WES) to identify the molecular basis of an early-onset mitochondrial syndrome-pathogenic biallelic variants in the HTRA2 gene, encoding a mitochondria-localised serine protease-in five subjects from two unrelated families characterised by seizures, neutropenia, hypotonia and cardio-respiratory problems. A unifying feature in all affected children was 3-methylglutaconic aciduria (3-MGA-uria), a common biochemical marker observed in some patients with mitochondrial dysfunction. Although functional studies of HTRA2 subjects' fibroblasts and skeletal muscle homogenates showed severely decreased levels of mutant HTRA2 protein, the structural subunits and complexes of the mitochondrial respiratory chain appeared normal. We did detect a profound defect in OPA1 processing in HTRA2-deficient fibroblasts, suggesting a role for HTRA2 in the regulation of mitochondrial dynamics and OPA1 proteolysis. In addition, investigated subject fibroblasts were more susceptible to apoptotic insults. Our data support recent studies that described important functions for HTRA2 in programmed cell death and confirm that patients with genetically-unresolved 3-MGA-uria should be screened by WES with pathogenic variants in the HTRA2 gene prioritised for further analysis.

  9. Early detection of injuries in leaves of Clusia hilariana Schltdl. (Clusiaceae caused by particulate deposition of iron

    Directory of Open Access Journals (Sweden)

    Diego Ismael Rocha

    2014-06-01

    Full Text Available This study aims to evaluate the prognostic value of microscopic parameters of asymptomatic leaves of Clusia hilariana Schltdl. subjected to particulate deposition of iron (2.14 mg cm-2 day-1 for 45 consecutive days. Samples of young and expanded leaves without symptoms were collected and subjected to light and scanning electron microscopy techniques. The height of the epidermal cells on both surfaces of the leaf and the thickness of the hypodermis, the chlorophyll parenchyma, and the leaf blade were measured. Micromorphological injury occurred in the abaxial surface of young leaves and on both surfaces of expanded leaves. Erosion of the epicuticular wax and cuticle rupture were frequent on the adaxial surface, while on the abaxial surface of both leaves there was a loss of sinuosity on the anticlinal wall of the epidermal cells, stomatal deformity and obstruction. Micromorphometric alterations were seen in all leaf tissues except in the height of epidermic cells, probably due to the thick cuticle and prominent cuticular flanges. The highest difference in thickness of the leaf blade was seen in young leaves of plants subjected to SPMFe, indicating greater sensibility to particulate iron in comparison to the expanded leaves. The micromorphological and micromorphometric alterations in the leaf blade of Clusia hilariana Schltdl. showed the prognostic potential of these tools on the evaluation of impacts caused by the deposition of particulate matter, especially in the 'Restinga' natural vegetation, where the exposure is increasing due to the presence of iron ore industry in their surroundings.

  10. Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment.

    Science.gov (United States)

    Cechetti, Fernanda; Pagnussat, Aline S; Worm, Paulo V; Elsner, Viviane Rostirolla; Ben, Juliana; da Costa, Marcelo Siveira; Mestriner, Régis; Weis, Simone Nardin; Netto, Carlos Alexandre

    2012-01-04

    Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage. Adult male Wistar rats were submitted to the modified 2VO method, with the right common carotid artery being occluded first and the left one week later, and tested seven days, three and six months after the ischemic event. A significant cognitive deficit was found in both reference and working spatial memory, as well as in the object recognition task, three and six months after surgery. Neuronal death and reactive astrogliosis were already present at 7 days and continued for up to 3 months after the occlusion; interestingly, there was no significant reduction in hippocampal volume. Present data suggests that cognitive impairment caused by brain hypoperfusion is long - lasting and persists beyond the time point of recovery from glial activation and neuronal loss. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy.

    Science.gov (United States)

    Smets, Katrien; Duarri, Anna; Deconinck, Tine; Ceulemans, Berten; van de Warrenburg, Bart P; Züchner, Stephan; Gonzalez, Michael Anthony; Schüle, Rebecca; Synofzik, Matthis; Van der Aa, Nathalie; De Jonghe, Peter; Verbeek, Dineke S; Baets, Jonathan

    2015-07-21

    Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. Whole exome sequencing in a cerebellar ataxia patient and subsequent immunocytochemistry, immunoblotting and patch clamp assays of the channel were performed. A de novo KCND3 mutation (c.877_885dupCGCGTCTTC; p.Arg293_Phe295dup) was found duplicating the RVF motif and thereby adding an extra positive charge to voltage-gated potassium 4.3 (Kv4.3) in the voltage-sensor domain causing a severe shift of the voltage-dependence gating to more depolarized voltages. The patient displayed a severe phenotype with early onset cerebellar ataxia complicated by intellectual disability, epilepsy, attention deficit hyperactivity disorder, strabismus, oral apraxia and joint hyperlaxity. We identified a de novo KCND3 mutation causing the most marked change in Kv4.3's channel properties reported so far, which correlated with a severe and unique spinocerebellar ataxia (SCA) type 19/22 disease phenotype.

  12. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  13. Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.

    Science.gov (United States)

    Thompson, Kyle; Majd, Homa; Dallabona, Christina; Reinson, Karit; King, Martin S; Alston, Charlotte L; He, Langping; Lodi, Tiziana; Jones, Simon A; Fattal-Valevski, Aviva; Fraenkel, Nitay D; Saada, Ann; Haham, Alon; Isohanni, Pirjo; Vara, Roshni; Barbosa, Inês A; Simpson, Michael A; Deshpande, Charu; Puusepp, Sanna; Bonnen, Penelope E; Rodenburg, Richard J; Suomalainen, Anu; Õunap, Katrin; Elpeleg, Orly; Ferrero, Ileana; McFarland, Robert; Kunji, Edmund R S; Taylor, Robert W

    2016-10-06

    Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations. All affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle. Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of the seven subjects, and the other three case subjects harbored the same c.703C>G (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of AAC1 protein levels and loss of respiratory chain complexes containing mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant proteins are severely impaired in ADP/ATP transport, affecting most likely the substrate binding and mechanics of the carrier, respectively. This highly reduced capacity for transport probably affects mitochondrial DNA maintenance and in turn respiration, causing a severe energy crisis. The confirmation of the pathogenicity of these de novo SLC25A4 mutations highlights a third distinct clinical phenotype associated with mutation of this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo mutations, which has significant implications for the application and analysis of whole-exome sequencing data in mitochondrial disease. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

    Science.gov (United States)

    Mascarenhas, John O.; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M.; Savona, Michael R.; Paquette, Ronald; Turner, A. Robert; Coughlin, Paul; Winton, Elliott; Burn, Timothy C.; O’Neill, Peter; Clark, Jason; Hunter, Deborah; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan

    2017-01-01

    Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×109/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1–24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression. PMID:27789678

  15. Correlation of JAK2V617F mutational status in primary myelofibrosis with clinico-hematologic characteristics and international prognostic scoring system scoring: A single center experience

    Directory of Open Access Journals (Sweden)

    Neha Singh

    2015-01-01

    Full Text Available Introduction: Somatic mutation in the exon 14 of Janus Kinase 2 gene is an established diagnostic marker in bcr-abl negative myeloproliferative neoplasms, especially primary idiopathic myelofibrosis (PIMF. Aim: Our primary aim was to find out the correlation between the JAK2V617F mutational status and the clinico-hematologic characteristics, as well as the international prognostic scoring system (IPSS scoring of patients with PIMF. Materials and Methods: Clinical and hematologic features were reviewed for 68 patients with primary idiopathic myelofibrosis (PIMF. JAK2V617F mutation status was analyzed by amplification refractory mutation screening-polymerase chain reaction. The patients were further stratified into low, intermediate-1, intermediate-2 and high-risk groups on the basis of IPSS scoring. Results: The JAK2V617F mutation was detected in 58.8% patients. Univariate analysis of variables at presentation identified that JAK2V617F negative patients were significantly associated with more severe anemia (P = 0.045, younger age (P = 0.008, higher transfusion requirement (P = 0.017, and thrombocytopenia (P = 0.015. Patients who were homozygous for JAK2V617F mutation were associated with thrombocytosis (P = 0.014 and also had higher median total leucocyte count (P = 0.20 than the other groups. No significant correlation was detected between JAK2V617F mutational status and the presence of constitutional symptoms, spleen size, grade of bone marrow fibrosis or prognostic risk stratification of the PIMF patients. Conclusion: The variations in the prognostic implication of PIMF patients with mutation status as stated by various publications worldwide, reinstates the need for larger prospective studies using standardized JAK2V617F quantification methods as well as estimation of other newer molecular markers to develop deeper insight into various molecular alterations involving PIMF patients in India as well as worldwide.

  16. Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Elisa K. [Department of Oncology, Saint John Regional Hospital, Saint John (Canada); Woods, Ryan; McBride, Mary L. [Cancer Control Research Department, BC Cancer Agency, Vancouver (Canada); Virani, Sean [Division of Cardiology, University of British Columbia, Vancouver (Canada); Nichol, Alan [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Speers, Caroline [Breast Cancer Outcomes Unit, BC Cancer Agency, Vancouver (Canada); Wai, Elaine S. [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca [Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada)

    2014-03-15

    Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast

  17. Néstor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations.

    Science.gov (United States)

    Cabanillas, Rubén; Cadiñanos, Juan; Villameytide, José A F; Pérez, Mercedes; Longo, Jesús; Richard, José M; Alvarez, Rebeca; Durán, Noelia S; Illán, Rafael; González, Daniel J; López-Otín, Carlos

    2011-11-01

    Progeria syndromes are rare disorders that involve premature aging. Mutations in BANF1 have been recently reported to cause a new hereditary progeroid syndrome that we now propose to call the Néstor-Guillermo progeria syndrome (NGPS). We describe herein the clinical features of the first two NGPS patients, who phenocopy features of classic progerias (i.e., Hutchinson-Gilford progeria syndrome or mandibuloacral dysplasia), such as aged appearance, growth retardation, decreased subcutaneous fat, thin limbs, and stiff joints. However, these NGPS patients have a distinctive phenotype. In their early adulthood (32 and 24 years of age), they have no signs of cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia. In contrast, they suffer profound skeletal abnormalities that affect their quality of life. The observed differences are of utmost importance to patients and their families and palliation of osseous manifestations is a priority, given their relatively long lifespan. We define NGPS as a chronic progeria because of its slow clinical course and relatively long survival, despite its early onset. Understanding the differences between progeria syndromes might contribute to the development of treatment strategies for common skeletal conditions, as well as aging itself.

  18. Epigenetic changes in myelofibrosis

    DEFF Research Database (Denmark)

    Myrtue Nielsen, Helene; Lykkegaard Andersen, Christen; Westman, Maj

    2017-01-01

    , in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation...

  19. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease.

    Science.gov (United States)

    Palmio, Johanna; Jonson, Per Harald; Evilä, Anni; Auranen, Mari; Straub, Volker; Bushby, Kate; Sarkozy, Anna; Kiuru-Enari, Sari; Sandell, Satu; Pihko, Helena; Hackman, Peter; Udd, Bjarne

    2015-11-01

    DNAJB6 is the causative gene for limb-girdle muscular dystrophy 1D (LGMD1D). Four different coding missense mutations, p.F89I, p.F93I, p.F93L, and p.P96R, have been reported in families from Europe, North America and Asia. The previously known mutations cause mainly adult-onset proximal muscle weakness with moderate progression and without respiratory involvement. A Finnish family and a British patient have been studied extensively due to a severe muscular dystrophy. The patients had childhood-onset LGMD, loss of ambulation in early adulthood and respiratory involvement; one patient died of respiratory failure aged 32. Two novel mutations, c.271T > A (p.F91I) and c.271T > C (p.F91L), in DNAJB6 were identified by whole exome sequencing as a cause of this severe form of LGMD1D. The results were confirmed by Sanger sequencing. The anti-aggregation effect of the mutant DNAJB6 was investigated in a filter-trap based system using transient transfection of mammalian cell lines and polyQ-huntingtin as a model for an aggregation-prone protein. Both novel mutant proteins show a significant loss of ability to prevent aggregation.

  20. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  1. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.

    Science.gov (United States)

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A; Sumikawa, Katumi

    2015-02-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.

  2. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

    Science.gov (United States)

    Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

    2014-12-04

    Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA.

    Directory of Open Access Journals (Sweden)

    Moritz F Sinner

    2010-07-01

    Full Text Available BACKGROUND: Early repolarization pattern (ERP on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg] comprised of individuals of Central-European descent. METHODS AND FINDINGS: Electrocardiograms of 1,945 participants aged 35-74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9 codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005. Age-stratified analyses showed hazard ratios (HRs for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05-3.68, p = 0.035 for both sexes and 2.65 (95% CI 1.21-5.83, p = 0.015 for men between 35-54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58-6.28, p = 0.001 for both sexes and to 4.27 (95% CI 1.90-9.61, p<0.001 for men between 35-54 y. HRs for all-cause mortality were weaker but reached significance. CONCLUSIONS: We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior

  4. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

    Science.gov (United States)

    Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

    2017-04-01

    The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  5. Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient.

    Science.gov (United States)

    Kawashima-Goto, Sachiko; Imamura, Toshihiko; Seki, Masafumi; Kato, Motohiro; Yoshida, Kenichi; Sugimoto, Atsuya; Kaneda, Daisuke; Fujiki, Atsushi; Miyachi, Mitsuru; Nakatani, Takuya; Osone, Shinya; Ishida, Hiroyuki; Taki, Tomohiko; Takita, Junko; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ogawa, Seishi; Hosoi, Hajime

    2015-04-01

    Investigation of genetic alterations associated with relapse in acute lymphoblastic leukemia (ALL) may help to identify druggable targets for specific therapies. Early T-cell precursor ALL (ETP-ALL) is a subtype of T-ALL with poor prognosis. Although the genetic landscape of ETP-ALL has been determined, genetic alterations related to the relapse of ETP-ALL have not been fully investigated. Here, we report the first patient with relapsed pediatric ETP-ALL to exhibit a homozygous JAK3 activating mutation, V674A, caused by acquired uniparental disomy (UPD). Single nucleotide polymorphism array analysis revealed acquired UPD (aUPD) at the 19p13.3-p12 locus only in leukemic cells at relapse. Sanger sequence of the JAK3 gene, which was located at 19p13.1 and frequently mutated in ETP-ALL, was performed in paired leukemic samples to determine homozygous JAK3 V674A mutation only in relapsed leukemic cells. In contrast, leukemic cells at initial diagnosis harbored hemizygous JAK3 V674A mutation. Further, whole-exome sequencing revealed mutations in 18 genes only in relapsed samples, although none of these was recurrent in T-ALL. These findings suggest that aUPD at 19p13.1 is partly associated with relapse in this patient. Pharmacological inhibition of JAK3 may be therapeutic in such cases.

  6. 儿童学习障碍原因及早期表现%Cause and early manifestation of children learning disabilities

    Institute of Scientific and Technical Information of China (English)

    苏萍; 周祖文

    2005-01-01

    personality obstacle and countersocial behaviors. Therefore, to review on the causes and early signs of child learning difficulties is important for finding the common reasons and main manifestations, and benefiting for the early diagnosis and interventions for children with learning disabilities.DATA SOURCES: Using the terms "Learning disabilities, Children, Survey documents", the relative articles published in the English from January 1985 to December 2003, were searched in PubMed database by computer.A search in China periodical database and Wanfang database was also conducted using the key word of "Learning disabilities, Children, review"for related articles published in Chinese from January 1990 to December 2003.STUYD SELECTION: Original articles were selected after elimination of the irrelative ones, inclusion criteria: randomized control study of the cause, early manifestations of children learning disability, as well as prognosis and correcting methods were selected.DATA EXTRACTION: Of the total 25 articles were about children learning disability, 16 were found closely related to be subjected and concerned and 9 were repetition ones.DATA SYNTHESIS: Totally 3 132 children with learning difficulties according to the diagnostic standards involved in the 16 experiments.And 2 081 children in 10 articles were investigated and revealed, the cause might involve heredity factors, brain dysfunction, brain structural abnormality, brain trauma and environment influence; 1 051 cases in 6 articles were analyzed and indicated that the main presentation of children learning disability consists of reading obstacle, spelling and writing difficulties, calculating obstacle, mood and behavior problems, moreover the prognosis and correcting methods were also mentioned.CONCLUSION: The cause of children learning disability is still unclear,it might be the combined results of multiple intrinsic and extrinsic factors,and divided into reading obstacle, spelling and writing difficulties

  7. Procalcitonin and C-reactive protein in early diagnosis of sepsis caused by either Gram-negative or Gram-positive bacteria.

    Science.gov (United States)

    Liu, H H; Zhang, M W; Guo, J B; Li, J; Su, L

    2017-02-01

    Sepsis is the most frequent cause of systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT) and C-reactive protein (CRP) are well-known predictors of sepsis. Serum PCT levels are associated with blood culture positivity in patients with sepsis, but the magnitude of elevation of PCT and CRP levels at the onset of sepsis is unknown in Gram-negative (GN) bacteremia and in Gram-positive (GP) bacteremia. To evaluate the PCT and CRP levels in 72 h at the onset of sepsis in GN and GP bacteremia. We retrospectively analyzed the data from 648 blood-positive specimens from three integrated teaching hospitals in Xiamen, China. One hundred and forty-seven adult patients with sepsis within 72 h enrolled in the study. Serum PCT and CRP level were assessed according GN or GP bacteremia. A total of 147 (22.68 %) patients were eligible for inclusion in the study, including 56 GP sepsis and 91 GN sepsis. PCT, but not CRP levels, was significantly higher in patients in the GP group than in the GN group (23.64 vs 6.18 ng/mL, p sepsis than GP sepsis in 72 h. There are not differences in CRP. The separation of PCT and CRP phenomenon is helpful for early diagnosis of GP sepsis.

  8. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations.

    Science.gov (United States)

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment.

  9. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations

    Directory of Open Access Journals (Sweden)

    Parisá Khodayar-Pardo

    2016-07-01

    Full Text Available Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment.

  10. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations

    Science.gov (United States)

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment. PMID:27504083

  11. New method for early detection of two random amplified polymorphic DNA (RAPD groups of Staphylococcus aureus causing bovine mastitis infection in Paraná State, Brazil

    Directory of Open Access Journals (Sweden)

    Dicezar Gonçalves

    2010-04-01

    Full Text Available The aim of this work was to develop a fast and accurate molecular approach to allow early detection of two RAPD groups of S. aureus causing bovine mastitis. Seventy five S. aureus isolates from infected animals were characterized by RAPD. Genomic fragments isolated from the unique bands present in either group were cloned and sequenced. Based on the DNA sequences, specific primers were designed to allow for the simultaneous detection of either group by multiplex PCR of S. aureus DNA isolated from clinical and subclinical bovine mastitis. Results showed that these proposed primers set could be used to detect various clinical and subclinical S. aureus isolates as well as the detection of the microorganism in bulk milk. Their use as a specific method for effective and early diagnostic tool for S. aureus infection in dairy herds is suggested.Esta pesquisa objetivou o desenvolvimento de técnica rápida e eficiente para diagnosticar precocemente diferentes linhagens de S. aureus causadoras de mastite bovina. Como resultados da metodologia empregada, foram isoladas duas linhagens destas bactérias que causam diferentes tipos de mastite bovina. Os fragmentos de DNA genômico caracterizando ambas as linhagens, por meio de RAPD foram inseridos em vetor plasmidial pGEM e clonados por meio de clones T10 F1 de Escherichia coli. As seqüências obtidas permitiram desenhar iniciadores específicos para o reconhecimento de ambas as linhagens, os quais foram testados com amostras de S. aureus e com outras linhagens próximas. O diagnóstico por meios moleculares, pode ser realizado diretamente de amostras coletadas de rebanhos leiteiros assim como dos equipamentos de ordenha. A significância deste estudo consiste em um rápido e acurado método para localizar animais infectados, representando importante ferramenta no manejo do rebanho, na redução de custos com tratamentos e, rápida recuperação de rebanhos infectados.

  12. REDUCED INTENSITY HEMATOPOIETIC CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY MYELOFIBROSIS: A COHORT ANALYSIS FROM THE CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH

    Science.gov (United States)

    Gupta, Vikas; Malone, Adriana K.; Hari, Parameswaran N.; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K.; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T.; Waller, Edmund K.; Costa, Luciano J.; Antin, Joseph H.; Kamble, Rammurti T.; van Besien, Koen M.; Savani, Bipin N.; Schouten, Harry C.; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J.; Wirk, Baldeep; Aljurf, Mahmoud D.; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R.; Norkin, Maxim; Lewis, Ian D.; Hale, Gregory A.; Woolfrey, Ann E.; Miller, Alan M.; Ustun, Celalettin; Jagasia, Madan H.; Lill, Michael; Maziarz, Richard T.; Cortes, Jorge; Kalaycio, Matt E.; Saber, Wael

    2014-01-01

    We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients. RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients. PMID:24161923

  13. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis

    Science.gov (United States)

    Seymour, John F.; Roberts, Andrew W.; Wadleigh, Martha; To, L. Bik; Scherber, Robyn; Turba, Elyce; Dorr, Andrew; Zhu, Joy; Wang, Lixia; Granston, Tanya; Campbell, Mary S.; Mesa, Ruben A.

    2015-01-01

    Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 109/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT00745550. PMID:25762180

  14. Translocation t(3;12(q26;q21 In Jak2V617F Point Mutation Negative Chronic Idiopathic Myelofibrosis: A Case Report

    Directory of Open Access Journals (Sweden)

    S. Mešanović

    2014-06-01

    Full Text Available The myeloproliferative diseases (MPDs or myelo-proliferative neoplasms (MPNs are a group of diseases of the bone marrow in which excess cells are produced. Chronic idiopathic myelofibrosis (CIMF is a stem cell defect characterized by splenomegaly with multiorgan extramedullary hematopoiesis, immature peripheral blood granulocytes and erythrocytes and progressive bone marrow fibrosis. The most common chromosomal abnormalities seen in CIMF patients include numerical changes of chromosomes 7, 8 and 9, and structural changes of 1q, 5q, 13q and 20q. At least 75.0% of patients with bone marrow abnormalities have one or more of these chromosomal anomalies. Detection of the Janus kinase 2 (JAK2 mutation may be a potential major breakthrough for understanding the pathobiology of MPNs, and is an essential part of the diagnostic algorithm. In this study, we describe a JAK2V617F mutation negative CIMF patient who has the chromosomal translocation t(3;12(q26;q21 in her karyotype.

  15. Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality.

    Directory of Open Access Journals (Sweden)

    Paula Dietrich

    Full Text Available Familial Dysautonomia (FD is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function.

  16. Manifestations and causes of psychological and behavioral problems in infant patients and patients of early age%婴幼儿患者的心理行为问题表现及成因

    Institute of Scientific and Technical Information of China (English)

    饶红

    2002-01-01

    @@ Large amounts clinical facts demonstrate that many diseases can induce emotional disturbances and psychological problems such as fear, anxiety, restlessness, agitation and irritability in infantile patients and patients of early age.The author would like to discuss briefly several common psychological and behavioral problems and the corresponding causes of them.

  17. 早期成人破伤风首诊误诊原因分析%Primal Misdiagnosis Causes of 12 Adult Patients with Tetanus in Early Period

    Institute of Scientific and Technical Information of China (English)

    方尔斌

    2014-01-01

    目的:分析成人破伤风的早期临床表现,总结破伤风误诊原因,以提高首诊准确率。方法回顾性分析我院12例首诊误诊的成人破伤风的临床资料。结果12例均有不同程度张口困难及面肌痉挛表现,首诊时均未提供明确外伤史和慢性感染窦道史,分别于我院普外科、感染科、急诊科、神经内科、骨科及口腔科首诊,诊断抽搐原因待查4例,误诊为颈椎病2例,腰椎病、多颅神经炎、药物锥体外系反应、面神经炎、脑梗死及颞下颌关节炎各1例。12例均结合病史及临床表现确诊为破伤风,予相应治疗皆痊愈。随访1年无明显后遗症。结论首诊时无明确外伤史及典型破伤风表现的早期成人破伤风患者容易漏误诊。临床遇到面肌痉挛及张口困难表现者,尤其是1978年前出生未接种过百白破疫苗者,应高度警惕破伤风。%Objective To analyze clinical manifestations of adult tetanus in early period,and summarize the misdiag-nosis causes in order to improve accuracy of the primal diagnosis. Methods Clinical data of 12 adult patients with tetanus misdiagnosed in the primal diagnosis in our hospital was retrospectively analyzed. Results All the 12 patients had difficulties opening mouths and facial spasms in different degrees,while clear histories of trauma and chronic sinus infection were not of-fered in the first diagnosis. The patients were misdiagnosed as having convulsions of unknown origin(4 cases),cervical spon-dylosis(2 cases),lumbar spondylosis(1 case),brain neuritis(1 case),drug-induced extrapyramidal reactions(1 case), facial neuritis(1 case),cerebral infarction(1 case)and temporomandibular arthritis(1 case)in departments of general sur-gery,infectious diseases,emergency,neurology,orthopedics and dentistry respectively in the primal diagnosis. All the 12 pa-tients were confirmed of the diagnosis of tetanus after being combined with history and clinical

  18. DNA methylation profiling of sorted cells from myelofibrosis patients reveals aberrant epigenetic regulation of immune pathways and identifies early MPN driver genes

    DEFF Research Database (Denmark)

    Nielsen, H. M.; Andersen, C. L.; Kristensen, L. S.;

    2015-01-01

    Methylation 450K BeadChip. Candidate genes were validated by pyrosequencing in a second cohort of 30 MF patients where DNA was extracted from full blood (PB). To identify potential driver genes, the DNA methylation status of candidate genes was likewise analyzed in PB from a larger cohort consisting of 60 ET...

  19. Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two year results of a randomised controlled trial

    OpenAIRE

    Peul, Wilco; Hout, Wilbert; Brand, René; Thomeer, Raph; Koes, Bart

    2008-01-01

    Objectives: To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. Design: Randomised controlled trial. Setting: Nine Dutch hospitals. Participants: 283 patients with 6-12 weeks of sciatica. Interventions: Early surgery or an intended six months of continued conservative treatment, with delayed surgery if needed. Main outcome measures: Scores from Roland disability questionnaire for sciatica, visua...

  20. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research.

    Science.gov (United States)

    Gupta, Vikas; Malone, Adriana K; Hari, Parameswaran N; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T; Waller, Edmund K; Costa, Luciano J; Antin, Joseph H; Kamble, Rammurti T; van Besien, Koen M; Savani, Bipin N; Schouten, Harry C; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J; Wirk, Baldeep; Aljurf, Mahmoud D; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R; Norkin, Maxim; Lewis, Ian D; Hale, Gregory A; Woolfrey, Ann E; Miller, Alan M; Ustun, Celalettin; Jagasia, Madan H; Lill, Michael; Maziarz, Richard T; Cortes, Jorge; Kalaycio, Matt E; Saber, Wael

    2014-01-01

    We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    Yao-hua KE; Hua YUE; Jin-wei HE; Yu-juan LIU; Zhen-lin ZHANG

    2009-01-01

    Aim: A previous study showed that individuals of Japanese descent affected by early onset familial Paget's disease of bone (PDB) car-ried a 27-bp duplication at position 75 (75dup27) in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation (78dup27) in exon 1 of TNFRSF11A in a Chinese family with early onset PDB. Methods: We conducted clinical and genetic studies in a non-consanguineous Chinese family with early onset PDB. The entire coding region of TNFRSF11A was amplified and directly sequenced directly.Results: A novel 27-bp duplication in exon 1 (78dup27) in TNFRSF11A was found in four affected individuals and one asymptomatic individual. Although this duplication was the same length as the previously identified mutation (27 bp, from bases 78 to 104), in our patients the nine duplicated amino acids in the RANK signal peptide were LLLLCALLA. The phenotypes of affected individuals in this family overlapped with both early onset PDB and classic PDB, but several distinguishing features were found in our patients. The key difference between our familial PDB and the Japanese early onset PDB was the age of onset, which in most of our patients was during their late 20s (except for the propositus' niece). Another notable difference was that the propositus' son (24 years old), who carried the 78dup27 mutation, had no clinical symptoms or bone abnormalities, except for increased serum ALP, OC and CTX.Conclusion: Our findings may provide a better understanding of the clinical features of early onset PDB and support the notion of a hot spot for mutations in exon 1 of the TNFRSF11A gene.

  2. [The place of JAK2 inhibitors in the treatment of myelofibrosis. An amendment to the recommendations for diagnosis and treatment of Ph negative myeloproliferations of the Czech group for Ph- myeloproliferative disorders (CZEMP)].

    Science.gov (United States)

    Červinek, Libor; Doubek, Michael; Penka, Miroslav; Schwarz, Jiří

    2014-02-01

    Primary myelofibrosis (PMF) belongs to Ph- myeloproliferative diseases. The only curative treatment is hematopoietic stem cell transplantation (HSCT). Conservative treatment options comprise supportive care, especially administration of red blood cell and platelet transfusions, and medication. Hydroxyurea, interferon α, anagrelide, corticosteroids, androgens, or inhibitors of angiogenesis (thalidomide, lenalidomide, pomalidomide) may be used for treatment of PMF, depending on the clinical stage and disease symptoms present. Also splenectomy or radiotherapy of enlarged spleen have palliative potential. JAK2 kinase inhibitors represent a novel class of drugs with a very dynamic development. Ruxolitinib, an oral selective inhibitor of JAK1 and JAK2 kinases, has shown high efficacy in patients with high-risk PMF (or with myelofibrosis following polycythemia vera or essential thrombocythemia) to ameliorate disease symptoms and to reduce splenomegaly in randomized trials COMFORT-I and COMFORT-II. Long-term monitoring of the enrolled patients demonstated prolongation of overall survival. The drug is well-tolerated, the most common side effects of treatment with ruxolitinib being deepening of thrombocytopenia and temporary worsening of anemia. The current review deals with the place of JAK2 inhibitors (and the only drug already approved for clinical use - ruxolitinib) in the management of PMF, as an addendum to the Summary of recommendations for the diagnosis and therapy of BCR/ABL-negative myeloproliferations of the Czech Hematological Societys CZEMP.

  3. Fitotoxicidade causada por herbicidas na fase inicial de desenvolvimento da cultura do sorgo Phytotoxicity caused by herbicides to sorghum crop at early stages of development

    Directory of Open Access Journals (Sweden)

    P.C. Magalhães

    2000-01-01

    ículas e de grãos. Os tratamentos que proporcionaram os mais altos rendimentos foram: paraquat + espalhante adesivo, ametryn + óleo mineral, retirada mecânica de folhas e cyanazine + simazine aplicados no estádio de 6 folhas. À exceção do tratamento cyanazine + simazine aplicado no estádio de 4 folhas, o uso de herbicidas em pós-emergência inicial e área total na cultura do sorgo mostrou-se seletiva . Mesmo quando houve injúrias, decorrentes da ação dos herbicidas, elas não foram suficientes para prejudicar a produção. O bom controle das plantas daninhas proveniente do uso dos herbicidas possibilitou ao sorgo expressar melhor seu potencial produtivo.The application of herbicides in early broadcast postemergence and band directed of herbicides in sorghum has raised considerably with increasing planting acreage in Brazil. However, these products can cause phytoxicity since they are not completely selective to the crop. Since these herbicides basically block metabolic processes in the plants, one questions what effects these injuries will have on grain yield. Therefore, the objective of this research was to study the phytotoxic effect caused by the application of herbicides on the crop, at the initial phase and at late postemergence in directed spray, as well as on sorghum grain yield. This study was carried out during the growing season of 1994/95 and 1995/96, using the hybrid BR 700, in a complete randomized block design, with 12 treatments and four replications. The treatments consisted of the combination of the following herbicides at several rates: cyanazine + simazine with or without mineral oil, applied at the 4-and-6 leaf growth stages; paraquat + adjuvant and ametryn + mineral oil, applied as directed spray at the 12-leaf growth stage. The control treatments were weed free and weeded plus mechanical defoliation of the first, second and third pair of sorghum leaves at the 12-leaf stage. Leaf area, plant dry weight, leaf chlorophyll content, plant

  4. Early Stress Causes Sex-Specific, Life-Long Changes in Behaviour, Levels of Gonadal Hormones, and Gene Expression in Chickens

    NARCIS (Netherlands)

    Elfwing, Magnus; Natt, Daniel; Goerlich - Jansson, Vivian|info:eu-repo/dai/nl/321975502; Persson, Mia; Hjelm, Jonas; Jensen, Per

    2015-01-01

    Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of

  5. Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation : two year results of a randomised controlled trial

    NARCIS (Netherlands)

    Peul, W.C.; Hout, van den W.B.; Brand, R.; Thomeer, R.T.W.M.; Koes, B.W.

    2008-01-01

    Objectives: To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. Design: Randomised controlled trial. Setting: Nine Dutch hospitals. Participants: 283 patients with 6-12 weeks of sciatica. Interventions

  6. IQ in late adolescence/early adulthood, risk factors in middle age and later all-cause mortality in men: the Vietnam Experience Study

    DEFF Research Database (Denmark)

    Batty, G D; Shipley, M J; Mortensen, L H;

    2008-01-01

    OBJECTIVE: To examine the role of potential mediating factors in explaining the IQ-mortality relation. DESIGN, SETTING AND PARTICIPANTS: A total of 4316 male former Vietnam-era US army personnel with IQ test results at entry into the service in late adolescence/early adulthood in the 1960/1970s (...

  7. Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: Two year results of a randomised controlled trial

    NARCIS (Netherlands)

    W.C. Peul (Wilco); W.B. van den Hout (Wilbert); R. Brand (René); R.T.W.M. Thomeer (Raph); B.W. Koes (Bart)

    2008-01-01

    textabstractObjectives: To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. Design: Randomised controlled trial. Setting: Nine Dutch hospitals. Participants: 283 patients with 6-12 weeks of sciatica. I

  8. Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two year results of a randomised controlled trial.

    NARCIS (Netherlands)

    Peul, W.C.; Hout, W.B. van den; Brand, R.; Thomeer, R.T.; Koes, B.W.; Eekhof, J.A.H.; Tans, J.T.; Houwelingen, H.C. van; Nuyten, M.; Bergman, P.; Holtkamp, G.; Dukker, S.; Mast, A.; Smakman, L.; Waanders, C.; Polak, P.; Nieborg, A.; Walchenbach, R.; Rossum, J. van; Schutte, P.J.; Verheul, G.A.; Dalman, J.A.; Wurzer, J.A.; Sven, J.W.; Kloet, A.; Merkies, I.S.; Dulken, H. van; Lambrechts, P.C.; Keunen, R.W.; Hoffmann, C.; Haan, J.; Groen, R.; Kuiters, R.R.; Roos, R.A.C.; Voormolen, J.H.

    2008-01-01

    OBJECTIVES: To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. DESIGN: Randomised controlled trial. SETTING: Nine Dutch hospitals. PARTICIPANTS: 283 patients with 6-12 weeks of sciatica. INTERVENTIONS

  9. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy

    NARCIS (Netherlands)

    Smets, Katrien; Duarri, Anna; Deconinck, Tine; Ceulemans, Berten; van de Warrenburg, Bart P.; Zuechner, Stephan; Gonzalez, Michael Anthony; Schuele, Rebecca; Synofzik, Matthis; Van der Aa, Nathalie; De Jonghe, Peter; Verbeek, Dineke S.; Baets, Jonathan

    2015-01-01

    Background: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. Methods: Whole exome sequencing in a cerebellar ataxia

  10. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy

    NARCIS (Netherlands)

    Smets, K.; Duarri, A.; Deconinck, T.; Ceulemans, B.; Warrenburg, B.P.C. van de; Zuchner, S.; Gonzalez, M.A.; Schule, R.; Synofzik, M.; Aa, N. van der; Jonghe, P. De; Verbeek, D.S.; Baets, J.

    2015-01-01

    BACKGROUND: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. METHODS: Whole exome sequencing in a cerebellar ataxia

  11. Early Stress Causes Sex-Specific, Life-Long Changes in Behaviour, Levels of Gonadal Hormones, and Gene Expression in Chickens

    NARCIS (Netherlands)

    Elfwing, Magnus; Natt, Daniel; Goerlich - Jansson, Vivian; Persson, Mia; Hjelm, Jonas; Jensen, Per

    2015-01-01

    Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of s

  12. Urgent endarterectomy using pretreatment with free radical scavenger, edaravone, and early clamping of the parent arteries for cervical carotid artery stenosis with crescendo transient ischemic attacks caused by mobile thrombus and hemodynamic cerebral ischemia. Case report.

    Science.gov (United States)

    Kobayashi, Masakazu; Ogasawara, Kuniaki; Inoue, Takashi; Saito, Hideo; Komoribayashi, Nobukazu; Suga, Yasunori; Ogawa, Akira

    2007-03-01

    A 68-year-old man with left cervical internal carotid artery stenosis suffered crescendo transient ischemic attacks caused by mobile thrombus detected by carotid echography and secondary impairment of cerebral hemodynamic reserve demonstrated by positron emission tomography. Urgent carotid endarterectomy (CEA) was performed following pretreatment with edaravone and early clamping of the carotid arteries without intraluminal shunting. The postoperative course was uneventful, and postoperative magnetic resonance imaging and single-photon emission computed tomography revealed no new cerebral ischemic lesions and no findings of cerebral hyperperfusion, respectively. The risks associated with CEA are higher for patients with evolving stroke or crescendo transient ischemic attacks than that for patients with stable disease. This case demonstrates that urgent endarterectomy for cervical carotid artery stenosis with crescendo transient ischemic attacks caused by mobile thrombi and hemodynamic cerebral ischemia can be successfully performed following pretreatment with edaravone and early clamping of the carotid arteries.

  13. Jiancheng special-purpose vehicle clutch causes and prevention of early damage%建成专用车离合器早期损坏原因及预防

    Institute of Scientific and Technical Information of China (English)

    赵小柏; 李超前

    2011-01-01

    By analysis of the causes of clutch's early damage in special transport vehicle for explosive equipments and materials of Harbin Jiancheng series,the authors put forward preventive measures.%分析了哈尔滨建成系列民爆器材运输专用车在使用中出现离合器早期损坏的原因,提出了预防措施。

  14. 骨髓纤维化患者TGF-β1及其Ⅰ、Ⅱ型受体测定的临床意义%Clinical significance of TGF-β1, TGFR l and TGFR 2 determination in patients with myelofibrosis

    Institute of Scientific and Technical Information of China (English)

    陈晓莉; 史占忠; 蒲晓允; 邓均

    2001-01-01

    Objective To investigate the significance of TGF-β1, TGFRl and TGFR2 in the pathogenesis and prognosis in patients with myelofibrosis. Methods The expression of TGF-β1 and its receptors (TGFR1 and TGFR2 ) in bone marrow tissues and the level of TGF-β1 in the blood of 23 patients with myelofibrosis were detected by SABC immunocytochemistry and ELISA repectively. Results Expression of TGF-β1 and TGFR 1 was significantly higher in primary and secondary myelofibrosis patients than that of the control. No significant difference of TGFR2 expression was found between the groups of myelofibrosis and the control (P>0.05). The level of TGF-β1 in the blood of the patients with myelofibrosis was significantly higher than that of the control (P0.05)。骨髓纤维化患者血清TGF-β1水平明显高于对照组,差异非常显著(P<0.01),继发性骨髓纤维化患者升高更明显,骨髓纤维化临床缓解后血清TGF-β1水平下降至接近正常。结论 TGF-β1及其 Ⅰ、Ⅱ 型受体参与骨髓纤维化的发生,骨髓纤维化患者TGF-β1、TGFR1的检测有助于判断其预后。

  15. Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats.

    Science.gov (United States)

    Ishida, Akimasa; Tamakoshi, Keigo; Hamakawa, Michiru; Shimada, Haruka; Nakashima, Hiroki; Masuda, Tadashi; Hida, Hideki; Ishida, Kazuto

    2011-11-20

    Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage. Rats were subjected to ICH via low-dose collagenase infusion or sham stroke. One day after surgery, the ipsilateral forelimbs of half of the ICH and sham rats were casted for a week to induce the use of their contralateral forelimbs. Behavioral assessments were performed on days 10-12 and 26-28 after the surgery and followed by histological assessments. Improvements in skilled reaching and coordinated stepping function were found in the FLU-treated group in comparison with the untreated group after ICH. Additionally, FLU-treated ICH animals showed more normal and precise reaching and stepping movements as compared with ICH control animals. In contrast, FLU did not have a significant impact on gross sensory-motor functions such as the motor deficit score, contact placing response and spontaneous usage of the impaired paw. The volume of tissue lost and the number of spared corticospinal neurons in lesioned motor cortex were not affected by early FLU after ICH. These findings demonstrate the efficacy of early focused use of an impaired limb after internal capsule hemorrhage.

  16. Extramedullary pulmonary hematopoiesis causing pulmonary hypertension and severe tricuspid regurgitation detected by {sup 99m} technetium sulfur colloid bone marrow scan and single-photon emission computed tomography/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian [Dept. of Diagnostic Radiology, Khoo Teck Puat Hospital, Singapore (Singapore)

    2014-06-15

    Extramedullary pulmonary hematopoiesis is a rare entity with a limited number of case reports in the available literature only. We report the case of a 66-year-old man with known primary myelofibrosis, in whom a {sup 99m}technetium sulfur colloid bone marrow scan with single-photon emission computed tomography (SPECT)/CT revealed a pulmonary hematopoiesis as the cause of pulmonary hypertension and severe tricuspid regurgitation. To the best of our knowledge, this is the first description of {sup 99m} technetium sulfur colloid SPECT/CT imaging in this rare condition.

  17. Early mortality and primary causes of death in mothers of children with intellectual disability or autism spectrum disorder: a retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Jenny Fairthorne

    Full Text Available INTRODUCTION: Mothers of children with intellectual disability or autism spectrum disorder (ASD have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. METHODS: The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. RESULTS AND DISCUSSION: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. CONCLUSION: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity.

  18. Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies

    Directory of Open Access Journals (Sweden)

    Srdan Verstovsek

    2016-12-01

    Full Text Available Abstract Background Pacritinib (SB1518 is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD, safety, and clinical activity of pacritinib in patients with myelofibrosis (MF and other advanced myeloid malignancies. Methods In the phase 1 dose-escalation part of the study, 43 adults with advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD. In the phase 2 part of the study, 31 adults with refractory or intermediate- or high-risk newly diagnosed MF and any degree of cytopenia received pacritinib 400 mg QD. The primary endpoint is a ≥35% reduction in spleen volume at week 24 as determined by magnetic resonance imaging. Results Five patients (11.6% experienced a dose-limiting toxicity during cycle 1 of phase 1. The clinical benefit rate was 86.0% (13 patients achieving clinical improvement and 24 patients having stable disease. The MTD was established at 500 mg QD, and the recommended phase 2 dose was 400 mg QD. In phase 2, the primary endpoint was achieved by 23.5% of evaluable patients (4/17, with 47.4% (9/19 achieving a ≥50% spleen length reduction at week 24 as measured by physical examination. At week 24, 38.9% of evaluable patients (7/18 achieved a ≥50% decrease in MF Quality of Life and Symptom Assessment total score. Gastrointestinal toxicities were the most common adverse events and were predominantly grade 1/2 in severity. Grade 3/4 anemia was reported in 5/31 patients and grade 3/4 thrombocytopenia was reported in 3/31 patients. The most frequent AEs considered to be treatment related were diarrhea (28/31, nausea (15/31, vomiting (9/31, and fatigue (4/31. Grade 3 treatment-related AEs were reported in seven patients (22.6%, four of whom had diarrhea. No grade 4/5 treatment-related AEs were reported. No leukopenia, neutropenia, or lymphopenia were reported. Conclusions Pacritinib was well

  19. Small RNA Sequencing Uncovers New miRNAs and moRNAs Differentially Expressed in Normal and Primary Myelofibrosis CD34+ Cells.

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    Paola Guglielmelli

    Full Text Available Myeloproliferative neoplasms (MPN are chronic myeloid cancers thought to arise at the level of CD34+ hematopoietic stem/progenitor cells. They include essential thrombocythemia (ET, polycythemia vera (PV and primary myelofibrosis (PMF. All can progress to acute leukemia, but PMF carries the worst prognosis. Increasing evidences indicate that deregulation of microRNAs (miRNAs might plays an important role in hematologic malignancies, including MPN. To attain deeper knowledge of short RNAs (sRNAs expression pattern in CD34+ cells and of their possible role in mediating post-transcriptional regulation in PMF, we sequenced with Illumina HiSeq2000 technology CD34+ cells from healthy subjects and PMF patients. We detected the expression of 784 known miRNAs, with a prevalence of miRNA up-regulation in PMF samples, and discovered 34 new miRNAs and 99 new miRNA-offset RNAs (moRNAs, in CD34+ cells. Thirty-seven small RNAs were differentially expressed in PMF patients compared with healthy subjects, according to microRNA sequencing data. Five miRNAs (miR-10b-5p, miR-19b-3p, miR-29a-3p, miR-379-5p, and miR-543 were deregulated also in PMF granulocytes. Moreover, 3'-moR-128-2 resulted consistently downregulated in PMF according to RNA-seq and qRT-PCR data both in CD34+ cells and granulocytes. Target predictions of these validated small RNAs de-regulated in PMF and functional enrichment analyses highlighted many interesting pathways involved in tumor development and progression, such as signaling by FGFR and DAP12 and Oncogene Induced Senescence. As a whole, data obtained in this study deepened the knowledge of miRNAs and moRNAs altered expression in PMF CD34+ cells and allowed to identify and validate a specific small RNA profile that distinguishes PMF granulocytes from those of normal subjects. We thus provided new information regarding the possible role of miRNAs and, specifically, of new moRNAs in this disease.

  20. NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.

    Science.gov (United States)

    Berciano, José; Peeters, Kristien; García, Antonio; López-Alburquerque, Tomás; Gallardo, Elena; Hernández-Fabián, Arantxa; Pelayo-Negro, Ana L; De Vriendt, Els; Infante, Jon; Jordanova, Albena

    2016-02-01

    The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. By then, a working diagnosis of sporadic early onset cerebellar ataxia with peripheral neuropathy was established. Screening of mutations associated with SCA and autosomal recessive cerebellar ataxias was negative. Her son showed a mild phenotype characterized by delayed motor milestones, and lower-limb hypotonia and areflexia. Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.

  1. Suicide and Other-Cause Mortality after Early Exposure to Smoking and Second Hand Smoking: A 12-Year Population-Based Follow-Up Study.

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    Vincent Chin-Hung Chen

    Full Text Available The association between smoking and suicide is still controversial, particular for early life cigarette smoking exposure. Few studies have investigated this association in adolescents using population-based cohorts, and the relationship with second hand smoking (SHS exposure has not been addressed.In this study, we followed a large population-based sample of younger people to investigate the association between smoking, SHS exposure and suicide mortality. Between October 1995 and June 1996, 162,682 junior high school students ages 11 to 16 years old living in a geographic catchment area in Taiwan were enrolled and then followed till December 2007 (1,948,432 person-years through linkage to the National Death Certification System. Participants who were currently smoking at baseline had a greater than six-fold higher suicide mortality than those who did not smoke (29.5 vs. 4.8 per 100,000 person-years, p20 cigarettes/per day. The estimated depression-adjusted odds ratio did not change substantially. The population attributable fractions for suicide associated with smoking and heavy SHS exposure (>20 cigarettes/per day were 9.6% and 10.6%, respectively.This study showed evidence of excess suicide mortality among young adults exposed to active or passive early life cigarette smoking.

  2. Relation between early life socioeconomic position and all cause mortality in two generations. A longitudinal study of Danish men born in 1953 and their parents

    DEFF Research Database (Denmark)

    Osler, Merete; Andersen, Anne-Marie Nybo; Batty, G David;

    2005-01-01

    OBJECTIVE: To examine (1) the relation between parental socioeconomic position and all cause mortality in two generations, (2) the relative importance of mother's educational status and father's occupational status on offspring mortality, and (3) the effect of factors in the family environment...... triads of father, mother, and offspring constituted of the cohort of men born in 1953, their parents, and grandparents. The educational status of mothers showed no independent effect on total mortality when father's occupational social class was included in the model in either of the triads. Low material...... wealth was the indicator that remained significantly associated with adult all cause mortality in a model also including parental social position and the intellectual climate of the family in 1968. In the men born in 1953 the influence of material wealth was strongest for deaths later in adult life...

  3. Choriodecidual inflammatory syndrome (CoDIS) is the leading, and under recognised, cause of early preterm delivery and second trimester miscarriage.

    Science.gov (United States)

    Sebire, N J

    2001-04-01

    Severe preterm birth (delivery before 32 completed weeks of gestation), with or without preterm premature rupture of the membranes (PPROM), remains the leading cause of perinatal mortality. It is proposed that localized inflammation of the chorion and decidua in the membranes immediately above the internal cervical os, with or without amniotic cavity infection and inflammation, is the leading, but under recognised, cause of second trimester miscarriage and severe preterm delivery. The term 'CoDIS' (choriodecidual inflammatory syndrome), may provide a better understanding of the underlying pathophysiology than currently used terminology which over emphasizes the importance of overt intra-amniotic infection as opposed to localized extra-amniotic inflammation which stimulates uterine evacuation.

  4. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations

    OpenAIRE

    Parisá Khodayar-Pardo; Andrés Peña Aldea; Ana Ramírez González; Adela Meseguer Carrascosa; Cristina Calabuig Bayo

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous ...

  5. Early Detection of Lightning Caused Wildfires and Prediction of Wildfire Behavior through Energy Distribution, Atmospherics, Geophysics, the Sun's Azimuth, and Topology

    Science.gov (United States)

    Giesige, C.; Nava, E.

    2016-12-01

    In the midst of a changing climate we have seen extremes in weather events: lightning, wildfires, hurricanes, tornadoes, and earthquakes. All of these ride on an imbalance of magnetic and electrical distribution about the earth including what goes on from the atmospheric and geophysic levels. There is relevance to the important role the sun plays in developing and feeding of the extreme weather events along with the sun's role helping to create a separation of charges on earth furthering climactic extremes. Focusing attention in North America and on how the sun, atmospheric and geophysic winds come together producing lightning events, there are connections between energy distribution in the environment, lightning caused wildfires, and extreme wildfire behavior. Lightning caused wildfires and extreme fire behavior have become enhanced with the changing climate conditions. Even with strong developments in wildfire science, there remains a lack in full understanding of connections that create a lightning caused wildfire event and lack of monitoring advancements in predicting extreme fire behavior. Several connections have been made in our research allowing us to connect multiple facets of the environment in regards to electric and magnetic influences on wildfires. Among them include: irradiance, winds, pressure systems, humidity, and topology. The connections can be made to develop better detection systems of wildfires, establish with more accuracy areas of highest risk for wildfire and extreme wildfire behavior, and prediction of wildfire behavior. A platform found within the environment can also lead to further understanding and monitoring of other extreme weather events in the future.

  6. Evaluation Of Factors Influencing On Causes Of Prosthetic Valve Re-operation And Early Postoperative Survival Tehran Emam hospital (1991-2001

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    Rahmani Reaza

    2003-06-01

    Full Text Available Prosthetic valve re-operation has greater mortality and morbidity than primary valve replacement. By recognition of factors influencing on causes of redo operation and preoperative survival, one can select appropriate prosthesis at primary valve replacement and when operation performed at appropriate time, surgical risk can be reduced."nMethods and Materials: Two hundred patients that underwent prosthetic valve re-operation from October 1991 through November 2001 were included in this study. There were 68 men and 132 women with the mean age of 42:tl 1.8 years. Structural failure was the commonest cause of bio-prosthesis replacement (93%. Valve thrombosis was the common cause of mechanical valve replacement (32%. Age younger Than 50 (P= 0.01 and interval after the first implantation more than 10 years (P= 0.01 affected bio-prosthesis degeneration."nResults: Atrial fibrillation (P<0.01, Older age especially more than 40 (P<0.05 and mitral position (P<0.01 affected mechanical valve thrombosis. Cross clamp time (P= 0.005, Tricuspid insufficiency (P = 0.001, NYHA IV (P = 0.005 and emergent operation (P= 0.001 were independent determinants of hospital mortality."nConclusion: In conclusion, in patients with more than 10-years life expectancy and age younger than 50, mechanical valve can be selected for primary valve replacement. If operation performed before patients reach deteriorated condition, preoperative survival would be excellent.

  7. Evolution, Abundance and Biocalcification of Calcareous Nannoplankton During the Aptian (Early Cretaceous): Causes and Consequences for C Isotopic Anomalies, Climate Changes and the Carbon Cycle.

    Science.gov (United States)

    Erba, E.

    2005-12-01

    The mid Cretaceous is marked by extreme greenhouse conditions, coeval with emplacement of large igneous provinces, C isotopic anomalies, major changes in structure and composition of the oceans, and accelerated rates in the evolutionary history of calcareous plankton. The Aptian is a crucial interval to decipher links between biotic evolution and environmental pressure: it is appealing for understanding nannofloral biocalcification and feedbacks in the carbonate system and in the global carbon cycle. Ontong Java, Manihiki and Kerguelen Plateaus formed in the Aptian affecting the ocean-atmosphere system with excess CO2, changes in Ca2+ and Mg2+ concentrations, and varying nutrient cycling. Two large C isotopic anomalies are associated with episodes of prolonged high primary productivity, changes in alkality, global warming and cooling, anoxia, speciations and extinctions in planktonic communities. Nannofossil diversity, abundance and biocalcification are quantified in continuous, complete, pelagic sections to derive biosphere-geosphere interactions at short and long time scales. The early Aptian C isotopic anomaly interrupts a speciation episode in calcareous nannoplankton paralleled by a drastic reduction in nannofossil paleofluxes culminating in the nannoconid crisis preceding the Oceanic Anoxic Event 1a and the negative C isotopic spike linked to clathrate melting presumably triggered by the thermal maximum at the onset of the mid Cretaceous greenhouse climate. No extinctions are recorded. In the early late Aptian resumption of nannoconid production and appearance of several taxa are coeval with a return to normal C isotopic values. The occurrence of calpionellids and diversified planktonic foraminifers indicate successful biocalcification and restoration of the thermocline. In the late Aptian a drop in nannofossil abundance and accelerated extinction rates are associated with another C isotopic excursion under cool conditions possibly due to a prolonged volcanic

  8. Heat waves imposed during early pod development in soybean (Glycine max) cause significant yield loss despite a rapid recovery from oxidative stress.

    Science.gov (United States)

    Siebers, Matthew H; Yendrek, Craig R; Drag, David; Locke, Anna M; Rios Acosta, Lorena; Leakey, Andrew D B; Ainsworth, Elizabeth A; Bernacchi, Carl J; Ort, Donald R

    2015-08-01

    Heat waves already have a large impact on crops and are predicted to become more intense and more frequent in the future. In this study, heat waves were imposed on soybean using infrared heating technology in a fully open-air field experiment. Five separate heat waves were applied to field-grown soybean (Glycine max) in central Illinois, three in 2010 and two in 2011. Thirty years of historical weather data from Illinois were analyzed to determine the length and intensity of a regionally realistic heat wave resulting in experimental heat wave treatments during which day and night canopy temperatures were elevated 6 °C above ambient for 3 days. Heat waves were applied during early or late reproductive stages to determine whether and when heat waves had an impact on carbon metabolism and seed yield. By the third day of each heat wave, net photosynthesis (A), specific leaf weight (SLW), and leaf total nonstructural carbohydrate concentration (TNC) were decreased, while leaf oxidative stress was increased. However, A, SLW, TNC, and measures of oxidative stress were no different than the control ca. 12 h after the heat waves ended, indicating rapid physiological recovery from the high-temperature stress. That end of season seed yield was reduced (~10%) only when heat waves were applied during early pod developmental stages indicates the yield loss had more to do with direct impacts of the heat waves on reproductive process than on photosynthesis. Soybean was unable to mitigate yield loss after heat waves given during late reproductive stages. This study shows that short high-temperature stress events that reduce photosynthesis and increase oxidative stress resulted in significant losses to soybean production in the Midwest, U.S. The study also suggests that to mitigate heat wave-induced yield loss, soybean needs improved reproductive and photosynthetic tolerance to high but increasingly common temperatures. Published 2015. This article is a U.S. Government work and is

  9. Early lens ablation causes dramatic long-term effects on the shape of bones in the craniofacial skeleton of Astyanax mexicanus.

    Science.gov (United States)

    Dufton, Megan; Hall, Brian K; Franz-Odendaal, Tamara A

    2012-01-01

    The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton compared to the sighted morph. We investigated the effect the lens has on the development of the surrounding skeleton, by ablating the lens at different time points during ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull more than a year later, and the developmental window during which time these effects occur. The effects of lens ablation were analyzed by whole-mount bone staining, immunohistochemisty and landmark based morphometric analyzes. Our results indicate that lens ablation has the greatest impact on the skeleton when it is ablated at one day post fertilisation (dpf) compared to at four dpf. Morphometric analyzes indicate that there is a statistically significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting plasticity in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. In contrast, the shape of the calvariae, the length of the mandible, and the number of mandibular taste buds are unaltered by lens removal. We demonstrate the plasticity of some craniofacial elements and the stability of others in the skull. Furthermore, this study highlights interactions present between sensory systems during early development and sheds light on the cavefish phenotype.

  10. Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina.

    Science.gov (United States)

    Pujic, Z; Malicki, J

    2001-06-15

    Mutation of the glass onion locus causes drastic neuronal patterning defects in the zebrafish retina and brain. The precise stratified appearance of the wild-type retina is absent in the mutants. The glass onion phenotype is first visible shortly after the formation of optic primordia and is characterized by the rounding of cells and disruption of the ventricular surface in the eye and brain neuroepithelia. With exception of the dorsal- and ventral-most regions of the brain, neuroepithelial cells lose their integrity and begin to distribute ectopically. At later stages, the laminar patterning of retinal neurons is severely disrupted. Despite the lack of lamination, individual retinal cell classes differentiate in the glass onion retina. Mosaic analysis reveals that the glass onion mutation acts cell nonautonomously within the retina and brain, as neuroepithelial cell morphology and polarity in these tissues are normal when mutant cells develop in wild-type hosts. We conclude that the glass onion mutation affects cell-cell signaling event(s) involved in the maintenance of the neuroepithelial cell layer shortly after its formation. The disruption of neuroepithelial integrity may be the cause of the neuronal patterning defects following neurogenesis. In addition, the expression of the glass onion phenotype in a subset of neuroepithelial cells as well as its onset following the initial formation of the neuroepithelial sheets indicate the presence of genetically distinct temporal and spatial subdivisions in the development of this histologically uniform tissue.

  11. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.

    Directory of Open Access Journals (Sweden)

    Michael D Blower

    2006-07-01

    Full Text Available The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC, which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.

  12. Over-expression of the PaAP1 gene from sweet cherry (Prunus avium L.) causes early flowering in Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Jing; Zhang, Xiaoming; Yan, Guohua; Zhou, Yu; Zhang, Kaichun

    2013-02-15

    A homologue of SQUAMOSA/APETALA1, designated PaAP1, was isolated from Prunus avium by reverse transcription-PCR (RT-PCR). The full length of PaAP1 cDNA is 753 bp, and it codes for a polypeptide of 250 amino acid residues. Sequence comparison revealed that PaAP1 belongs to the MADS-box gene family. Phylogenetic analysis indicated that PaAP1 shared the highest identity with SQUA/AP1 homologues from Prunus serrulata. Real-time fluorescence quantitative PCR analysis showed that PaAP1 was expressed at high levels in petal, sepal, style, and flower buds, which was slightly different from the expression pattern of AP1 of Arabidopsis thaliana. To characterize the functions of PaAP1, we assessed Arabidopsis transformed with 35S::PaAP1. A total of 8 transgenic T(1) lines with an early flowering phenotype were obtained, and a 3:1 segregation ratio of flowering time was observed in the T(2) generation of 4 lines. This study provides the first functional analysis of an SQUA/AP1 homolog from P. avium and suggests that PaAP1 is potentially useful for shortening the juvenile period in sweet cherry.

  13. Nodulation control of crack fertilization technique reduced the growth inhibition of soybean caused by short-term waterlogging at early vegetative stage

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    Koji Yamane

    2016-07-01

    Full Text Available Waterlogging is the constraint for soybean growth and yield, because soybean is often cultivated in upland fields converted from paddy in Japan. However, efficient cultivation techniques for alleviating the adverse effects have not been developed. We have proposed the new soybean cultivation technique named crack fertilization which enables yield increase due to enhancing new root growth and N acquisition by increasing nodulation. Waterlogging induces N deficiency due to the suppression of nutrient uptake by the inhibition of root growth and nodule activity. Thus, it is hypothesized that crack fertilization would be effective to alleviate the inhibition of soybean growth and yield. The soybean cultivar of Sachiyutaka was planted in 1/5000 a Wagner pots and root boxes. Two separate waterlogging treatments were imposed to soybean plants at different growth stages, V1 and R4, and crack fertilization was done at V3. After these treatments, soybean plants were sampled at R5 in 2012 and 2013 experiments, respectively. Waterlogging at V1 and R4 inhibited the growth and yield of soybean and nodule growth, and the decreases in physiological parameters of soybean such as photosynthesis, chlorophyll content, and xylem sap exudation rate were observed. The adverse effects of waterlogging at V1 were alleviated by crack fertilization at V3, whereas crack fertilization could not alleviate the adverse effects of waterlogging at R4. Thus, crack fertilization after waterlogging at early vegetative stage would be the cultivation technique that enables to alleviate the adverse effects.

  14. Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells.

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    Yi Cao

    Full Text Available Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL, caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL, caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6(nclf/nclf cerebellar cells and compared them to wild-type and CbCln3(Δex7/8/Δex7/8 cerebellar cells. CbCln6(nclf/nclf cells and CbCln3(Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6(nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6(nclf/nclf and CbCln3(Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3(Δex7/8 and Cln6(nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.

  15. 2349例心脏瓣膜置换术早期死亡原因分析%Early death causes in 2349 patients who receiving heart valve replacement

    Institute of Scientific and Technical Information of China (English)

    陈海生; 刘盛华; 钟志敏; 谢翠贤; 林秋伟

    2010-01-01

    目的 分析2349例心脏瓣膜置换术病人的死亡原因,以期进一步提高治疗水平.方法 1995年1月至2007年12月,2349例心脏瓣膜病病人接受人工心脏瓣膜置换手术.其中二尖瓣置换术(MVR)1333例,主动脉瓣置换术(AVR)271例,二尖瓣、主动脉瓣同期置换术(DVR)736例,三尖瓣置换术(TVR)9例.结果 早期病死率1995年至1999年6.81%,2000年至2004年3.22%,2005年至2007年2.82%.全组总早期病死率3.40%.结论 心脏瓣膜置换术早期死亡的原因主要是低心排血量综合征、肾功能衰竭、心律失常、肺部感染、脑血管意外、左室破裂和多器官系统功能衰竭等.%Objective The early causes of death were analyze in 2349 patients who had undergone heart valve replacement.Methods Methods From January 1995 to December 2007,2349 patients with heart valve diseases received heart valve replacement.1109 cases were male and 1240 were female.The mean age of the patients was(41±19)years old.1962 cases had rheumatic heart valve disease,308 had congenital heart valve disease,39 had infective endocarditis,29 underwent reintervention by heart valve replacement,11 had Marfan syndrome.34 cases with coronary heart disease underwent heart valve prosthesis implantation and coronary artery bypass grafting.Mitral valve replacement(MVR)was performed in 1333 patients,aortic valve replacement(AVR)in 271,double valves replacement(DVR)in 736 and tricuspid valve replacement(TVR)in 9.There were 3075 mechanical valves and 10 bioprosthetic valves.Results From 1995 to 1999,death occurred in 16 of the 235 cases,early mortality rate was 6.81%.From 2000 to 2004,death occurred in 35 of the 1087 cases,early mortality rate was 3.22%.From 2005 to 2007,there were 29 deaths among 1027 cases,with an early mortality rate of 2.82%.Overall early mortality rate was 3.40%.The early mortality rate was 2.32%(31 in 1333 cases)in patients who underwent MVR,3.32% (9 in 271)in patients who underwent AVR,5.24%(40 in 736)in

  16. Very Early Prescient Experimental and Theoretical Nano/Microcluster-Scale-Physics Root-Cause Ultimate-Origins: History: EMET!!!/TRUTH!!!

    Science.gov (United States)

    Gregson, Victor; Kubo, Ryogiro; Siegel, Edward Carl-Ludwig

    2013-03-01

    Siegel[Phys.Stat.Sol.(a)11,45(72)] possibly first experimental nanoscale-physics/metallurgy/ceramics(VS CNRS Mdm.-Pres.resume-claims),following always-seminal Kubo[Phys. Lett.1,49(62);J.Phys.Soc.Jpn.:17,965(62); 21,1765(66); Comm.SS Phys.1,168 (68); J.Phys.Colloques,38,C2-69(77).]-Fulde[(1960s)]-Matsubara et. al.[(1960s]-Matsubara-Siegel[Intl.Conf.Lattice-Dym.(77);Statphys-13(77);ICMAO(77);Scripta Met.13,913(79)] as reviewed by Sugano[Microcluster-Physics(81)], very early experimental hardness/bulk-modului/shear-moduli versus/ connection to Dempsey[Phil.Mag. 8,86,285(63)] electrical-resistivity trends with cation-atomic-number of hot/cold-pressed ceramics versus Mott topological-disorder: Siegel: powders[Mtls.Sci.Eng.8,6 323(71);Phys.Stat.Sol.(a)11, 45(72) ;Semis, &Insuls.5:39,47,62 (79)] /glasses[J.Nonxline-Sols.40,453(80); NYAS Conf.Atomic & Molecular Glasses, Ann.NYAS(80); Ferroelectrics 34,1,127(81)]/ liquids[Phys.& Chem.Liqs.:4(4)(75);5(1)(76)] / slushes (!!!)/ blends /ferrofluids[Intl Conf. Ferrofluids, M. Zahn ed.(84)]/nanophysics of Goudschmidt [Interstitial-Alloys,(69)] transition-metalloids: carbides, nitrides, borides, hydrides, carbon [Phys.Stat.Sol.(a)11,45(72); Semis.&Insuls.5: 39,47,62(79)]) and proton-irradiated diamond Little[(1960s]-predicted hyper/superconducting polydiacetylene(???) quantum-wires [3rd World Cong.SC, Munich(92), Appl.-SC,1,10,1949(93); TWO OTHER PAPERS SPIKED BY ANL/DOE EDITORS!!! AS USUAL!!!: GOOGLE:

  17. Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation.

    Science.gov (United States)

    Burnworth, B; Popp, S; Stark, H-J; Steinkraus, V; Bröcker, E B; Hartschuh, W; Birek, C; Boukamp, P

    2006-07-27

    Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

  18. 基于WebGIS的畜禽养殖废弃物对农田环境污染预警系统研究%WebGIS-based Early Warning System of Farmland Environmental Pollution Caused by Livestock Waste

    Institute of Scientific and Technical Information of China (English)

    阎波杰; 潘瑜春; 吴文英; 汤文静; 甘秋玲; 阮云娟

    2011-01-01

    [目的]为了快速、实时动态地获取区域内畜禽养殖废弃物对农田环境污染情况。[方法]以WebGIS为空间信息平台,构建了网络化、数字化的畜禽养殖废弃物对农田环境污染预警系统。[结果]系统主要实现了畜禽养殖废弃量计算、畜禽养殖相关信息查询与分析、农田畜禽养殖废弃物氮负荷量估算、畜禽养殖废弃物对农田环境污染预警及结果可视化输出等。[结论]该研究可为畜禽废弃物对环境污染的相关研究提供科学依据。%[Objective]The paper was to quickly get the real-time dynamic status of regional farmland environmental pollution caused by livestock wastes.[Method] With WebGIS as spatial information platform,the network and digital early warning system of farmland environmental pollution caused by livestock wastes was established.[Result] The system realized the functions such as livestock wastes calculation,livestock information query and analysis,nitrogen load quantity estimation of livestock waste,early warning of farmland environmental pollution caused by livestock wastes and visual display of result.[Conclusion] The paper provided scientific basis for the relevant research on farmland environmental pollution caused by livestock wastes.

  19. Early administration of therapeutic anticoagulation following intravenous thrombolysis for acute cardiogenic embolic stroke caused by left ventricular thrombus: case report and topic review

    Directory of Open Access Journals (Sweden)

    Rick eGill

    2015-02-01

    Full Text Available Cardiogenic cerebral embolism represents 20% of all acute ischemic strokes with one third of these being caused by left ventricular thrombus (LVT. LVT is not a contraindication for treatment with intravenous recombinant tissue plasminogen activator (IV rtPA for acute ischemic stroke (AIS. However the subsequent treatment of a potentially unstable LVT is contraindicated for 24 hours following the use of IV rtPA according to current guidelines. We present a 66-year-old man with AIS treated with IV rtPA. Echocardiogram shortly after treatment demonstrated both a large apical and septal thrombus in the left ventricle and at 12 hours post IV rtPA infusion, therapeutic anticoagulation with heparin was started without complication. In practice, the action of IV rtPA outlasts its apparent half-life because of thrombin-binding and the prolonged effects and longer half-life of its product, plasmin, however the pharmacokinetics do not warrant prolonged avoidance of therapeutic anticoagulation when clinically indicated. Our case demonstrates that anticoagulation for potentially unstable LVT can be safely initiated at 12 hours following IV rtPA treatment for AIS.

  20. Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

    Science.gov (United States)

    Aaby, Peter; Andersen, Andreas; Martins, Cesário L; Fisker, Ane B; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

    2016-01-01

    Background BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). Methods During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. Setting MV RCT conducted in urban Guinea-Bissau 2003–2009. Interventions Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Main outcome measure Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. Results First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Conclusions Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed. PMID:28011813

  1. Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy.

    Science.gov (United States)

    Izquierdo, Irene; Rosa, Isaac; Bravo, Susana Belén; Guitián, Esteban; Pérez-Serra, Alexandra; Campuzano, Oscar; Brugada, Ramon; Mangas, Alipio; García, Ángel; Toro, Rocio

    2016-10-04

    Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers. We developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Predictors of medical student remediation and their underlying causes: early lessons from a curriculum change in the University of Auckland Medical Programme.

    Science.gov (United States)

    Grainger, Brian; Yielder, Jill; Reid, Papaarangi; Bagg, Warwick

    2017-08-11

    The purpose of this study was to identify predictors of remediation in a medical programme and assess the underlying causes and the quality of remediation provided within the context of a recent curriculum change. A mixed methods study incorporating a retrospective cohort analysis of demographic predictors of remediation during 2013 and 2014, combined with thematic qualitative analysis of educator perspectives derived by interview on factors underlying remediation and the quality of that currently provided by the faculty. 17.7% of all students required some form of remedial assistance and 93% of all students offered remediation passed their year of study. Multivariate analysis showed international students (OR 4.59 95% CI 2.62-7.98) and students admitted via the Māori and Pacific Admission Scheme (OR 3.43 2.29-5.15) were significantly more likely to require remediation. Male students were also slightly more likely than their female classmates to require assistance. No effect was observed for rural origin students, completion of a prior degree or completion of clinical placement in a peripheral hospital. Knowledge application and information synthesis were the most frequently identified underlying problems. Most faculty believed remediation was successful, however, flexibility in the programme structure, improved diagnostics and improved access to dedicated teaching staff were cited as areas for improvement. Remediation is required by nearly a fifth of University of Auckland medical students, with MAPAS and international students being particularly vulnerable groups. Remediation is largely successful, however, interventions addressing reasoning and knowledge application may improve its effectiveness.

  3. Cancer treatment -- early menopause

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000912.htm Cancer treatment - early menopause To use the sharing features on this page, please enable JavaScript. Certain types of cancer treatments can cause women to have early menopause. This ...

  4. 儿童医院住院早期新生儿134例死亡原因分析%Analysis on causes of 134 early neonatal death in children s hospital

    Institute of Scientific and Technical Information of China (English)

    李敏; 沈云琳; 刘万红; 刘霞; 龚小慧

    2011-01-01

    目的:回顾性总结并分析上海市儿童医院住院早期新生儿死亡病例的主要死因.方法:调查上海市儿童医院1997年1月~2009年12月死亡住院新生儿的病历资料,分析住院早期新生儿死亡病例的临床情况及其主要死因.结果:1997年1月~2009年12月共收治住院新生儿18061例,其中死亡201例.医治无效死亡的生后1周内早期新生儿134例,其中早产A 59例,足月儿75例,占新生儿死亡66.67%,多数在出生后3天内死亡,在生后<24 h,24~72 h,4~7天,早产儿和足月儿死亡分别为27例(45.76%)、18例(30.51%)、14例(23.73%);35例(46.67%)、16例(21.33%)、24例(32.00%).早期新生儿主要死因前三位:早产儿为呼吸窘迫综合征、极低或超低出生体重儿并发肺炎和重度围产期窒息,足月儿为先天畸形、重度围产期窒息和败血症.结论:为降低住院新生儿的病死率,新生儿科医生应尽早识别出危重新生儿,按各种疾病的高度危险期积极救治,并提高早产儿的监护和治疗水平.%Objective: To summarize and analyze the main causes of early neonatal death in Shanghai children ' s hospital. Methods; The medical records of early neonatal death in the hospital from January 1997 to December 2009 were investigated, the clinical conditions and the main causes of the early neonatal death were analyzed. Results; 18 061 neonates hospitalized in the hospital from January 1997 to December 2009, and 201 of them died. The proportion of early neonatal death within one week after birth was 66. 67% (134 cases) , including 59 premature infants and 75 mature infants, most of the neonates died within 3 days after birth; the mortalities of prema-ture infants within 24 hours, 24-72 hours and 4-7 days after birth were 45. 76% (27 cases) , 30. 51% ( 18 cases) , 23.73% ( 14 cases) , respectively; and the mortalities of mature infants within 24 hours, 24 ~ 72 hours and 4-7 days after birth were 46. 67% (35 cases) , 21. 33% (16 cases

  5. Causes of late diagnosis of the reproductive organs’ cancer in the opinion of suffering women from urban and rural areas of Lublin as an indicator of the condition of the early cancer detection system: a preliminary report

    Science.gov (United States)

    Charzyńska-Gula, Marianna; Szadowska-Szlachetka, Zdzisława; Bartoszek, Agnieszka; Stanisławek, Andrzej

    2014-01-01

    Introduction Tumours as well as the cardiovascular diseases are the leading causes of deaths in Poland. This article contains excerpts from research on complex causes of late diagnosis of cancer among the region's residents. Aim of the study One of the specific aims of the research undertaken was to learn about subjective assessment of women suffering from cancer taking into account its late diagnosis. Material and methods The research was conducted on 130 women with diagnosed cancer of reproductive organs in the late stage of the disease, who were in oncological care. The method of diagnostic survey in the form of a questionnaire was developed for the study. Results The research reveals that the place of living has an impact on the opinions of suffering women as for the causes of late diagnosis of cancer and, secondly, that their oncological awareness is low. Conclusions In the examined group, cancer awareness of women already having cancers – irrespective of the environment of settling, was low and did not constitute the grounds for taking pro-health decisions in the area of the early diagnostic testing of cancer. This fully confirms the need for the research on effective tools to increase the awareness, particularly in the population of healthy persons, including menopausal and postmenopausal women.The opinions indirectly indicate a weaker organization and effectiveness of the activities of the cancer prevention programs in the country than those organized in the city. PMID:26327851

  6. Causes of late diagnosis of the reproductive organs’ cancer in the opinion of suffering women from urban and rural areas of Lublin as an indicator of the condition of the early cancer detection system: a preliminary report

    Directory of Open Access Journals (Sweden)

    Renata Domżał-Drzewicka

    2014-06-01

    Full Text Available Introduction: Tumours as well as the cardiovascular diseases are the leading causes of deaths in Poland. This article contains excerpts from research on complex causes of late diagnosis of cancer among the region’s residents. Aim of the study: One of the specific aims of the research undertaken was to learn about subjective assessment of women suffering from cancer taking into account its late diagnosis. Material and methods: The research was conducted on 130 women with diagnosed cancer of reproductive organs in the late stage of the disease, who were in oncological care. The method of diagnostic survey in the form of a questionnaire was developed for the study. Results: The research reveals that the place of living has an impact on the opinions of suffering women as for the causes of late diagnosis of cancer and, secondly, that their oncological awareness is low. Conclusions: 1. In the examined group, cancer awareness of women already having cancers – irrespective of the environment of settling, was low and did not constitute the grounds for taking pro-health decisions in the area of the early diagnostic testing of cancer. This fully confirms the need for the research on effective tools to increase the awareness, particularly in the population of healthy persons, including menopausal and postmenopausal women. 2. The opinions indirectly indicate a weaker organization and effectiveness of the activities of the cancer prevention programs in the country than those organized in the city.

  7. A retrospective study of early dental implant failure caused by peri-implantitis%种植体周围炎导致牙种植早期失败的原因分析

    Institute of Scientific and Technical Information of China (English)

    徐鹏; 李晓东; 裴仲秋; 杨小竺; 黄元丁; 白石; 黄弘; 谭迎赟; 王黎

    2012-01-01

    Objective To analyze the causes associated with the early failure of dental implant to improve successful rate. Methods There were 57 patients with implant loosening or removed before repairing who received dental implant surgery from January 2006 to May 2011 in our department were reviewed and analyzed. Results Among these 57 patients, there were 63 failed implants. Most of the early failure occurred within the first month after implantation. Among all of them, 36 were caused by mucosa-derived peri-implanti-tis, 12 by teeth-derived peri-implantitis, 6 by simple infective peri-implantitis, 6 by aseptic peri-implantitis, and 3 by other factors. Conclusion Causes of early dental implant failure are complex. Postoperative wound infection is the most important one.%目的 分析口腔种植早期失败的原因,以提高种植早期成功率.方法 以种植体修复前松动脱落或被取出为种植失败的标准,收集并分析2006年1月至2011年5月在我科口腔医院种植科接受口腔种植的57例早期失败的病例资料,对导致失败的原因进行初步分析.结果 57例患者中,失败种植体共63枚.种植手术后第1个月是最危险时间段.失败原因分析:黏膜源性种植体周围炎所致36枚、牙源性种植体周围炎所致12枚、单纯感染性种植体周围炎所致6枚、无菌性种植体周围炎所致6枚、其他原因3枚.结论 致口腔种植早期失败的原因复杂,其中术后伤口黏膜感染为最主要因索.

  8. Clinical observation of early traction for the treatment of diplopia caused by orbital blowout fracture%早期牵引治疗眼眶爆裂性骨折所致复视临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘瑞芳; 万新顺; 韩丽英

    2009-01-01

    Objective To observe clinical efficacy and indications of the treatment of the early trac-tion for the treatment of diplopia caused by orbital blowout fracture.Methods 38cases of 52orbital blowout fracture underwent the traction treatment, of whom unimproved with drug therapy, were analyzed retrospective-ly.Follow-up were 6 months.Results in 38 patients treated by traction,diplopia symptoms of 27 cases disap-peared, four cases improved, seven cases invalid.no complications were found.Conclusions Early traction for the treatment of diplopia caused by orbital blowout fracture is a simple,effective method between the drug and surgical treatment With use value.%目的 观察早期牵引治疗眼眶爆裂性骨折所致复视临床疗效,探讨牵引治疗适应证.方法 回顾性观察眼眶爆裂性骨折病52例52只眼.其中38例经药物治疗无效后应用手法行牵引治疗.随访期为6个月.结果 38例患者经牵引治疗后27例复视症状消失,4例好转,7例无效.未见治疗引起的并发症.结论 早期牵引治疗眼眶爆裂性骨折所致复视方法简单,有效,是一种较为实用治疗方法.

  9. Early age of alcohol initiation is not the cause of alcohol use disorders in adulthood, but is a major indicator of genetic risk. A population-based twin study.

    Science.gov (United States)

    Ystrom, Eivind; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

    2014-11-01

    An early age of alcohol initiation (AAI) is associated with and has been hypothesized to be a cause of alcohol use disorders (AUD) in adulthood. Results from twin studies, however, indicate that AAI is an indicator of risk for AUD. We aimed to test a causal hypothesis versus a risk indicator hypothesis for the relationship between early AAI and AUD. A population-based twin study using biometric twin modelling. Norway. A population-based sample of 1336 Norwegian twins. Life-time DSM-IV AUDs were assessed by structured clinical interview and AAI by questionnaire. The risk indicator model in which the association between AAI and AUD was explained by common vulnerability was the best fitted to the data. The heritability was 37% [95% confidence interval (CI) = 21%, 53%] for AAI and 62% (95% CI = 51%, 73%) for AUD. Genetic risk for AAI accounted for 44% (95% CI = 17%, 71%) of the total genetic risk for AUD and the correlation between genetic factors for AAI and AUD was -0.66 (95%CI -0.87, -0.46). Individual-specific environmental risk for AAI explained only 1% (95% CI = 0%, 3%) of the risk for AUD. Shared environmental factors did not influence AUD, but accounted for 25% (95% CI = 7%, 35%) of the variance in AAI. The association between early age of alcohol initiation and alcohol use disorders in later life does not reflect a causal relationship, but is due almost entirely to common genetic risk factors. © 2014 Society for the Study of Addiction.

  10. Prefrontal mRNA expression of long and short isoforms of D2 dopamine receptor: Possible role in delayed learning deficit caused by early life interleukin-1β treatment.

    Science.gov (United States)

    Schwarz, Alexander P; Trofimov, Alexander N; Zubareva, Olga E; Lioudyno, Victoria I; Kosheverova, Vera V; Ischenko, Alexander M; Klimenko, Victor M

    2017-08-30

    Long (D2L) and short (D2S) isoform of the D2 dopamine receptor are believed to play different roles in behavioral regulation. However, little is known about differential regulation of these isoforms mRNA expression during the process of learning in physiological and pathological states. In this study, we have investigated the combined effect of training in active avoidance (AA) paradigm and chronic early life treatment with pro-inflammatory cytokine interleukin (IL)-1β (1μg/kg i.p., P15-21) on D2S and D2L dopamine receptor mRNA expression in the medial prefrontal cortex (mPFC) of adult rats. We have shown differential regulation of D2 short and long mRNA isoform expression in the mPFC. There was no effect of AA-training on D2S mRNA expression, while D2L mRNA was downregulated in AA-trained control (intact and saline-treated) animals, and this effect was not observed in rats treated with IL-1β. D2S mRNA expression level negatively correlated with learning ability within control (saline-treated and intact) groups but not in IL-1β-treated animals. Thus, prefrontal expression of distinct D2 dopamine receptor splice variants is supposed to be implicated in cognitive decline caused by early life immune challenge. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Influence of Mechanical Transplantation on the Growth Period of Early Rice and Its Causes%机插对早稻生育期的影响及原因探究

    Institute of Scientific and Technical Information of China (English)

    张坤; 吕伟生; 胡水秀; 曾勇军; 潘晓华; 石庆华

    2016-01-01

    To study the effect of mechanical transplanting on growth period of early rice and its causes,a one⁃year field experiment was conducted with early rice combination Zhuliangyou30 by means of three planting methods,namely, artificial transplanting, mechanical transplanting and tray nursing seedlings transplanted by hand.The results showed that the seedling quality of the artificial transplanting was significantly better than that of the tray nursing seedlings,machine did more damage to the seedlings than hand,tray nursing seedlings trans⁃planted by hand (TNSTH) and tray nursing seedlings transplanted by machine (MT) delayed 1 and 3 days of the growth period compared with artificial transplanting,the delay of the growth period of TNSTH was caused by the extension of the critical period from transplanting to effective tiller,that of MT was caused by the extension of the period from transplanting to the heading stage,the seedling quality was poor,the dry matter accumulation of the aerial part was little and planting injury was the main cause for the delay of the growth period of early rice transplanted by machine.In practical production the delay of the growth period caused by mechanical transplan⁃ting can be alleviated through cultivating strong seedlings, improving the quality of machanical transplanting and so on.%以株两优30为材料,采用传统手栽、机插秧苗手栽(机手)和机插秧苗机插(机插)3种种植方式,研究机插对早稻生育期影响及其原因。结果表明:传统手栽秧苗素质极显著优于秧盘育秧;机插对秧苗的损伤程度大于手栽;机手和机插生育期分别较传统手栽延迟1 d和3 d,机手生育期延迟由移栽至有效分蘖临界期( N-n,N表示主茎叶片数,n表示水稻节间数,下同)延长引起,机插是移栽至抽穗期延长引起的;秧苗素质差,地上部分干物质积累量少,植伤重是早稻机插生育期推迟主要

  12. Analysis of clinical features for myelofibrosis with infection%原发性骨髓纤维化患者感染的临床特点分析

    Institute of Scientific and Technical Information of China (English)

    陈晓文; 鲁海燕; 夏海龙

    2011-01-01

    Objective To study the clinical features for myelofibrosis with infection. Methods We studied retrospectively the clinical data of MF patients with infection. Results The incidence rate of MF complicated with infection in MF was 45.8%. The most common infectious location was lungs ( 45.5% ). The majority of disease producing germ was gram - negative bacteria ( G - ), with the infection rate of 57.1%. The incidence rate of infection was 46.2% in the male group and 45.4% in the female group ( P > 0. 05 ). The infection rate was 69.2% in the aged group ( > 60 year s)and 18.2% in non -aged group ( < 60 years ) (P <0.05). The incidence rate of two groups of leucocyte count < 4.0 × 109L-1 and > 4.0 × 109 L-1were respectively 66.7% and 29.6% (P < 0. 05). The incidence rate were respectively 69.2% in the group of blood platelet count <20 × 109 L-1 and 37.1% of blood platelet count > 20 × 109 L-1 (P <0.05). The incidence rate were respectively 58.6% in the group of hemoglobin content < 90 g/L and 26.3% of hemoglobin content > 90 g/L ( P < 0.05 ). The incidence rate of two groups of albumin count < 35 g/L and > 35 g/L were respectively 64.3% and 38.2% ( P < 0.05). Conclusion MF complicated with infection has high incidence possible risk factors including eld, decrease of leucocyte, blood platelet and hemoglobin. Positive control of possible risk factors is the important intervention of infection prevention.%目的 研究原发性骨髓纤维化(IMF)患者感染的临床特点.方法 回顾分析对IMF并发感染病例的临床资料,并进行统计分析.结果 48例IMF患者中感染率为45.8%.最常见的感染部位是肺部,占45.5%.感染的绝大多数病原菌为革兰氏阴性(Gˉ)菌,占57.1%.男性患者和女性患者感染率分别为46.2%和45.4%(P>0.05).老年组(>60岁)患者和非老年组(<60岁)患者感染率分别为69.2%和18.2%(P<0.05).白细胞数<4.0×109L-1

  13. Ontong Java volcanism initiated long-term climate warming that caused substantial changes in terrestrial vegetation several tens of thousand years before the onset of OAE1a (Early Aptian, Cretaceous)

    Science.gov (United States)

    Keller, Christina E.; Hochuli, Peter A.; Giorgioni, Martino; Garcia, Therese I.; Bernasconi, Stefano M.; Weissert, Helmut

    2010-05-01

    . percentages indicate a rise in temperatures. Maximum temperatures (suggested by a dominance of Classopollis spp.) were only reached after the most negative inorganic C-isotope values and after the onset of OAE1a. Our study shows that the volcanically-induced increase in pCO2, which ultimately led to OAE1a caused a substantial climate warming that seriously affected terrestrial vegetation. References: Arthur, M.A., 2000, Volcanic contributions to the carbon and sulfur geochemical cycles and global change, in Sigurdsson, H., Houghton, B., McNutt, S.R., Rymer, H., and Stix, J., eds., Encyclopedia of Volcanoes, Academic Press, p. 1045-1056. Channell, J.E.T., Cecca, F., and Erba, E., 1995, Correlations of Hauterivian and Barremian (Early Cretaceous) stage boundaries to polarity chrons: Earth and Planetary Science Letters, v. 134, p. 125-140. Hochuli, P.A., Menegatti, A.P., Weissert, H., Riva, A., Erba, E., and Silva, I.P., 1999, Episodes of high productivity and cooling in the early Aptian Alpine Tethys: Geology, v. 27, p. 657-660. Jahren, A.H., Arens, N.C., Sarmiento, G., Guerrero, J., and Amundson, R., 2001, Terrestrial record of methane hydrate dissociation in the Early Cretaceous: Geology, v. 29, p. 159-162. Méhay, S., Keller, C.E., Bernasconi, S.M., Weissert, H., Erba, E., Bottini, C., and Hochuli, P.A., 2009, A volcanic CO2 pulse triggered the Cretaceous Oceanic Anoxic Event 1a and a biocalcification crisis: Geology, v. 37, p. 819-822. Tejada, M.L.G., Suzuki, K., Junichiro, K., Rodolfo, C., J., M.J., Naohiko, O., Tatsuhiko, S., and Yoshiyuki, T., 2009, Ontong Java Plateau eruption as a trigger for the early Aptian oceanic anoxic event: Geology, v. 37, p. 855-858.

  14. 超声对药物流产后持续阴道出血的诊断及原因分析%Ultrasound diagnosis and analysis of cause of prolonged vaginal bleeding after medical termination of early pregnancy

    Institute of Scientific and Technical Information of China (English)

    徐凤娟

    2011-01-01

    目的 探讨超声对药物流产后持续阴道出血患者的声像图特征及其相应的原因浅析.方法 对65例药物流产后7~20 d仍有持续阴道出血患者进行经腹及经阴道超声检查,观察子宫形态、大小,宫腔组织回声及血流情况.结果 药物流产后持续阴道出血患者的声像图特征:①子宫内膜粗糙、宫内小片状、团块样强回声,彩色多普勒超声提示无明显血流信号、局部星点状或丰富血流信号,其原因多为绒毛或滋养细胞残留;②宫内出现小孕囊或孕囊继续增大提示药物流产失败;③附件区包块(本文为异位妊娠误用药物流产);④子宫肌瘤且子宫位置极度后倾后屈合并早孕(药物流产后胚胎物排出不够通畅,导致阴道出血时间延长).结论 通过超声对药物流产后持续阴道出血患者的声像图特征及其相应原因的分析,认为经腹及经阴道超声检查对临床处理具有重要指导意义.%Objective To investigate ultrasound characteristics and analyze their corresponding causes for prolonged vaginal bleeding after medical termination of early pregnancy. Methods Sixty - five cases who still had prolonged vaginal bleeding 7 - 20 days after drug - induced abortion were examined with transabdominal sonography ( TAS ) and transvaginal sonography ( TVS ) to observe the uterine shape, size, the situation of intrauterine remainder and blood flow. Results The characteristic ultrasonographic features and causes for prolonged vaginal bleeding after med ical termination of pregnancy were shown as four different types: ①The endometrial roughness, intrauterine thin pieces echo and intrauterine blob - like echo were observed; and the color Doppler flow signals indicated no ohvious flows, local satellite signal points, or rich blood flows. It was often caused by residual villous trophoblast cells. ②Intrauterine gestational sac or a small gestational sac suggested drug - induced abortion failure

  15. A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.

    Science.gov (United States)

    Passamonti, Francesco; Thiele, Jürgen; Girodon, Francois; Rumi, Elisa; Carobbio, Alessandra; Gisslinger, Heinz; Kvasnicka, Hans Michael; Ruggeri, Marco; Randi, Maria Luigia; Gangat, Naseema; Vannucchi, Alessandro Maria; Gianatti, Andrea; Gisslinger, Bettina; Müllauer, Leonhard; Rodeghiero, Francesco; d'Amore, Emanuele S G; Bertozzi, Irene; Hanson, Curtis A; Boveri, Emanuela; Marino, Filippo; Maffioli, Margherita; Caramazza, Domenica; Antonioli, Elisabetta; Carrai, Valentina; Buxhofer-Ausch, Veronika; Pascutto, Cristiana; Cazzola, Mario; Barbui, Tiziano; Tefferi, Ayalew

    2012-08-01

    Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 10(9)/L, and prior thrombosis significantly affected survival, by multivariable Cox regression. On the basis of the hazard ratio, we assigned 2 points to age and 1 each to leukocyte count and thrombosis. So, the IPSET model allocated 867 patients into 3 risk categories with significantly different survival: low (sum of points = 0; median survival not reached), intermediate (sum = 1-2; median survival 24.5 years), and high (sum = 3-4, median survival 13.8 years). The IPSET model was further validated in 2 independent cohorts including 132 WHO-defined ET and 234 Polycythemia Vera Study Group-defined ET patients. The IPSET model was able to predict the occurrence of thrombosis, and not to predict post-ET myelofibrosis. In conclusion, IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 10(9)/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.

  16. Monitoring of all-cause mortality in Belgium (Be-MOMO): a new and automated system for the early detection and quantification of the mortality impact of public health events.

    Science.gov (United States)

    Cox, Bianca; Wuillaume, Françoise; Van Oyen, Herman; Maes, Sophie

    2010-08-01

    Be-MOMO is the monitoring of all-cause death registry data in Belgium. The new methods are described and the detection and quantification of outbreaks is presented for the period April 2006-March 2007. Sensitivity, specificity and timeliness are illustrated by means of a temporal comparison with known health events. Relevant events are identified from important mortality risks: climate, air pollution and influenza. Baselines and thresholds for deaths by gender, age group, day and week are estimated by the method of Farrington et al. (J R Stat Soc Ser A, 159:547-563, 1996). By adding seasonal terms to the basic model, a complete 5-year reference period can be used, while a reduction of noise allows the application to daily counts. Ignoring two false positives, all flags could be classified into five distinct outbreaks, coinciding with four heat periods and an influenza epidemic. Negative deviations from expected mortality in autumn and winter might reflect a displacement of mortality by the heat waves. Still, significant positive excess was found during five influenza weeks. Correcting for the delay in registration of deaths, outbreaks could be detected as soon as 1-2 weeks after the event. The sensitivity of Be-MOMO to different health threats suggests its potential usefulness in early warning: mortality thresholds and baselines might serve as rapid tools for detecting and quantifying outbreaks, crucial for public health decision-making and evaluation of measures.

  17. PKRP 术后早期出血致膀胱填塞原因分析与防治策略%Causes Analysis of 35 Patients with Bladder Tamponade Induced by Early Bleeding after Transurethral Plasmakinetic Resection of Prostate

    Institute of Scientific and Technical Information of China (English)

    何运胜; 刘晓波

    2014-01-01

    目的:探讨经尿道等离子体双极前列腺电切术(transurethral plasmakinetic resection of prostate,PKRP)后早期出血致膀胱填塞的原因。方法回顾分析我院2005年1月—2012年1月35例 PKRP 术后24 h 内出血致膀胱填塞患者的临床资料。结果本组常规行 PKRP,术中均顺利,膀胱填塞发生于术后6 h 内28例,6~12 h 内7例。19例表现为下腹部剧痛,冲洗液鲜红或伴随冲洗液反流;16例无主诉,仅表现为冲洗液反流或停止或波动样流动。35例经 B 超检查明确膀胱填塞,重返手术室酌情采取镜下冲洗血凝块、电凝止血,或电切血凝块,或电切残留小腺体并电凝止血等处理,5 d 后出院。随访2~7年,排尿正常,无再次出血。结论膀胱痉挛是 PKRP 术后24 h 内出血致膀胱填塞的高危因素,尤其对下腹部无明显疼痛的膀胱痉挛患者,要善于观察,并及早行 B 超检查,避免延误诊断与处理。%Objective To explore the causes of bladder tamponade induced by early bleeding after transurethral plas-makinetic resection of prostate (PKRP). Methods Clinical data of 35 patients with bladder tamponade induced by early bleeding within 24 h after PKRP during January 2005 and January 2012 was retrospectively analyzed. Results All the pa-tients underwent routine PKRP of successful operation process, 28 patients had bladder tamponade within 6 h after the opera-tion, and 7 patients had bladder tamponade within 6 - 12 h after the operation, 19 patients suffered severe pain in lower abdo-men, bright red washing fluid or contraflow with washing fluid; 16 patients did not complain with contraflow, stopping or wave-like movement of washing fluid. All the 35 patients were confirmed with having the bladder tamponade by B ultrasound exami-nation, and underwent washing the blood clot under the microscope, electric coagulation hemostasis, transurethral clot or tran-surethral residual small glands electric coagulation treatment

  18. Óbitos neonatais precoces: análise de causas múltiplas de morte pelo método Grade of Membership Early neonatal mortality: an analysis of multiple causes of death by the Grade of Membership method

    Directory of Open Access Journals (Sweden)

    Eliane de Freitas Drumond

    2007-01-01

    Full Text Available Estudo de base populacional para determinar perfis de óbitos neonatais precoces ocorridos em Belo Horizonte, Minas Gerais, Brasil, de 2000 a 2003. A defini��ão dos perfis de causas amplia possibilidade de análise sob enfoque de evitabilidade, justificada pela persistência de altas taxas de mortalidade neonatal precoce. Três perfis foram gerados, a partir do enfoque de causas múltiplas, sob a perspectiva dos conjuntos nebulosos ("fuzzy sets", utilizando-se técnica Grade of Membership. Relacionaram-se esses perfis ao peso de nascimento e a natureza jurídica do hospital de ocorrência do óbito. Nos hospitais da rede privada ocorreram "óbitos dificilmente preveníveis, com menção de malformação congênita" (perfil 2. Aos hospitais do Sistema Único de Saúde (SUS associaram-se dois perfis distintos. Nos hospitais contratados/conveniados ocorreram os "óbitos passíveis de prevenção" (perfil 1 e na rede própria os "óbitos de prematuros" (perfil 3. A tipologia observada aponta para necessidade de adoção de políticas diferenciadas na rede SUS: prioritariamente, na rede contratada/conveniada, ações voltadas para credenciamento e avaliação da qualidade da assistência; e, em toda rede, adoção rotineira de protocolos assistenciais e medidas profiláticas, redutores da morbimortalidade neonatal.This population-based study aimed to determine the profile of early neonatal deaths in Belo Horizonte, Minas Gerais, Brazil, from 2000 to 2003. Profiles were analyzed from the perspective of avoidability, justified by persistently high early neonatal mortality rates in the city. Three profiles were generated for multiple causes of death from the perspective of fuzzy sets, using the Grade of Membership method. Birth weight and the hospital's corporate status were also related to the three profiles. Private hospitals were characterized by so-called "difficult-to-prevent deaths, with mention of congenital malformations" (profile 2. The

  19. Causes of automotive turbocharger faults

    Directory of Open Access Journals (Sweden)

    Jan FILIPCZYK

    2013-01-01

    Full Text Available This paper presents the results of examinations of turbocharger damages. The analysis of the causes of faults in 100 engines with turbochargers of cars, buses and trucks has been carried out. The incidence and structure of turbocharged engine faults has been compared to the causes of faults of naturally aspirated engines. The cause of damage, the possibility of early detection, the time between overhaul and the impact on engine operation for each case of fault was carried out as well. The results of examinations allowed to determine the most common causes of damages and how to prevent them.

  20. Early Diagnosis of Nosocomial Infection Caused by Pulmonary Tuberculosis in Patients with Diabetes Mellitus%唐尿病患者医院感染肺结核的早期诊断指标分析

    Institute of Scientific and Technical Information of China (English)

    张常然; 牛媛媛; 黄知敏; 林建聪; 谭清华; 邢艳利; 李延兵; 刘霞; 李鸣

    2009-01-01

    目的 减少肺结核的医院感染,研究有助于糖尿病合并活动型肺结核的早期诊断指标.方法 回顾分析某三甲医院内分泌科10年糖尿病合并活动型和非活动型肺结核316例患者的临床资料.结果 活动型和非活动型肺结核组的平均年龄分别为(55.01±12.77)岁和(61.92±11.18)岁;非活动型肺结核多有肺结核病史(22.6%),明显多于活动型肺结核组患者(13.4%)(P<0.05);活动型和非活动型肺结核患者咳嗽、咳痰症状、痰涂片找分枝杆菌的阳性率分别为48.4%、80.0%,25.2%、10.0%;活动型和非活动型肺结核组的糖化血红蛋白(GHBA1c)、C肽、空腹血糖分别为(10.74±2.95)%、(0.56±0.38)nmol/L、(13.11±5.63)mmol/L、(8.68±2.08)%、(0.66±0.48)nmol/L、(10.33±9.41)mmol/L,上述指标两组相比,差异均有统计学意义(P<0.05).结论 出现咳嗽、咳痰症状、痰涂片找分枝杆菌、无明显诱因的血糖控制差等指标有助于糖尿病合并活动型肺结核的早期诊断,尽早检查这些指标,及时隔离,可减少肺结核的医院感染.%OBJECTIVE To reduce the nosocomial infection caused by Mycobacterium tuberculosis in patients with diabetes mellitus, and study the some characteristics for early diagnosis of nosocomial infection. METHODS The clinical data of a total of 316 diabetes mellitus patients with pulmonary tuberculosis from Jan 1998 to Dec 2007 were made a retrospectively investigation. RESULTS The age was (55.01±12.77) and (61.92±11.18) years old in the patients with active and inactive pulmonary tuberculosis, respectively. The pulmonary tuberculosis history was more frequent in the patients with inactive pulmonary tuberculosis (22.6%) than those with active one (13.4%). There was significant difference for pulmonary tuberculosis history between two groups(P<0.05). The frequency of cough with profuse sputum and the sputum positive rate with M. tuberculosis were 48.4% and 80.0% vs 25.2% and 10.0% between two groups

  1. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?

    Science.gov (United States)

    Hasselbalch, Hans Carl

    2013-02-01

    The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous proliferative advantage. In addition to the JAK2V617 mutation several other mutations have been described. Recently chronic inflammation has been proposed as a trigger and driver of clonal evolution in MPNs. Herein, it is hypothesized that sustained inflammation may elicit the stem cell insult by inducing a state of chronic oxidative stress with elevated levels of reactive oxygen species (ROS) in the bone marrow, thereby creating a high-risk microenvironment for induction of mutations due to the persistent inflammation-induced oxidative damage to DNA in hematopoietic cells. Alterations in the epigenome induced by the chronic inflammatory drive may likely elicit a "epigenetic switch" promoting persistent inflammation. The perspectives of chronic inflammation as the driver of mutagenesis in MPNs are discussed, including early intervention with interferon-alpha2 and potent anti-inflammatory agents (e.g. JAK1-2 inhibitors, histone deacetylase inhibitors, DNA-hypomethylators and statins) to disrupt the self-perpetuating chronic inflammation state and accordingly eliminating a potential trigger of clonal evolution and disease progression with myelofibrotic and leukemic transformation.

  2. What Caused the Great Depression?

    Science.gov (United States)

    Caldwell, Jean; O'Driscoll, Timothy G.

    2007-01-01

    Economists and historians have struggled for almost 80 years to account for the American Great Depression, which began in 1929 and lasted until the early years of World War II. In this article, the authors discuss three major schools of thought on the causes of the Great Depression and the long failure of the American economy to return to full…

  3. A Novel Algorithm for the Assessment of Blood-Brain Barrier Permeability Suggests That Brain Topical Application of Endothelin-1 Does Not Cause Early Opening of the Barrier in Rats

    Directory of Open Access Journals (Sweden)

    D. Jorks

    2011-01-01

    Full Text Available There are a number of different experimental methods for ex vivo assessment of blood-brain barrier (BBB opening based on Evans blue dye extravasation. However, these methods require many different steps to prepare the brain and need special equipment for quantification. We here report a novel, simple, and fast semiquantitative algorithm to assess BBB integrity ex vivo. The method is particularly suitable for cranial window experiments, since it keeps the spatial information about where the BBB opened. We validated the algorithm using sham controls and the established model of brain topical application of the bile salt dehydrocholate for early BBB disruption. We then studied spreading depolarizations in the presence and the absence of the vasoconstrictor endothelin-1 and found no evidence of early BBB opening (three-hour time window. The algorithm can be used, for example, to assess BBB permeability ex vivo in combination with dynamic in vivo studies of BBB opening.

  4. Early Mover Advantages

    OpenAIRE

    Bijwaard, Govert; Janssen, Maarten; Maasland, Emiel

    2005-01-01

    This paper analyzes empirically whether and if so to what extent later entrants in the European mobile telephony industry have a disadvantage vis-à-vis incumbents and early mover entrants. To analyze this question a dynamic model of market share development and a series of static models are considered. There is clear evidence of early mover advantage, mainly caused by the influence of the penetration rate: it pays to enter when still few people have acquired a mobile telephone. Another import...

  5. Do We Know What Causes Breast Cancer?

    Science.gov (United States)

    ... Research? Breast Cancer About Breast Cancer How Does Breast Cancer Form? Changes or mutations in DNA can cause ... requests, please contact permissionrequest@cancer.org . More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  6. The Causes of the Avoidance of Violent Revolution during the Early Stage of Thailand’s Political Modernization%论泰国政治现代化初期未发生暴力革命之原因

    Institute of Scientific and Technical Information of China (English)

    杨帆

    2014-01-01

    The eraly stage of Thailand's political modernization which took place during the late 19th and early 20th century has two main stages: the first round was called Chakri Reform (1851 - 1932), which was composed of a series of reforms carried out by King Mongkut, King Chulalongkorn and King Vajiravudh; the second round was the Siamese Revolution of 1932 brought about by the Khana Ratsadon (Peoples' Party), which was founded by a group of young scholars and soldiers. Unlike most countries, Thailand's modernization in its early years was com-paratively smooth and peaceful. From the perspectives of culturology as well as Samuel Huntington's political devel-opment theory, this paper summarizes three interconnected main reasons why Thailand's early stage of modernization reform avoided violent revolution: first, the reform avoided political vacuum; second, moderate forces predomina-ted throughout the transformation; and third, the particular cultural and religious factors restrained potential popu-list storms.%泰国的政治现代化发生在19世纪末至20世纪初,其初期分为两个阶段:第一轮变革发生于1851-1932年之间,称为却克里改革,是由蒙固王、朱拉隆功王和瓦栖拉兀王祖孙三代国王发起的一系列改革;第二轮变革是1932年由主要是青年学者和少壮派军人组成的人民党发起的立宪革命。与多数国家不同,泰国的两轮改革均为较平稳而温和的渐进式变革,并未发生暴力革命。本文从分析泰国现代化初期的历史脉络出发,从亨廷顿政治发展理论和文化学的视角,将泰国早期现代化改革之所以能和平过渡的主要原因,总结为相互联系的三个方面:变革过程中政治权威未出现真空、温和势力在变革中始终占据主导地位、文化宗教因素遏制了民粹的爆发。

  7. On the Causes of the Development of Land Market in Early Modern England%试析近代早期英国土地市场发展的多维因素

    Institute of Scientific and Technical Information of China (English)

    孙小娇

    2014-01-01

    In early modern England, the land market was active, and the change of economic structure and land tenure were the primary factors for such a development.A series of events, such as Reformation and Enclosure movement, and the different landholders took part in the land market which promoted the development of land market.%近代早期英国土地市场较为活跃,经济结构及土地保有制的变化是土地市场发展的首要因素。宗教改革、圈地运动及社会各阶层积极参与土地交易等都促进了土地市场的发展。

  8. 云南小粒咖啡出现早衰的原因及防控对策%The Reasons Caused Early Decline of Coffea arabica and Its Control in Yunnan Province

    Institute of Scientific and Technical Information of China (English)

    张洪波; 李锦红; 白学慧; 郭铁英; 周华; 夏红云

    2015-01-01

    分析了近年云南小粒咖啡早衰减产问题,认为全球气温变化是一个重要的原因,连年持续干旱、冬季寒害、田间管理松弛以及锈病流行与天牛危害叠加的影响导致了云南咖啡出现早衰;提出了改善咖啡种植环境、加强水利设施建设、选种抗锈品种、防控天牛害虫、加强肥料管理的对策;特别阐述了解决云南咖啡早衰乃至云南咖啡可持续发展问题的一个根本举措,是要引进、选育和推广种植以抗锈为主的高产优质品种的观点。%Early decline has been resulting yield loss in Coffea arabica in recent years in Yunnan. It was thought that the change of global climate is one of the important affect factors. Furthermore, continuous drought for years, cold injury in Winter, field management and epidemics like coffee rust and stem borer are all considered. It thus presents that planting environment, water conservancy facilities, breeding system, disease control and fertilizer management should be strengthened and improved. And emphasizes a viewpoint that quality cultivars with high yield and resistant against leaf rust in introduction, breeding and culti-vation promotion should be considered into a basic strategy fighting early decline and even for sustainable development to Yunnan coffee.

  9. JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFNα.

    Science.gov (United States)

    Hasan, Salma; Lacout, Catherine; Marty, Caroline; Cuingnet, Marie; Solary, Eric; Vainchenker, William; Villeval, Jean-Luc

    2013-08-22

    The acquired gain-of-function V617F mutation in the Janus Kinase 2 (JAK2(V617F)) is the main mutation involved in BCR/ABL-negative myeloproliferative neoplasms (MPNs), but its effect on hematopoietic stem cells as a driver of disease emergence has been questioned. Therefore, we reinvestigated the role of endogenous expression of JAK2(V617F) on early steps of hematopoiesis as well as the effect of interferon-α (IFNα), which may target the JAK2(V617F) clone in humans by using knock-in mice with conditional expression of JAK2(V617F) in hematopoietic cells. These mice develop a MPN mimicking polycythemia vera with large amplification of myeloid mature and precursor cells, displaying erythroid endogenous growth and progressing to myelofibrosis. Interestingly, early hematopoietic compartments [Lin-, LSK, and SLAM (LSK/CD48-/CD150+)] increased with the age. Competitive repopulation assays demonstrated disease appearance and progressive overgrowth of myeloid, Lin-, LSK, and SLAM cells, but not lymphocytes, from a low number of engrafted JAK2(V617F) SLAM cells. Finally, IFNα treatment prevented disease development by specifically inhibiting JAK2(V617F) cells at an early stage of differentiation and eradicating disease-initiating cells. This study shows that JAK2(V617F) in mice amplifies not only late but also early hematopoietic cells, giving them a proliferative advantage through high cell cycling and low apoptosis that may sustain MPN emergence but is lost upon IFNα treatment.

  10. Detection of CTX-M-15 beta-lactamases in Enterobacteriaceae causing hospital- and community-acquired urinary tract infections as early as 2004, in Dar es Salaam, Tanzania.

    Science.gov (United States)

    Manyahi, Joel; Moyo, Sabrina J; Tellevik, Marit Gjerde; Ndugulile, Faustine; Urassa, Willy; Blomberg, Bjørn; Langeland, Nina

    2017-04-17

    The spread of Extended Spectrum β-lactamases (ESBLs) among Enterobacteriaceae and other Gram-Negative pathogens in the community and hospitals represents a major challenge to combat infections. We conducted a study to assess the prevalence and genetic makeup of ESBL-type resistance in bacterial isolates causing community- and hospital-acquired urinary tract infections. A total of 172 isolates of Enterobacteriaceae were collected in Dar es Salaam, Tanzania, from patients who met criteria of community and hospital-acquired urinary tract infections. We used E-test ESBL strips to test for ESBL-phenotype and PCR and sequencing for detection of ESBL genes. Overall 23.8% (41/172) of all isolates were ESBL-producers. ESBL-producers were more frequently isolated from hospital-acquired infections (32%, 27/84 than from community-acquired infections (16%, 14/88, p community, respectively. Bla SHV-12 genotypes were only detected in hospital-acquired infections. bla CTX-M-15 is a predominant gene conferring ESBL-production in Enterobacteriaceae causing both hospital- and community-acquired infections in Tanzania.

  11. Early Parkinson's May Prompt Vision Problems

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_167131.html Early Parkinson's May Prompt Vision Problems Changes in sight could ... in vision may be an early sign of Parkinson's disease, researchers report. The neurodegenerative condition is caused ...

  12. Can Thymus Cancer Be Found Early?

    Science.gov (United States)

    ... Thymus Cancer Early Detection, Diagnosis, and Staging Can Thymus Cancer Be Found Early? Screening is testing for ... Ask Your Doctor About Thymus Cancer? More In Thymus Cancer About Thymus Cancer Causes, Risk Factors, and ...

  13. Can Thyroid Cancer Be Found Early?

    Science.gov (United States)

    ... Thyroid Cancer Early Detection, Diagnosis, and Staging Can Thyroid Cancer Be Found Early? Many cases of thyroid cancer ... Health Care Team About Thyroid Cancer? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  14. Can Testicular Cancer Be Found Early?

    Science.gov (United States)

    ... Testicular Cancer Early Detection, Diagnosis, and Staging Can Testicular Cancer Be Found Early? Most testicular cancers can be ... Ask Your Doctor About Testicular Cancer? More In Testicular Cancer About Testicular Cancer Causes, Risk Factors, and Prevention ...

  15. Problems concerning food production, supply and use caused by radioactive deposition: A study directed towards needs for early decision making after radioactive fallout; Radiakproblem inom livsmedelssektorn: En studie inriktad paa behoven foer beslutsfattande i tidigt skede efter radioaktivt nedfall

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, R.

    1995-12-01

    The primary aim of this study is to analyze and describe how a radioactive deposition after nuclear weapons employment outside Sweden would affect the domestic food production in a short time perspective and in the sequence of events from primary production over processing and transport to food consumption. The study is an attempt at a comprehensive treatment of knowledge needed as a basis for decisions on operative issues, often of a time-urgent nature. Actions to alleviate the problems pertinent to the food supply in the event of radioactive fallout are also discussed, although without any claim of exhaustive coverage. Other aspects, as the economical consequences of the disturbances due to the fallout situation (or of possible counteractions) are not dealt with, however. With certain restrictions mentioned in the text the results are also applicable in connection with radioactive deposition caused by accidental release from a nuclear power plant. 60 refs, 32 figs.

  16. 对战后初期美国转变对日政策原因的再审视%Revaluation of Causes for Changes in US Policy towards Japan in Early Post-war Period of WWⅡ

    Institute of Scientific and Technical Information of China (English)

    张经纬

    2016-01-01

    The changes in the relations between US and Japan after WWII had been the major element af-fecting the stability of Eastern Asian region.The focus of United State’s policy towards Japan at the early post-war period of WWII experienced a transition process from transforming to supporting.The transition had a complicated historical background and reason,went through a tortuous transformation process.The direct result set a base for the following US-Japan relationship and now has a major effect upon changes in the international political structure of Eastern Asian region.Those elements affected US to change its policy towards Japan in the early years after WWII are not so important as analyzed by those Chinese and foreign scholars,but all of which have a logical connections,some coming first,other following afterwards,or some being primary and other being secondary and finally leading to the formation of the “San Francisco Sys-tem”.In the process of changes in US policy towards Japan,disputes in ideology and gambles on national interests between US and the Soviet Union interacted honestly and straightforwardly,sometimes agreed with each other,sometimes departed from each other,aiming at their own individual national interests.All of these are important references for predicting the trends of the current international political structure of Eastern Asian region,and for the fundamental key and policies in correctly dealing with international af-fairs of that region.%战后美日关系的变动,始终是影响东亚地区稳定的重要因素。战后初期美国对日政策的重心经历了从改造到扶持的转变过程。这一转变有着复杂的历史背景和原因,经历了曲折的转变过程,转变的直接结果奠定了之后的美日关系,且至今仍对东亚地区国际政治格局的变化存在着重要影响。战后初期影响美国转变对日政策的诸因素,并非先前中外学者所分析的平行并重,而是有先有

  17. Early clerkships

    NARCIS (Netherlands)

    Kamalski, Digna M. A.; Ter Braak, Edith W. M. T.; Ten Cate, Olle Th. J.; Borleffs, Jan C. C.

    2007-01-01

    Background: Early clinical experience is being introduced in innovative, vertically integrated undergraduate medical curricula. While in many cases, this early clinical experience is limited to the presence of patients during lectures, in Utrecht students gain 'hands on' experience of daily clinical

  18. FEATURES OF A COURSE OF THE INFECTION CAUSED BY A VIRUS OF HERPES OF THE 6TH TYPE AMONG CHILDREN OF EARLY AGE IN THE SETTING OF A ACUTE RESPIRATORY VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    N. V. Okolysheva

    2014-01-01

    Full Text Available We examined 95 children aged from 5 months till 3 years (middle age 1,7 ±1,1, who were admitted in children's infectious department of theClinicalInfectionsHospital№1 by diagnosis acute respiratory virus infection in the height of disease. Anti-genes of sharp respiratory viruses by the IF method, markers of HHV-6 type, and also a cytomegalovirus of the person (CMV and Epstein-Barre's virus the ELISA methods and PTsR-rv are studied. Respiratory viruses are found among the hospitalized children in 46,3% of cases, from them paraflu (32,6% in comparison with flu (9,5% and a respiratornosintsitialny virus (4,2%, р < 0,05 statistically significantly is more often revealed. Markers of HHV are revealed at 73,7% of children. During the mixed infection HHV-6 markers are found in the vast majority of children (79,4% in combination with this or that representative of Herpesviridae, is statistically significantly more often with CMV(16,8%, р < 0,05. DNA of HHV-6 is statistically significantly more often (41% and with more viral load (53 400 copies/ml is revealed in a saliva in comparison with blood and urine. DNA of HHV-6 ina saliva statistically significantly is defined among the children visiting child care centers more often, than at unorganized children (72% against 40,4%, р = 0,0001 that testifies about a horizontal transmission of infection. It is observed that markers of HHV-6 are defined statistically significantly more often among children aged from 7 till 12 months (50% and among children older by 1 year (49,2% in comparison with children aged from 0 till 6 months (10%, р < 0,05. It is shown that among children of an early age the exanthema at HHV-6-of an infection is associated with presence of DNA of HHV-6 with high concentration (more than 120 000 copies/ml in blood.

  19. Early-phase of Clinical Phenomenon of Diabetes Caused by Clozapine in the Treatment of Schizophrenia%氯氮平治疗精神分裂症时引发糖尿病的前期临床特点

    Institute of Scientific and Technical Information of China (English)

    岳卫清; 姚明荣; 曹明; 袁天懿; 查显友; 夏江明

    2011-01-01

    目的 探讨抗精神病药物氯氮平引发糖尿病之前的临床特点.方法 采用临床开放研究,单一服用抗精神病药物氯氮平患者82例,每个月测定空腹血糖、餐后2 h血糖、三酰甘油(TG)、胆固醇(TC)、体质量、身高,计算体质量指数(BMI),采用国际体力活动短问卷(IPAQ-SF)评估患者的体力活动水平.观察1 a,发现糖尿病患者22例(糖尿病组),其余为未患糖尿病组60例,以发现糖尿病或研究结束为基线,对两组患者的相关监测指标进行分析.结果 糖尿病组和未患糖尿病组患者TG分别为2.95~3.94,1.93~2.31 mol·L-1,BMI分别为24.78~26.30,22.91~23.67(P<0.01);糖尿病组患者体力活动水平低于未患糖尿病组(P<0.01).结论 氯氮平引发糖尿病之前1 a就存在TG、BMI与体力活动水平的异常.%Objective To study the clinical features before development of diabetes caused by clozapine. Methods The clinical open surveys were used in 82 patients with schizophrenics who were given with clozapine only. The fasting plasma glucose,2 hours postprandial blood glucose, triglyceride( TG ), blood cholesterol( TC ), body weight, height, body mass index ( BMI ) were tested every month. The international physical activity questionnaire short form( IPAQ-SF ) was used to assess these patients' physical activity level. After one year follow-up ,22 patients were diagnosed as diabetes. The diagnosed diabetes or the end of study was regarded as baseline. the investigated indicators were analyzed. Results Triglyceride and BMI in both diabetes groups were 2.95 -3.94,1.93 -2.31 mol · L-1 and 24.78 -26.30,22.91-23.67, respectively( P<0.01 ), physical activity of the diabetes group was lower than that of the non-diabetes group( P<0.01 ). Conclusion Triglyceride, BMI and physical activity level were abnormal 1 a before diabetes caused by clozapine.

  20. What Causes Thyroid Cancer?

    Science.gov (United States)

    ... Cancer Causes, Risk Factors, and Prevention What Causes Thyroid Cancer? Thyroid cancer is linked with a number of ... inside a cell, without an outside cause. Papillary thyroid cancer Several DNA mutations (changes) have been found in ...

  1. What Causes a Toothache?

    Science.gov (United States)

    ... directly to your desktop! more... What Causes a Toothache? Article Chapters What Causes a Toothache? Why Does ... bite. Tooth eruption may be the cause of tooth or jaw pain in babies and school-age children. TMJ, sinus ...

  2. Early literacy

    DEFF Research Database (Denmark)

    Jensen, Anders Skriver

    2012-01-01

    This paper discusses findings from the Danish contribution to the EASE project, a European research project running from 2008 to 2010 on early literacy in relation to the transition from childcare to school. It explores a holistic, inclusive approach to early literacy that resists a narrow...... and schools. The paper also draws on Gee’s (2001, 2003, 2004, 2008) sociocultural approach to literacy, and Honneth’s (2003, 2006) concept of recognition. Emphasizing participation and recognition as key elements, it claims that stakeholders in early liter- acy must pay attention to how diverse early literacy...... opportunities empower children, especially when these opportunities are employed in a project-based learning environ- ment in which each child is able to contribute to the shared literacy events....

  3. Oestrus ovis as a cause of red eye in Aljabal Algharbi, Libya

    Directory of Open Access Journals (Sweden)

    Manal Z.M Abdellatif

    2011-01-01

    Conclusion : External ophthalmomyiasis caused by Oestrus ovis can cause red eye in patients from Aljabal Algharbi, Libya and requires careful examination to ensure early diagnosis and proper treatment.

  4. Feasibility research on early rehabilitation therapy for glenohumeral subluxation caused by stroke hemiplegia%早期康复治疗在脑卒中偏瘫所致肩关节半脱位中的可行性研究

    Institute of Scientific and Technical Information of China (English)

    鲍杨东

    2014-01-01

    目的:探讨早期康复治疗在脑卒中偏瘫所致肩关节半脱位中的临床疗效。方法80例脑卒中偏瘫所致肩关节半脱位患者,随机分为对照组和观察组,对照组给予常规药物治疗,观察组在常规药物治疗的基础上给予早期康复治疗,比较两组患者治疗总有效率的差异。结果观察组治疗总有效率为95.0%,显著高于对照组的65.0%(P<0.05)。结论在脑卒中偏瘫所致肩关节半脱位患者中应用早期康复治疗效果确切,可有效预防二次性损伤及废用综合征,促进肩关节半脱位的功能恢复,值得临床广泛推广使用。%Objective To investigate the clinical effect of early rehabilitation therapy for shoulder glenohumeral subluxation caused by stroke hemiplegia. Methods A total of 80 cases of glenohumeral subluxation patients caused by stroke hemiplegia randomly were divided into control group and observation group. The control group received conventional medical treatment and the observation group was given early rehabilitation therapy based on conventional medical treatment. The total effective rates of two groups were compared. Results The total effective rate of the observation group was 95.0%, which was significantly higher than the control group’s 65.0%(P<0.05). Conclusion Early rehabilitation therapy has exact effect on glenohumeral subluxation caused by stroke hemiplegia and can prevent secondary injury and disuse syndrome. It will promote the function recovery after glenohumeral subluxation and be worthy of clinical promotion.

  5. What Causes Bronchitis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Bronchitis? Acute Bronchitis Infections or lung irritants cause acute bronchitis. The ... fire, also may lead to acute bronchitis. Chronic Bronchitis Repeatedly breathing in fumes that irritate and damage ...

  6. What Causes Lactose Intolerance?

    Science.gov (United States)

    ... Information Clinical Trials Resources and Publications What causes lactose intolerance? Skip sharing on social media links Share ... lactase in the body is the cause of lactose intolerance. The names for the three types of ...

  7. Causes of Pediatric Cardiomyopathy

    Science.gov (United States)

    Search ABOUT THE DISEASE CAUSES Although pediatric cardiomyopathy is one of the leading causes of cardiac death in children, an explanation for why it occurs remains unknown. Most cases are familial ...

  8. What Causes Cardiomyopathy?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Cardiomyopathy? Cardiomyopathy can be acquired or inherited. “Acquired” means ... case when the disease occurs in children. Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy usually is inherited. It’s caused by ...

  9. What Causes Menstrual Irregularities?

    Science.gov (United States)

    ... Publications What causes menstrual irregularities? Skip sharing on social media links Share this: Page Content Menstrual irregularities can be caused by a variety of conditions, including pregnancy, hormonal imbalances, infections, malignancies, diseases, trauma, and certain ...

  10. What Causes Atherosclerosis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  11. What Causes Anemia?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Anemia? The three main causes of anemia are: Blood ... the blood and can lead to anemia. Aplastic Anemia Some infants are born without the ability to ...

  12. What Causes Cystic Fibrosis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  13. What Causes Sarcoidosis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Sarcoidosis? The cause of sarcoidosis isn't known. More ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  14. What Causes Down Syndrome?

    Science.gov (United States)

    ... Information Clinical Trials Resources and Publications What causes Down syndrome? Skip sharing on social media links Share this: ... Down Syndrome Registry​ . Chromosomal Changes That Can Cause Down Syndrome Research shows that three types of chromosomal changes ...

  15. Causes of High Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Causes of High Cholesterol Updated:Jul 5,2017 If you have high ... and procedures related to heart disease and stroke. Cholesterol • Home • About Cholesterol • HDL, LDL, and Triglycerides • Causes ...

  16. Incidence Causes and Outcome

    African Journals Online (AJOL)

    GB

    causes and outcome of obstructed labor in Jimma University Specialized Hospital. METHODS: ... Obstructed labor is an important cause of ... and outcome on the mother and baby. Data .... to this hospital after onset of labor as compared to the.

  17. Similar causes of various reproductive disorders in early life

    Directory of Open Access Journals (Sweden)

    Konstantin Svechnikov

    2014-02-01

    Full Text Available During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals (EDCs, due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted.

  18. Severe early onset osteopenia and osteoporosis caused by antiepileptic drugs.

    NARCIS (Netherlands)

    Beerhorst, K.; Huvers, F.C.; Renier, W.O.

    2005-01-01

    We describe two adult patients with epilepsy who received long-term antiepileptic drug therapy, a woman aged 39 years and a man aged 38 years, in whom severe osteopenia and osteoporosis, respectively, were diagnosed. Both had had epilepsy since childhood, both were seizure free and off medication

  19. Submental thyroid ectopy might cause subclinical hypothyroidism in early childhood

    Directory of Open Access Journals (Sweden)

    Mirjana Kocova

    2016-12-01

    Full Text Available Objective: Thyroid ectopy is a rare condition resulting from abnormal embryologic development and migration of the gland. Sublingual is the most common thyroid ectopy; all other ectopic thyroid locations occur very rare. There are no reports in the literature that describe the clinical course of patients with congenital hypothyroidism due to thyroid ectopy. Methods and Results: We present a child with congenital hypothyroidism detected on neonatal screening which had a subclinical course during follow-up. Scintigraphy revealed submental thyroid ectopy, a rare ectopic location and no orthotopic thyroid gland. Conclusion: Our case is unique because of the rare ectopic thyroid location but also of the unexpected clinical course; however, further thyroid monitoring is required for the therapy adjustment and detection of any changes in the ectopic tissue.

  20. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    DEFF Research Database (Denmark)

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L

    2015-01-01

    : All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20...... for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients' fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. RESULTS...... alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved...

  1. Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012).

    Science.gov (United States)

    Kawabata, Hiroshi; Takai, Kazue; Kojima, Masaru; Nakamura, Naoya; Aoki, Sadao; Nakamura, Shigeo; Kinoshita, Tomohiro; Masaki, Yasufumi

    2013-01-01

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  2. What Causes Heart Disease?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Heart Disease? Research suggests that coronary heart disease (CHD) begins with damage to the lining and ... causing coronary microvascular disease (MVD). Coronary MVD is heart disease that affects the heart's tiny arteries. The cause ...

  3. NGIPS Early Design Space Assessment

    Science.gov (United States)

    2014-07-17

    cycles). The results of this case are shown in Fig. 4. It can be seen that the fault causes a momentary outage of some loads and that the system...perform shipboard power system performance metric refinements, early- stage assessment computational tool investigation, and the application of these...early-stage design space exploration methods and tools were pursued in support of the Navy’s Next Generation Integrated Power Systems (NGIPS

  4. Causes and effects.

    Science.gov (United States)

    Cone, Carol L; Feldman, Mark A; DaSilva, Alison T

    2003-07-01

    Most companies make charitable donations, but few approach their contributions with an eye toward enhancing their brands. Those that do take such an approach commit talent and know-how, not just dollars, to a pressing but carefully chosen social need and then tell the world about the cause and their service to it. Through the association, both the business and the cause benefit in ways they could not otherwise. Organizations such as Avon, ConAgra Foods, and Chevrolet have recognized that a sustained cause-branding program can improve their reputations, boost their employees' morale, strengthen relations with business partners, and drive sales. And the targeted causes receive far more money than they could have from direct corporate gifts alone. The authors examine these best practices and offer four principles for building successful cause-branding programs. First, they say, a company should select a cause that advances its corporate goals. That is, unless the competitive logic for supporting the cause is clear, a company shouldn't even consider putting its finite resources behind it. Second, a business should commit to a cause before picking its charitable partners. Otherwise, a cause-branding program may become too dependent on its partners. Third, a company should put all its assets to work, especially its employees. It should leverage the professional skills of its workers as well as its other assets such as distribution networks. And fourth, a company should promote its philanthropic initiatives through every possible channel. In addition to using the media, it should communicate its efforts through the Web, annual reports, direct mail, and so on. Cause branding is a way to turn the obligations of corporate citizenship into a valuable asset. When the cause is well chosen, the commitment genuine, and the program well executed, the cause helps the company, and the company helps the cause.

  5. Observation on the Effect of Early Puncture Drainage in the Treatment of Patients with Intracranial Hemorrhage Caused by Delayed Vitamin K1 Deficiency%早期穿刺引流在迟发维生素K1缺乏致颅内出血中的疗效观察

    Institute of Scientific and Technical Information of China (English)

    栾劲; 杨皎莹

    2014-01-01

    目的:观察早期穿刺引流在迟发维生素K1缺乏致颅内出血中的疗效。方法:选取2010年1月-2013年4月于本院进行常规治疗的27例迟发维生素K1缺乏致颅内出血患儿为对照组,27例进行早期穿刺引流治疗的患儿为观察组,然后将两组患儿的治疗总有效率、出血停止时间、住院时间、并发症发生率及不同时间的NABA评分进行比较。结果:观察组患儿的治疗总有效率高于对照组,出血停止时间及住院时间均短于对照组,并发症发生率低于对照组,不同时间的NABA评分均优于对照组,差异均有统计学意义( P<0.05)。结论:早期穿刺引流在迟发维生素K1缺乏致颅内出血中的疗效较好,可有效改善患儿的预后。%Objective:To observe the effect of early puncture drainage in the treatment of patients with intracranial hemorrhage caused by delayed vitamin K1 deficiency.Method:27 newborns with intracranial hemorrhage caused by delayed vitamin K1 deficiency who were treated with routine treatment in our hospital from January 2010 to April 2013 were the control group,27 cases who were treated with early puncture drainage were the observation group,then the total effective rate,stopping time of bleeding,hospitalization time,rate of complications and NABA score at different time of two groups were compared.Result:The total effective rate of observation group was higher than that of control group,stopping time of bleeding and hospitalization time were shorter than those of control group,rate of complications was lower than that of control group,ABA score at different time were better than those of control group,there were all significant differences(P<0.05).Conclusion:The effect of early puncture drainage in the treatment of patients with intracranial hemorrhage caused by delayed vitamin K1 deficiency is better,and it can effectively improve the prognosis of newborns.

  6. 对交通意外骨伤患者早期应用积极心理干预的临床研究%The clinical research of early positive psychological intervention on the fracture patient caused by traffic accident

    Institute of Scientific and Technical Information of China (English)

    管正通; 何少波; 宫本宏; 罗献明

    2015-01-01

    ObjectiveThe early positive psychological intervention on the fracture patient with various of surgical treatments caused by the traffic accident could slow down the progress of psychological problems, promote the recovery and improve the degree of treatment satisfaction.Methods100 pationts with fracture caused by the traffic accident were randomly diveded into two groups,each group 50 named treatment group and control group. In the treatment group, 24 hours after hospitalized when the condition stabilized, the interview methods of HAMA and HAMD were tested and immediately the measure of early positive psychological intervention were taken.ResultsThe patients in intervention group had less anxiety and depression the former`s scale score (P<0.01).ConclusionThe early positive psychological intervention on the fracture patients with surgical operation caused by traffic accident could slow down the negative emotions of anxiety and depression, help patients to keep a good state of body and mind.%目的:通过对交通意外所致的各种需要手术治疗的的骨折患者进行早期积极的心理干预,以降低患者各种心理问题的发生发展,促进疾病的康复,提高治疗满意度,使医患关系更和谐。方法在骨科病房中分两组医生,每组中按随机分配方法各选取上述病情患者50例,分为干预组和对照组。对干预组患者在入院病情稳定后24小时内采用固定访谈法给予汉密尔顿焦虑量表(HAMA)和汉密尔顿抑郁量表(HAMD)测验后即刻采取积极有效的心理干预措施。结果经干预后,干预组患者的焦虑和抑郁均较对照组有明显好转,其量表分对比明显下降,经统计学检测P<0.001,有明显意义。结论通过早期积极的心理干预可以较低各种交通意外骨折需手术患者的焦虑、抑郁等负面情绪,帮助其保持良好的身心状态,促进骨折康复,提高满意度,能使医患关系更和谐。

  7. CAUSES OF OCCUPATIONAL INJURIES

    NARCIS (Netherlands)

    KINGMA, J

    1994-01-01

    The causes of occupational injuries (N = 2,365) were investigated. Accidents with machinery and hand tools were the two main causes (49.9%). 89% of the patients with occupational injuries were male. The highest risk group were in the age category of 19 years or less (51.9%). This age group also show

  8. Empyema caused by trichomonas.

    Science.gov (United States)

    Lewis, Kevin L; Doherty, Dennis E; Ribes, Julie; Seabolt, John P; Bensadoun, Eric S

    2003-01-01

    Empyema is one of the potential complications of lower respiratory tract infections. Very rarely, in predisposed individuals, empyema can be caused by Trichomonas species, of which Trichomonas tenax appears to be the most common cause. Here, we present a case of trichomonal empyema in a 56-year-old man and review the available literature of this rare occurrence.

  9. Causes of Child Abuse

    OpenAIRE

    Deveci,S.Erhan; Açık, Yasemin

    2014-01-01

    Child abuse is an important public health problem that is present almost in every society and environment at different level and intensities. For implementation of child abuse protection measures it is necessary to investigate its causes. In this review, causes of child abuse was attempted to investigate with respects to the society and institution, family and individual and child related factors.

  10. Causes of Paralysis

    Science.gov (United States)

    ... is caused by a virus that attacks the nerves which control motor function. > Spina bifida A neural tube defect that causes incomplete closure in the spinal column. > Spinal cord injury Involves damage to the nerves within the bony protection of the spinal canal. > ...

  11. Do Allergies Cause Asthma?

    Science.gov (United States)

    ... Happens in the Operating Room? Do Allergies Cause Asthma? KidsHealth > For Kids > Do Allergies Cause Asthma? A A A en español ¿Las alergias provocan ... kinds of allergies are more likely to have asthma. Do you have allergies that affect your nose ...

  12. What Causes Bad Breath?

    Science.gov (United States)

    ... A Week of Healthy Breakfasts Shyness What Causes Bad Breath? KidsHealth > For Teens > What Causes Bad Breath? A A A en español ¿Qué es lo que provoca el mal aliento? Bad breath, or halitosis , can be a major problem, ...

  13. What Causes Raynaud's?

    Science.gov (United States)

    ... primary and secondary. In primary Raynaud’s (also called Raynaud’s disease), the cause isn't known. Primary Raynaud's is ... examples of diseases and conditions that can cause Raynaud's include: Rheumatoid (RU-ma-toyd) ... (SHOW-gren's) syndrome, dermatomyositis (DER-ma-to-mi-o-SI-tis), ...

  14. Causes of Diabetes

    Science.gov (United States)

    ... iron can build up in and damage the pancreas and other organs. Hormonal diseases Some hormonal diseases cause the body to produce too much of certain hormones, which sometimes cause insulin resistance and diabetes. ... of the pancreas Pancreatitis , pancreatic cancer, and trauma can all harm ...

  15. Pyopneumopericardium caused by mediastinal granuloma.

    Science.gov (United States)

    Gula, Lorne J; Malthaner, Richard A; Quantz, Mackenzie A

    2002-07-01

    We report the case of a previously healthy 32-year-old man who was seen with flulike symptoms, dyspnea, and chest pain. The diagnosis was pyopneumopericardium, and pericardial tap revealed 1.3 L of purulent material. Computed tomography of the chest demonstrated a calcified mass inferior to the carina. Urgent exploration through a right thoracotomy revealed that the mass was adherent to the esophagus and pericardium. The subcarinal mass was resected. Pathological study demonstrated granulomatous lymph nodes, which were likely due to histoplasmosis. This is among the first reports of granulomatous erosion into the pericardium causing pyopneumopericardium. The patient made a good recovery, and his case demonstrates the importance of early imaging and mediastinal exploration for pyopneumopericardium.

  16. Endocarditis caused by Abiotrophia defectiva

    Directory of Open Access Journals (Sweden)

    Asma M Al-Jasser

    2007-01-01

    Full Text Available A 35-year–old man with pre-existing rheumatic heart disease and aortic regurgitation (AR presented with intermittent fever, ankle swelling and clinical evidence of endocarditis. Transoesophageal echocardiogram (TEE revealed vegetations and destruction of the aortic valve (AV. Blood cultures grew a gram positive coccobacillus which was phenotypically identified as Abiotrophia defectvia (A.defectiva. A diagnosis of infective endocarditis (IE due to A.defectiva was made. Treatment, with penicillin and gentamicin, was administered for 4 weeks. Mechanical valve replacement was required few days after starting the antibiotic therapy. The patient had a favorable outcome on follow up.Although A.defectiva is an uncommon cause of endocarditis, early and correct identification of this pathogen is important to improve the outcome and the prognosis of patients with IE due to this organism.

  17. Causes of secondary pediatric osteoporosis.

    Science.gov (United States)

    Bianchi, Maria Luisa

    2013-06-01

    Secondary osteoporosis is increasingly observed in both adult and pediatric patients affected by many heterogeneous diseases. Most forms of secondary osteoporosis derive from one or more of the following causes: malnutrition, malabsorption, immobilization and/or reduced mechanical load, vitamin D deficiency, chronic inflammation, hormonal derangements, and chronic use of glucocorticoids and other drugs. Considering the lack of symptoms in the early phases, both the risk and the presence of secondary osteoporosis tend to be underestimated, and as a consequence, appropriate prevention/treatment measures are often delayed or not taken at all. Failure to accumulate an appropriate bone mass for gender and age or to build an architecturally "strong" bone must always be suspected when a child or adolescent presents with frequent and/or low-trauma fractures, chronic bone pain, or an incidental finding of "osteopenia" on plain X-rays. Known risk factors must always be considered.

  18. Ethics dilemmas of early detection of obesity

    DEFF Research Database (Denmark)

    Vallgårda, Signild

    2016-01-01

    Aim: To discuss the ethics dilemmas of the early detection of overweight and obesity. Methods: Analysis of the ethical aspects of early detection. Results: The early detection of overweight and obesity entails a number of ethical dilemmas because it may both be helpful and harmful. It may help...... people to lead a healthier life and non-detection could be considered neglectful. It may, however, cause anxiety, interfere with people’s integrity, focus only on individual causes and responsibilities, cause stigmatization and have adverse effects by inducing weight gain. Conclusions: Documentation...

  19. Childhood Obesity Causes & Consequences

    Science.gov (United States)

    ... to Prevent Obesity Early Care and Education State Indicator Report Salad Bars to School Healthy Food Service ... Healthy Hospital Practice to Practice Series (P2P) Healthy Hospital Tool ... and implications for diagnosis and management in primary care. Exp Biol Med (Maywood). 2014; ...

  20. What Causes COPD?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes COPD? Long-term exposure to lung irritants that damage ... Rate This Content: NEXT >> Featured Video What is COPD? 05/22/2014 Describes how COPD, or chronic ...

  1. Can Lupus Cause Depression?

    Science.gov (United States)

    ... lupus Living well with lupus Can lupus cause depression? Life with lupus can be challenging. With symptoms ... treatable illness called clinical depression. Symptoms of Clinical Depression People are considered clinically depressed when they have ...

  2. What Causes Thalassemias?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Thalassemias? Your body makes three types of blood cells: ... have inherited faulty genes from both parents. Alpha Thalassemias You need four genes (two from each parent) ...

  3. Viral causes of diarrhea.

    Science.gov (United States)

    Goodgame, R W

    2001-09-01

    Viruses are important causes of diarrhea. In healthy adults, the main clinical manifestation is acute, self-limited gastroenteritis. Advances in molecular diagnostics have shown that epidemics of acute gastroenteritis most frequently are due to caliciviruses spread through contaminated food or through person-to-person contact. Application of similar technology is needed to make a definitive statement about the role of such candidate viruses as rotavirus, astrovirus, and adenovirus as the cause of nonepidemic acute gastroenteritis in adults. Rarely a previously healthy adult gets acute CMV colitis. CMV and EBV mainly cause diarrhea in immunocompromised patients, however. Advances in prophylaxis and treatment have reduced the frequency and severity of these diseases. Acute infantile gastroenteritis is caused by rotavirus, calcivirus, astrovirus, and adenovirus. These viral diseases of the gut are seen by the physician as routine and rare clinical problems.

  4. What Causes Polycythemia Vera?

    Science.gov (United States)

    ... body to make more of the hormone erythropoietin (EPO). High levels of EPO can prompt your body to make more red ... secondary polycythemia. Rarely, tumors can make and release EPO, or certain blood problems can cause the body ...

  5. Causes of Ataxia

    Science.gov (United States)

    ... Donate to the National Ataxia Foundation Causes of Ataxia The hereditary ataxias are genetic, which means they ... the disease is inherited as a recessive gene. Ataxia Gene Identified in 1993 The first ataxia gene ...

  6. What Causes Hemophilia?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Hemophilia? A defect in one of the genes that ... the hemophilia gene is inherited. Inheritance Pattern for Hemophilia—Example 1 The image shows one example of ...

  7. Early Astronomy

    Science.gov (United States)

    Thurston, Hugh

    The earliest investigations that can be called scientific are concerned with the sky: they are the beginnings of astronomy. Many early civilizations produced astronomical texts, and several cultures that left no written records left monuments and artifacts-ranging from rock paintings to Stonehenge-that show a clear interest in astronomy. Civilizations in China, Mesopotamia, India and Greece had highly developed astronomies, and the astronomy of the Mayas was by no means negligible. Greek astronomy, as developed by the medieval Arab philosophers, evolved into the astronomy of Copernicus. This displaced the earth from the central stationary position that almost all earlier astronomies had assumed. Soon thereafter, in the first decades of the seventeenth century, Kepler found the true shape of the planetary orbits and Galileo introduced the telescope for astronomical observations.

  8. Rare causes of osteoporosis

    OpenAIRE

    Marcucci, Gemma; Brandi, Maria Luisa

    2015-01-01

    Osteoporosis is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. It is classically divided into primary (post-menopausal or senile), secondary and idiopathic forms. There are many rare diseases, that cause directly or indirectly osteoporosis. The identification and classification of most of these rare causes of osteoporosis is crucial for the specialists in endocrinology and not, in order to prevent this bone complication and ...

  9. Occupational asthma caused by palladium

    Energy Technology Data Exchange (ETDEWEB)

    Daenen, M.; Rochette, F.; Demedts, M.; Nemery, B. [K.U. Leuven, Pneumology (Belgium); Rogiers, P. [A.Z. St-Lucas, Brugge (Belgium); Walle, C. Van de [Siemens, Oostkamp (Belgium)

    1999-01-01

    Occupational exposure to complex platinum salts is a well-known cause of occupational asthma. Although there is evidence that platinum refinery workers may also be sensitized to other precious metals, such as palladium or rhodium, no instances of occupational asthma due to an isolated sensitization to palladium have been reported. A case is reported of occupational rhinoconjunctivitis and asthma in a previously healthy worker exposed to the fumes of an electroplating bath containing palladium. There was no exposure to platinum. Sensitization to palladium was documented by skin-prick tests. The skin-prick test was positive with Pd(NH{sub 3}){sub 4}Cl{sub 2}, but not with (NH{sub 4}){sub 2}PdCl{sub 4}. Corresponding salts of platinum were all negative. A bronchial provocation test with Pd(NH{sub 34})Cl{sub 2} (0.0001 % for a total of 315 s, followed by 0.001 % for a total of 210 s) led to an early decrease in forced expiratory volume in one second (-35%). A similar exposure (0.001 % for a total of 16 min) in an unrelated asthmatic gave no reaction. This case shows that an isolated sensitization to palladium can occur and that respiratory exposure to palladium is a novel cause of metal-induced occupational asthma. (au) 24 refs.

  10. Pantoea dispersa: an unusual cause of neonatal sepsis.

    Science.gov (United States)

    Mehar, Veerendra; Yadav, Dinesh; Sanghvi, Jyoti; Gupta, Nidhi; Singh, Kuldeep

    2013-01-01

    Neonatal septicemia is the most important cause of neonatal mortality. A wide variety of bacteria both aerobic and anaerobic can cause neonatal sepsis. Genus Pantoea is a member of Enterobacteriaceae family that inhabits plants, soil and water and rarely causes human infections, however, Pantoea dispersa has not been reported as a causative organism for neonatal sepsis. We hereby report two neonates with early onset sepsis caused by Pantoea dispersa. Early detection and appropriate antibiotic therapy can improve overall outcome of this rare infection in neonates. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  11. Pantoea dispersa: an unusual cause of neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Veerendra Mehar

    Full Text Available Neonatal septicemia is the most important cause of neonatal mortality. A wide variety of bacteria both aerobic and anaerobic can cause neonatal sepsis. Genus Pantoea is a member of Enterobacteriaceae family that inhabits plants, soil and water and rarely causes human infections, however, Pantoea dispersa has not been reported as a causative organism for neonatal sepsis. We hereby report two neonates with early onset sepsis caused by Pantoea dispersa. Early detection and appropriate antibiotic therapy can improve overall outcome of this rare infection in neonates.

  12. Maternal mortality: analysis of causes and preventable factors

    Directory of Open Access Journals (Sweden)

    K. P. Mohana Sundari

    2016-06-01

    Conclusions: Hypertensive disorder pregnancy was found to be the direct major causes of death. Although booking level is high, health education of women, early identification of PIH and its management, early identification of anaemia and prompt correction, early referral, judicious use of IV fluids, blood products and drugs can prevent more than 90% of maternal deaths. [Int J Reprod Contracept Obstet Gynecol 2016; 5(6.000: 1719-1721

  13. Causes of vertigo

    Directory of Open Access Journals (Sweden)

    Violetta Aleksandrovna Tolmacheva

    2010-01-01

    Full Text Available Vertigo is the second common complaint next to headache, which makes a patient seek medical care. Neurological, auricular, cardiac, mental, and other diseases may be a cause of dizziness. Since vertigo is interdisciplinary in nature, there are frequently problems of establishing its origin. Vertigo is commonly associated with vascular pathology of the head and neck, which results in the hyperdiagnosis of cerebrovascular diseases. At the same time, little attention is given to the patient's psychoemotional sphere and ENT pathology. Large-scale studies have demonstrated that vertigo most frequently results from psychogenic causes and vestibular apparatus diseases.

  14. Darwin's Sacred Cause

    DEFF Research Database (Denmark)

    2009-01-01

    of scholarly specialists and been appropriated by money makers. One could not help thinking about this as, in the autumn of 2008, the publisher began hyping Darwin's Sacred Cause as ‘one of the major contributions to the worldwide Darwin anniversary celebrations in 2009' Udgivelsesdato: February...

  15. Causes, Treatments and Consequences

    African Journals Online (AJOL)

    groups in Africa. All Yoruba ... and Oduduwa as the founder of their race. Al- ... and with the various members of staff in a .... in the womb, and causes a lot of pain and sorrow ... have given up, God can still make you conceive, ... I was careless when I did my second abortion. ..... who feel embarrassed to walk around with an.

  16. Infestation caused by acanthocephala

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2009-03-01

    Full Text Available An on-line case of infestation caused by M. moniliformis is descripted. This rodents’ worm, belonging to acanthocephala, can be rarely responsible of human intestinal pathology. The case is the pretext for a brief revision on this parasitosis. So, biological, epidemiological, clinical and diagnostical findings are reported.

  17. Anaphylaxis caused by banana.

    Science.gov (United States)

    Savonius, B; Kanerva, L

    1993-04-01

    An anaphylactic reaction following ingestion of banana occurred in a 32-year-old female cook. The sensitization to banana occurred simultaneously with the development of occupational asthma caused by grain flour. The patient was sensitized to a wide range of airborne and ingestible proteins but not to rubber latex.

  18. Early diagnosis and early intervention in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Mijna eHadders-Algra

    2014-09-01

    Full Text Available This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP. CP describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to disturbances that occurred in the fetal or infant brain. Therefore the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions, but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuro-imaging techniques and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group best prediction is achieved with the combination of neuro-imaging and the assessment of general movements, in the latter group best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high risk infants without CP. In these infants early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is

  19. Causes of early deep venous thrombosis after posterior lumbar interbody fusion and the nursing strategies%后路腰椎椎间融合术后早期并发深静脉血栓形成的原因分析及护理

    Institute of Scientific and Technical Information of China (English)

    赵文雅; 林爱仙

    2011-01-01

    目的 探讨后路腰椎椎间融合术(Posterior lumbar interbody fusion,PLIF)后早期并发深静脉血栓(deep venous thrombosis,DVT)形成的原因与护理方法.方法 针对存在危险因素,术前全面评估,制订预防DVT发生护理措施,主要是肢体功能锻练及预防性抗凝治疗的护理.结果 9例DVT患者,经严密观察与护理,出院后随访6-12个月,未发生1例肺栓塞及其他相关并发症.结论 对深静脉血栓危险因素进行评估,加强对PLIF术后DVT症状的观察,同时采用综合有效护理措施,对降低DVT的发生具有积极的意义.%Objective Ta explore the causes of early deep venous thmmhosis (DVT) after posterior lumhar interbody fusion (PLIF).Methods 232 patients undergoing PLIF were involved in thia study from October 2000 to August 2009.Before PLIF, the preventive nursing strategies on DVT were formulated, focusing on function exercise of limbs and nursing care of preventive anticoagulation.Results Among all,9 cases developed with DVT and discharged after close management and nursing care.6 - 12 months follow-up witnessed no complications including pulmonay embolism.Conclusion It ia critical to lower the incidence of DVT by way of assessing the risk factors in DVT,enhancing observation on DVT after PLIF and taking nursing interventions.

  20. Reconstruction of Native Chieftain Political Orders and its Influence in Rgyalrong during the Early Qing Period---With Remarks on the Causes of the Jinchuan War%清初土司政治秩序在嘉绒地方的重建及其影响--兼论金川之役爆发的缘起

    Institute of Scientific and Technical Information of China (English)

    邹立波

    2016-01-01

    自雍正初年,清朝着手在藏东边地重建土司政治秩序,从制度层面强化对土司的常规性控制,重点规范各土司之间的关系。但是在土司政治新秩序中建构起来的中央王朝与土司地方的新型政治关系,同嘉绒土司历史上固有的政治传统存有相悖之处。当新秩序深入嘉绒地方后,土司立足于传统的政治观念选择接纳或抵制。基于此,金川之役缘起的阐释应置于中央王朝与嘉绒地方双重视角及其相互关系的长时段演变中重新思考。%The Qing court carried out the reconstruction of native chieftain political orders in eastern Tibet from the early period of Yongzheng. The new orders aimed at institutionally conventional control on chieftains by demilitarization, which focused on regulating the relationship of chieftains. But the new relationship between central government and chieftains was in contradiction with the political traditions in Rgyalrong. With the development of the reconstruction, chieftains accepted or rejected this relationship according to the traditional concept of political logics. So we should re-examine the causes of Jinchuan War from the dual perspectives of Qing and Rgyalrong and the evolution of their relationship in long periods.

  1. Causes of death in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Galle, T S; Juel, K; Bülow, S

    1999-01-01

    The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due...... to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer....

  2. [Causes of camptocormia].

    Science.gov (United States)

    Glocker, F X; Berninger, U G

    2013-08-01

    In this society with an ever increasing number of the elderly there is an increasing number of causes of a bent spine syndrome (camptocormia/dropped head syndrome). The causes include neurological, neuro-orthopedic, rheumatological and psychiatric disorders. Parkinson's disease, dystonia and neuromuscular diseases (motor neuron disease, myositis and muscular dystrophy) with weakness of the axial muscles may result in bent spine syndrome and is often combined with a dropped head. Disc herniation, hypertrophic spondylosis or pseudospondylolisthesis with spinal narrowing may lead to an abnormal flexion of the trunk. Ankylosing spondylitis can produce a disabling bent spine syndrome. Camptocormia may also be mimicked by osteoporotic fractures of the vertebral bones with wedge-shaped vertebrae. In some cases camptocormia is related to a psychogenic disorder.

  3. What Causes Lupus Flares?

    Science.gov (United States)

    Fernandez, David; Kirou, Kyriakos A

    2016-03-01

    Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, follows a chronic disease course, punctuated by flares. Disease flares often occur without apparent cause, perhaps from progressive inherent buildup of autoimmunity. However, there is evidence that certain environmental factors may trigger the disease. These include exposure to UV light, infections, certain hormones, and drugs which may activate the innate and adaptive immune system, resulting in inflammation, cytotoxic effects, and clinical symptoms. Uncontrolled disease flares, as well as their treatment, especially with glucocorticoids, can cause significant organ damage. Tight surveillance and timely control of lupus flares with judicial use of effective treatments to adequately suppress the excessive immune system activation are required to bring about long term remission of the disease. We hope that new clinical trials will soon offer additional effective and target-specific biologic treatments for SLE.

  4. Labor Informality: General Causes

    Directory of Open Access Journals (Sweden)

    Gustavo Sandoval Betancour

    2016-04-01

    Full Text Available The article examines the main causes of labor informality in order to verify the validity of classical theories that explain unemployment in market economies and its relationship to informality. Methodologically, the project was based, in the empirical part, on international statistics, comparing the evolution of labor market structure in a combined sample of highly industrialized countries and other less industrialized ones. Empirical evidence supports the conclusion that the classical economic theory of Marxist origin is inefficient to explain the causes of unemployment in contemporary market economies, as well as it fails to satisfactorily explain informality. On the contrary, we conclude that the theory in question is more relevant to explain informality in centrally planned economies where this phenomenon has been present even more significantly than in free market economies.

  5. Tracing Actual Causes

    Science.gov (United States)

    2016-08-08

    process described by the model. A signature S = 〈U ,V,R〉 specifies a set of endogenous variables (V), a set of exogenous vari- ables (U) and a range R(X...we need a language for modeling causal processes (circuits, sys- tems, etc.) that generate caused and causative events. Fol- lowing prior work on...causation [Halpern and Pearl, 2005; Halpern, 2015; Pearl, 2000], we model causal processes as structural equations, which we recap briefly. Variables A, B

  6. Anaerobic Digestion Foaming Causes

    OpenAIRE

    Ganidi, Nafsika

    2008-01-01

    Anaerobic digestion foaming has been encountered in several sewage treatment plants in the UK. Foaming has raised major concerns for the water utilities due to significant impacts on process efficiency and operational costs. Several foaming causes have been suggested over the past few years by researchers. However, the supporting experimental information is limited and in some cases site specific. The present report aimed to provide a better understanding of the anaerobic di...

  7. Shocks in the Early Universe.

    Science.gov (United States)

    Pen, Ue-Li; Turok, Neil

    2016-09-23

    We point out a surprising consequence of the usually assumed initial conditions for cosmological perturbations. Namely, a spectrum of Gaussian, linear, adiabatic, scalar, growing mode perturbations not only creates acoustic oscillations of the kind observed on very large scales today, it also leads to the production of shocks in the radiation fluid of the very early Universe. Shocks cause departures from local thermal equilibrium as well as create vorticity and gravitational waves. For a scale-invariant spectrum and standard model physics, shocks form for temperatures 1  GeVUniverse as early as 10^{-30}  sec after the big bang.

  8. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  9. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  10. [Causes of depression].

    Science.gov (United States)

    Fernández, Francisco Alonso

    2011-01-01

    This paper describes four nosological categories of depressive disorder according to the fundamental or prime cause: endogen depression, situative depression, psychogen depression and somatogen (also pharmacogen or addictive) depression. Recent advances in neurobiology provide the commun pathogenic mechanism distribuited in neurochemical, neuroendocrine and neuroinmune factors, with at the end a cellular and molecular sequence beyond the synapse. There is an increased risk of depression multiplied by three or four in the elderly, obese, unemployed and inmigrant and it is very frequent in terminally ill patients with a pervasive desire for death. Finally, eight personalized preventive guidelines enable to decrease the individual risk of depression in more than a fifty per cent.

  11. Homology and causes.

    Science.gov (United States)

    Van Valen, L M

    1982-09-01

    Homology is resemblance caused by a continuity of information. In biology it is a unified developmental phenomenon. Homologies among and within individuals intergrade in several ways, so historical homology cannot be separated sharply from repetitive homology. Nevertheless, the consequences of historical and repetitive homologies can be mutually contradictory. A detailed discussion of the rise and fall of the "premolar-analogy" theory of homologies of mammalian molar-tooth cusps exemplifies such a contradiction. All other hypotheses of historical homology which are based on repetitive homology, such as the foliar theory of the flower considered phyletically, are suspect.

  12. Iatrogenic causes of infertility.

    Science.gov (United States)

    Schoysman, R; Segal, L

    1990-01-01

    The Authors review the list of the iatrogenic causes of infertility. In their opinion the more delicate the structure, the more heavy the price paid to clumsy or erroneous investigation. Such eventual incompetence may lead to further damage of the already existing situation. The Authors however look at the future with relative optimism: incidents become rarer, specialists in gynecology and infertility pay more attention to the delicacy of genital structures and there is an encouraging tendency to refer to infertility specialists those cases who need adequate work-up of their condition.

  13. Chorea caused by toxins.

    Science.gov (United States)

    Miyasaki, Janis M

    2011-01-01

    Chorea is uncommonly caused by toxins. Anecdotal evidence from cases of toxin-induced chorea assists in our understanding of neurodegenerative diseases associated with chorea. Beginning in medieval Europe with ergotism and the "fire that twisted people," spanning to crack dancing in contemporary times and the coexistence of alcohol abuse with chorea, toxins may exert direct effects to enhance mesolimbic dopamine transmission or indirect effects through gamma-aminobutyric acid modulation. The following chapter will discuss toxins associated with chorea and the presumed pathophysiology underlying the movement disorders in these case series.

  14. Darwin's Sacred Cause

    DEFF Research Database (Denmark)

    2009-01-01

    As we are being flooded by Darwin lollipops, t-shirts, quills and stamps it is becoming increasingly difficult to be heard or seen in the commercialised celebration in 2009. Some are in the business for the science, but a lot are in it for profit. Accordingly, the Darwin industry has left the hands...... of scholarly specialists and been appropriated by money makers. One could not help thinking about this as, in the autumn of 2008, the publisher began hyping Darwin's Sacred Cause as ‘one of the major contributions to the worldwide Darwin anniversary celebrations in 2009' Udgivelsesdato: February...

  15. Diagnosing vascular causes of renal failure.

    Science.gov (United States)

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  16. Environmental causes of violence.

    Science.gov (United States)

    Carpenter, David O; Nevin, Rick

    2010-02-09

    Violent and anti-social behavior is usually attributed to social factors, including poverty, poor education, and family instability. There is also evidence that many forms of violent behavior are more frequent in individuals of lower IQ. The role of exposure to environmental contaminants has received little attention as a factor predisposing to violent behavior. However a number of environmental exposures are documented to result in a common pattern of neurobehavioral effects, including lowered IQ, shortened attention span, and increased frequency of antisocial behavior. This pattern is best described for children exposed to lead early in life, but a similar pattern is seen upon exposure to polychlorinated biphenyls and methyl mercury. Although not as extensively studied, similar decrements in IQ are seen upon exposure to arsenic and secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also associated with increased rates of conduct disorder and attention deficit hyperactivity. Recent evidence suggests that temporal trends in rates of violent crime in many nations are consistent with earlier preschool blood lead trends, with a lag of about 20 years. These ecologic correlations are consistent with many controlled studies suggesting that lead-exposed children suffer irreversible brain alterations that make them more likely to commit violent crimes as young adults. If this pattern is true for lead and other contaminants, the most effective way to fight crime may be to prevent exposure to these contaminants.

  17. The Climate of Early Mars

    Science.gov (United States)

    Wordsworth, Robin D.

    2016-06-01

    The nature of the early martian climate is one of the major unanswered questions of planetary science. Key challenges remain, but a new wave of orbital and in situ observations and improvements in climate modeling have led to significant advances over the past decade. Multiple lines of geologic evidence now point to an episodically warm surface during the late Noachian and early Hesperian periods 3-4 Ga. The low solar flux received by Mars in its first billion years and inefficiency of plausible greenhouse gases such as CO2 mean that the steady-state early martian climate was likely cold. A denser CO2 atmosphere would have caused adiabatic cooling of the surface and hence migration of water ice to the higher-altitude equatorial and southern regions of the planet. Transient warming caused melting of snow and ice deposits and a temporarily active hydrological cycle, leading to erosion of the valley networks and other fluvial features. Precise details of the warming mechanisms remain unclear, but impacts, volcanism, and orbital forcing all likely played an important role. The lack of evidence for glaciation across much of Mars's ancient terrain suggests the late Noachian surface water inventory was not sufficient to sustain a northern ocean. Though mainly inhospitable on the surface, early Mars may nonetheless have presented significant opportunities for the development of microbial life.

  18. Cervicogenic causes of vertigo.

    Science.gov (United States)

    Hain, Timothy C

    2015-02-01

    Herein we discuss the recent literature concerning cervicogenic vertigo including vertigo associated with rotational vertebral artery syndrome, as well as whiplash and degenerative disturbances of the cervical spine. We conclude with a summary of progress regarding diagnostic methods for cervicogenic vertigo. Several additional single case studies of the exceedingly rare rotational vertebral artery syndrome have been added to the literature over the last year. Concerning whiplash and degenerative disturbances of the cervical spine, four reviews were published concerning using physical therapy as treatment, and two reviews reported successful surgical management. Publications regarding diagnostic methodology remain few and unconvincing, but the cervical torsion test appears the most promising. Little progress has been made over the last year concerning cervicogenic vertigo. As neck disturbances combined with dizziness are commonly encountered in the clinic, the lack of a diagnostic test that establishes that a neck disturbance causes vertigo remains the critical problem that must be solved.

  19. [Cellulite - causes, prevention, treatment ].

    Science.gov (United States)

    Janda, Katarzyna; Tomikowska, Anna

    2014-01-01

    Cellulite is a multifactorial etiology ailment. It changes the skin topography by the formation of the skin surface's appearance, changes described as "orange peel". This prob- lem concerns 85-98% of women, and for them it is one of the most intolerable aesthetic imperfections. In the past few years the interest of scientists in this problem has clearly increased. Several theories on the pathophysiology of cel- lulite have been produced A number of different thera- peutic regimens have been developed using modern tech- nology. However, despite the many treatment options for cellulite, it is extremely important that patients should be aware that only multidirectional treatment can bring sat- isfactory results. The aim of this review was to describe the causes of cellulite, and its prevention and treatment.

  20. Examination of Early Blight Resistance Derived From S. Raphanifolium

    Science.gov (United States)

    Early blight of potato (Solanum tuberosum L.), caused by Alternaria solani is a major cause of economic losses in many potato growing regions. Growers and breeders are interested in the development of potato cultivars with resistance to early blight as a means to decrease usage of fungicide applica...

  1. Early Specialization in Youth Sport: A Biomechanical Perspective

    Science.gov (United States)

    Mattson, Jeffrey M.; Richards, Jim

    2010-01-01

    This article examines, from a biomechanical perspective, three issues related to early specialization: overuse injuries, the developmental aspects, and the performance aspects. It concludes that "there is no evidence that early specialization causes overuse injuries or hinders growth and maturation." At the same time, early specialization has…

  2. The causes of epistasis

    Science.gov (United States)

    de Visser, J. Arjan G. M.; Cooper, Tim F.; Elena, Santiago F.

    2011-01-01

    Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions—called epistasis—have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype–phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability. PMID:21976687

  3. Necrotizing fasciitis caused by group A streptococcus

    Directory of Open Access Journals (Sweden)

    Mikić Dragan

    2002-01-01

    Full Text Available The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region. Parenteral antibiotic, substitution and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue. The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment. He was released from the hospital as completely cured two months after the admission.

  4. Causes for "ghost" manifolds

    Science.gov (United States)

    Borok, S.; Goldfarb, I.; Gol'dshtein, V.

    2009-05-01

    ;71:359-82; Flockerzi D. Tutorial: intrinsic low-dimensional manifolds and slow attractors. Magdeburg: Max-Planck-Institut; 2001-2005. ; Flockerzi D, Heineken W. Comment on "Identification of low order manifolds: validating the algorithm of Maas and Pope". Chaos 1999;9:108-23; Flockerzi D, Heineken W. Comment on "Identification of low order manifolds: validating the algorithm of Maas and Pope". Chaos 2006;16:048101]. The present work studies the causes for the "ghost" manifolds appearance for the case of a two-dimensional singularly perturbed system.

  5. 不明原因早发性癫痫脑病62例临床特点及相关基因突变分析%Clinical features and gene mutations analysis in 62 children with early - onset epileptic encephalopathy of un-known causes

    Institute of Scientific and Technical Information of China (English)

    胡春辉; 王龙飞; 王华

    2016-01-01

    Objective To study the clinical features and gene mutations of early - onset epileptic encephalo-pathy(EOEE)of unknown causes and to identify pathogenic mutations of EOEE by next generation sequencing. Methods The clinical data of 62 cases diagnosed with unexplained EOEE between June 2013 and June 2015 were ob-tained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy - related genes,and Sanger sequencing was performed to verify the results and confirm the source of the parents,further to identify suspected pathogenic mutations of EOEE. Results Among 62 cases with unex-plained EOEE,37 cases(61% )were diagnosed as non - specific EOEE,17 cases(27% )with West syndrome,6 ca-ses(10% )with Dravet syndrome,1 case(1% )with Ohtahara syndrome,1 case(1% )with early myoclonic epileptic encephalopathy. The pathogenic mutations were not detected among 17 cases with West syndrome and the early myoclonic epileptic encephalopathy. Among 37 cases with non - specific EOEE,suspected pathogenic mutations were detected in 7 cases. Three cases of missense mutations for PCDH19 gene,1 case of frame - shift mutation and 1 case of splice site mutation for CDKL5 gene,1 case of denovo nonsense mutation for KCNQ2 gene,and 1 case of missense muta-tion for GRIN2A gene were detected. Among 6 children with Dravet syndrome,2 cases of frame - shift mutations and 1 case of missense mutation for SCN1A gene were detected,of which 2 cases were of frame - shift mutations,1 case was denovo mutation,1 case of missense mutation for SCN1A gene and 1 case of missense mutation for SCN1A combined with SCN9A gene were detected. One case of denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 cases with clinical seizures were under control,and 40 cases were out of control. Conclusions The clinical pheno-types for children with unexplained EOEE were varied. SCN1A,SCN9A,STXBP1,PCDH19,CDKL5,KCNQ2 and GRIN2A

  6. The Climate of Early Mars

    CERN Document Server

    Wordsworth, Robin

    2016-01-01

    The nature of the early Martian climate is one of the major unanswered questions of planetary science. Key challenges remain, but a new wave of orbital and in situ observations and improvements in climate modeling have led to significant advances over the last decade. Multiple lines of geologic evidence now point to an episodically warm surface during the late Noachian and early Hesperian periods 3-4 Ga. The low solar flux received by Mars in its first billion years and inefficiency of plausible greenhouse gases such as CO2 means that the steady-state early Martian climate was likely cold. A denser CO2 atmosphere would have caused adiabatic cooling of the surface and hence migration of water ice to the higher altitude equatorial and southern regions of the planet. Transient warming caused melting of snow and ice deposits and a temporarily active hydrological cycle, leading to erosion of the valley networks and other fluvial features. Precise details of the warming mechanisms remain unclear, but impacts, volca...

  7. Gastrointestinal causes of abdominal pain.

    Science.gov (United States)

    Marsicano, Elizabeth; Vuong, Giao Michael; Prather, Charlene M

    2014-09-01

    Gastrointestinal causes of abdominal pain are numerous. These causes are reviewed in brief here, divided into 2 categories: acute abdominal pain and chronic abdominal pain. They are further subcategorized by location of pain as it pertains to the abdomen.

  8. Endometriosis: Does It Cause Infertility?

    Science.gov (United States)

    ... Society for Reproductive Medicine Endometriosis: Does It Cause Infertility? This fact sheet was developed in collaboration with ... a surgical procedure called laparoscopy. Does endometriosis cause infertility? If you have endometriosis, it may be more ...

  9. Drugs that may cause impotence

    Science.gov (United States)

    Impotence caused by medications; Drug-induced erectile dysfunction; Prescription medicines and impotence ... Many medicines and recreational drugs can affect a man's sexual arousal and sexual performance. What causes impotence in one ...

  10. Early Lung Cancer Diagnosis by Biosensors

    Directory of Open Access Journals (Sweden)

    Lianhui Wang

    2013-07-01

    Full Text Available Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs, as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted.

  11. [Early detection and treatment of strabismus].

    Science.gov (United States)

    Mojon, Daniel

    2016-01-01

    An early diagnosis of strabismus is important in order to rule out treatable organic causes and in children, if indicated, to start as early as possible with an amblyopia treatment. Early detection will also decrease the risk for accidents secondary to diplopia, to the loss of binocular vision and to the restriction of the binocular visual field in case of esodeviations. The following therapeutic options exist: in some cases the prescription of the correct refraction will be sufficient, for small deviations a prismatic correction may allow a longstanding treatment, for larger or incomitant deviations strabismus surgery will be necessary, which nowadays can be performed using minimal-invasive technique on an outpatient base.

  12. Autism: Why Act Early?

    Science.gov (United States)

    ... What's this? Submit Button Past Emails CDC Features Autism: Why Act Early? Language: English Español (Spanish) Recommend ... helped the world make sense." Florida teenager with Autism Spectrum Disorder "Because my parents acted early, I ...

  13. Overview of Early Intervention

    Science.gov (United States)

    ... infant or toddler for early intervention (e.g., Down syndrome, Fragile X syndrome). Determining eligibility | The results of the evaluation will be used to determine your child’s eligibility for early intervention services. You and a ...

  14. Early Retirement Programs.

    Science.gov (United States)

    Everett, Peter W.

    1984-01-01

    Early retirement programs offer individuals an alternative to the work ethic while allowing them to maintain job security. Examples are given of several early, partial, and phased retirement programs currently being used in universities and public school systems. (DF)

  15. 原发性骨髓纤维化继发门脉高压症六例分析并文献复习%A clinical analysis of six cases of portal hypertension secondary to primary myelofibrosis and review of literatures

    Institute of Scientific and Technical Information of China (English)

    宋志强; 周丽雅

    2010-01-01

    目的 探讨原发性骨髓纤维化(PMF)继发门脉高压症患者的临床特点.方法 对北京大学第三医院确诊的6例PMF继发门脉高压症患者进行临床分析,并进行文献复习.结果 6例患者中,男、女各3例,年龄(52.8±11.7)岁,临床起病至确诊的中位时间为24个月.门脉高压症相关症状主要包括腹胀、腹部包块、呕血和黑便,体征主要包括脾大(均为中重度肿大)、肝大(以轻中度肿大多见)、移动性浊音阳性和腹壁静脉曲张,而黄疸、肝掌和蜘蛛痣少见.大多数患者的肝功能指标正常.门、脾静脉宽度为(16.0±3.2)、(11.0±3.4)mm,2例合并门静脉或脾静脉血栓.1例患者进行了肝穿刺,显示有髓外造血.5例患者接受了门脉高压症相关药物治疗,脾切除术和食管曲张静脉套扎治疗各1例.结论 PMF继发门脉高压症临床罕见,极易误诊.脾大显著、轻中度肝大、肝功能较好、肝掌和蜘蛛痣等体征少见、肝穿刺显示髓外造血等是其与肝硬化的鉴别要点.%Objective To investigate the clinical characteristics of the patients with portal hypertension secondary to primary myelofibrosis (PH-PMF). Methods The clinical data of patients with PH-PMF retrieved from Peking University Third Hospital were collected and analyzed. Results A total of 6 from illness onset to definite diagnosis was 24 months. The symptoms related to portal hypertension included bloating, abdominal mass, hematemesis and melena. The signs related to portal hypertension included splenomegaly ( moderate or severe in all patients), hepatomegaly ( mild or moderate in most of patients),shifting dullness positive and varices in abdominal wall. Only a small portion of patients had jaundice, liver palms and spider angioma. The indexes related to liver functions were normal or only mild abnormal in most cases. The average diameters of portal vein and splenic vein were ( 16. 0 ±3.2) mm and ( 11.0 ±3.4) mm

  16. English language diachronic morphologic change causes new point of view

    Directory of Open Access Journals (Sweden)

    Е В Бондаренко

    2008-09-01

    Full Text Available Any language is a systematic-structural organization. Its inner structure is characterized by having an ability to self-development. The self-organization theory offers new ideas of diachronic language change causes explanation. The English language morphological changes causes of early stages development must be thought of as a combination of inner language abilities to self-development and extra linguistic factors.

  17. 胰蛋白酶原基因缺失突变导致早发型自身免疫性相关的多器官多发囊肿的研究%Trypsinogen gene deletion mutation causes early onset autoimmune related pulmonary bulla, hepatic multiple cysts

    Institute of Scientific and Technical Information of China (English)

    徐志峰; 林寿榕; 刘奇才; 陈瑞庆; 林丽清; 翁少煌; 郜峰; 庄则豪; 陈金通

    2014-01-01

    Objective To identification of cationic trypsinogen(PRSS1) gene deletion mutation in au-toimmune related multiple cysts and its pathogenic mechanism. Methods All exons and flanking intron shear region of pancreatitis and polycystic lesions related genes including PRSS1 , cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1), protein kinase D1(PKD1) and PKD2 were analyzed by DNA sequencing technology. The sequential variation of DNA and cDNA were de-tected. Whether the variation associated with disease were detected by comparing with family inside and healthy controls. The mutant expression system was constructed and its functional verification was done. At the same time, immunohistochemical and special staining in patients with lung and liver pancreas biopsy samples were executed. Results In two patients with autoimmune pancreatitis, deletion mutant in exon 2 of PRSS1 gene were first found, and it generating activation peptide deletion trypsinogen with biological activity. The liv-er, lung was lymphocytic and plasma cell infiltration, elastic fibers and reticular fibers decreased the formation of multiple organ polycystic disease. Serum trypsin, elastase and alpha antitrypsin increased significantly. Use of glucocorticoid treatment was effective. Conclusion PRSS1:c.1300_1304 del CCCAG is a new mutation causes early onset of autoimmune pancreatitis and it correlated with multiple organ cyst closely.%目的:探讨由胰蛋白酶原基因(cationic trypsinogen, PRSS1)突变引发的早发型自身免疫性相关的多器官多发囊肿及其致病机制。方法采用DNA全长测序技术分析PRSS1、囊性纤维化跨膜通道调节因子(cystic fibrosis transmembrane conductance regulator, CFTR)、丝氨酸蛋白酶抑制剂 Kazal 1型(serine protease inhibitor Kazal type 1, SPINK1)、蛋白激酶D(protein kinase D, PKD)1和PKD2等胰腺炎和多囊性病变相关基因的所有外显

  18. Emerging treatment options for myelofibrosis: focus on pacritinib

    OpenAIRE

    Chow V; Weissman A; O’Connell CL; Mehrvar A; Akhtari M

    2016-01-01

    Vivian Chow,1 Ashley Weissman,2 Casey Lee O’Connell,3 Azim Mehrvar,4 Mojtaba Akhtari3 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, 3Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; 4Mahak Children’s Cancer Treatment and Research Center, Tehran, Iran Ab...

  19. Rare causes of closed rupture of the flexor tendon

    NARCIS (Netherlands)

    Stenekes, Martin W.; Ruttermann, Mike; Werker, Paul M. N.

    Closed injuries to the flexor tendon are relatively rare. We present three rare causes of closed injury to the flexor tendon. Early recognition and adequate treatment by a specialised hand surgeon are crucial for the prognosis of such cases. Delayed diagnosis and treatment often require secondary

  20. Rare causes of closed rupture of the flexor tendon

    NARCIS (Netherlands)

    Stenekes, Martin W.; Ruttermann, Mike; Werker, Paul M. N.

    2014-01-01

    Closed injuries to the flexor tendon are relatively rare. We present three rare causes of closed injury to the flexor tendon. Early recognition and adequate treatment by a specialised hand surgeon are crucial for the prognosis of such cases. Delayed diagnosis and treatment often require secondary re

  1. An incorrect diagnosis and an unexpected cause of respiratory failure.

    Science.gov (United States)

    Jandrin, Melanie; Breunig, Michael

    2016-06-01

    Thoracic aortic aneurysms often are asymptomatic or cause nonspecific symptoms such as cough, dyspnea, wheezing, or dysphagia. Acute onset of severe chest, neck, back, or abdominal pain may indicate an aortic rupture or dissection. Early identification and treatment, including optimized medical management and evaluation for surgical intervention, are necessary to improve patient outcomes.

  2. An exceptional cause of left lower quadrant abdominal pain

    Institute of Scientific and Technical Information of China (English)

    Bassam Abboud; Ronald Daher

    2009-01-01

    Acute appendicitis is an exceptional cause of left lower quadrant abdominal pain. Computed tomography scan is the key to its diagnosis and helps to establish its early treatment. We present a case of a 35-year-old male patient who presented acute appendicitis with redundant and loosely attached cecum which was diagnosed based on his left lower quadrant abdominal pain.

  3. Child obesity 1: analysing its prevalence and causes.

    Science.gov (United States)

    Milligan, Fiona

    This is a two-part unit on childhood obesity, which is a major public health concern. With rising levels of the condition it is increasingly obvious that early intervention is key to halting this trend. This first part outlines the prevalence and definition of obesity, and also explores its causes and possible interventions.

  4. Midgut Malrotation Causing Intermittent Intestinal Obstruction in a Young Adult

    OpenAIRE

    Huseyin Kazim Bektasoglu; Ufuk Oguz Idiz; Mustafa Hasbahceci; Erkan Yardimci; Yurdakul Deniz Firat; Oguzhan Karatepe; Mahmut Muslumanoglu

    2014-01-01

    Midgut malrotation is a congenital anomaly of intestinal rotation and fixation that is generally seen in neonatal population. Adult cases are rarely reported. Early diagnosis is crucial to avoid life threatening complications. Here, we present an adulthood case of midgut volvulus as a rare cause of acute abdomen.

  5. Midgut malrotation causing intermittent intestinal obstruction in a young adult.

    Science.gov (United States)

    Bektasoglu, Huseyin Kazim; Idiz, Ufuk Oguz; Hasbahceci, Mustafa; Yardimci, Erkan; Firat, Yurdakul Deniz; Karatepe, Oguzhan; Muslumanoglu, Mahmut

    2014-01-01

    Midgut malrotation is a congenital anomaly of intestinal rotation and fixation that is generally seen in neonatal population. Adult cases are rarely reported. Early diagnosis is crucial to avoid life threatening complications. Here, we present an adulthood case of midgut volvulus as a rare cause of acute abdomen.

  6. The Causes of School Fear

    OpenAIRE

    Hrbáčková, Martina

    2008-01-01

    My bachelor thesis addresses fear of school, especially its causes. It also briefly defines scolinophobia and anxiety related to fear. The causes of school fear are divided into three ranges: child´s personality, family and school environment. The causes of school fear should be sought within the individual himself, but also in the family. I concentrate especially on education of children, which can have the effect of arousing fear. The biggest part on the origin of fear has the school enviro...

  7. Windsurfing hazard caused by needlefish.

    Science.gov (United States)

    Rouvillain, J L; Donica, A; Gane, C; Zekhnini, C; Garron, E; Uzel, A P

    2013-11-01

    Very amusing and entertaining for the traveler, marine activities in tropical countries can be dangerous. More and more trauma caused by hazardous marine animals have been reported in recent years in the world, after maritime accidents including water sports like windsurfing, kite surfing, swimming, diving, and injuries caused by sting or contact with a marine animal. Rays and stone-fish frequently cause trauma, but there are not many cases of injury by needlefish. This case reports a case of penetrating wound of the left foot caused by a Caribbean needlefish occurred during a session of windsurfing in Martinique.

  8. Pompe disease: early diagnosis and early treatment make a difference.

    Science.gov (United States)

    Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lee, Ni-Chung

    2013-08-01

    Pompe disease (glycogen storage disease type II or acid maltase deficiency) is a lysosomal disorder in which acid α-glucosidase (GAA) deficiencies lead to intralysosomal accumulation of glycogen in all tissues; most notably in skeletal muscles. Both the patient's age at the onset of Pompe disease symptoms and the rate of deterioration caused by the disease can vary considerably. In classical infant-onset Pompe disease (IOPD), symptoms start very early in life, and death occurs soon afterward if the disease remains untreated. In later-onset Pompe disease, symptoms are slower to appear, and patients often progress to wheelchair confinement and eventual respiratory failure. A diagnosis can be made by screening for GAA in dried blood samples, followed either by GAA assessment in lymphocytes or in fibroblasts or by the genetic analysis of mutations. Treatment by enzyme replacement therapy (ERT) with alglucosidase alfa was approved for human use in 2006. In classical IOPD, treatment significantly lengthens survival and improves motor development and cardiac function. The sooner ERT begins, the better are the results. Newborn screening aims to take advantage of different technologies for diagnosing and treating newborns early on and it yields better outcomes. However, newborns diagnosed early and other long-term survivors may encounter fresh problems, making up a new phenotype of IOPD patients. Further modifications of the treatment, such as a decrease in immune responses to ERT, a higher dosage, a better uptake formulation, and gene therapy delivered locally or systemically are being explored.

  9. Famines in Africa: is early warning early enough?

    Directory of Open Access Journals (Sweden)

    Jeeyon Janet Kim

    2012-06-01

    Full Text Available Following the second Sahelian famine in 1984–1985, major investments were made to establish Early Warning Systems. These systems help to ensure that timely warnings and vulnerability information are available to decision makers to anticipate and avert food crises. In the recent crisis in the Horn of Africa, alarming levels of acute malnutrition were documented from March 2010, and by August 2010, an impending food crisis was forecast. Despite these measures, the situation remained unrecognised, and further deteriorated causing malnutrition levels to grow in severity and scope. By the time the United Nations officially declared famine on 20 July 2011, and the humanitarian community sluggishly went into response mode, levels of malnutrition and mortality exceeded catastrophic levels. At this time, an estimated 11 million people were in desperate and immediate need for food. With warnings of food crises in the Sahel, South Sudan, and forecast of the drought returning to the Horn, there is an immediate need to institutionalize change in the health response during humanitarian emergencies. Early warning systems are only effective if they trigger an early response.

  10. Pompe Disease: Early Diagnosis and Early Treatment Make a Difference

    Directory of Open Access Journals (Sweden)

    Yin-Hsiu Chien

    2013-08-01

    Full Text Available Pompe disease (glycogen storage disease type II or acid maltase deficiency is a lysosomal disorder in which acid α-glucosidase (GAA deficiencies lead to intralysosomal accumulation of glycogen in all tissues; most notably in skeletal muscles. Both the patient's age at the onset of Pompe disease symptoms and the rate of deterioration caused by the disease can vary considerably. In classical infant-onset Pompe disease (IOPD, symptoms start very early in life, and death occurs soon afterward if the disease remains untreated. In later-onset Pompe disease, symptoms are slower to appear, and patients often progress to wheelchair confinement and eventual respiratory failure. A diagnosis can be made by screening for GAA in dried blood samples, followed either by GAA assessment in lymphocytes or in fibroblasts or by the genetic analysis of mutations. Treatment by enzyme replacement therapy (ERT with alglucosidase alfa was approved for human use in 2006. In classical IOPD, treatment significantly lengthens survival and improves motor development and cardiac function. The sooner ERT begins, the better are the results. Newborn screening aims to take advantage of different technologies for diagnosing and treating newborns early on and it yields better outcomes. However, newborns diagnosed early and other long-term survivors may encounter fresh problems, making up a new phenotype of IOPD patients. Further modifications of the treatment, such as a decrease in immune responses to ERT, a higher dosage, a better uptake formulation, and gene therapy delivered locally or systemically are being explored.

  11. Managing Asthma in the Early Childhood Setting

    Science.gov (United States)

    Graville, Iris

    2011-01-01

    Asthma, one of the most common chronic disorders in childhood, affects more than seven million children in the United States, and is the third leading cause of hospitalization for children. Statistics like these make planning and preparing for asthma in the early childhood setting a high priority. With the high rates of asthma in the U.S. today,…

  12. Causes of banking crises revisited

    NARCIS (Netherlands)

    Klomp, J.G.

    2010-01-01

    We examine to what extent there exists heterogeneity in the causes of a banking crisis. For this purpose, we use a random coefficient logit model including 110 countries between 1970 and 2007. We conclude that there exists significant heterogeneity in the causes of a banking crisis. We find that a h

  13. Optimizing Early Retirement Decisions.

    Science.gov (United States)

    2007-11-02

    the military. The U.S. Army’s early retirement program is a temporary one designed to allow some soldiers to leave the service prior to 20 years of...whether it makes financial sense for an officer to select early retirement . A spreadsheet formulation is developed and used to indicate if and when...an officer should select early retirement . The program investigates the decision that various civilian salary levels and various assumed discount rates.

  14. Deaths: leading causes for 2009.

    Science.gov (United States)

    Heron, Melonie

    2012-10-26

    This report presents final 2009 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2009. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2009, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for approximately 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2009 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  15. Deaths: leading causes for 2010.

    Science.gov (United States)

    Heron, Melonie

    2013-12-20

    This report presents final 2010 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2010. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2010, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Nephritis, nephrotic syndrome and nephrosis; Influenza and pneumonia; and Intentional self-harm (suicide). These 10 causes accounted for 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2010 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and post-neonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source

  16. Deaths: Leading Causes for 2012.

    Science.gov (United States)

    Heron, Melonie

    2015-08-31

    This report presents final 2012 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2012," the National Center for Health Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2012. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2012, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2012 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  17. DIAGNOSTIC OPPORTUNITIES OF NEUROOPHTHALMOLOGIC INSPECTION AT RS: ROLE OF AN OPTICAL COHERENT TOMOGRAPHY AND THE VISUAL CAUSED POTENTIALS IN EARLY DIAGNOSTICS OF MULTIPLE SCLEROSIS AND MONITORING OF A CONDITION OF THE VISUAL ANALYZER AT PATIENTS WITH VARIOUS OPTIONS OF MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Ye. A. Andreyeva

    2013-01-01

    Full Text Available Examination of 70 patients with different options of a course of multiple sclerosis is conducted. Reliable decrease in thickness of a layer of a neuroepithelium and macular volume of a retina at patients with various options of a course of the multiple sclerosis, more expressed is noted at primary progressing and secondary progressing current options, and the patients who have transferred an optical neuritis. The functional violations at the level of an optic nerve according to the visual caused potentials – increase in a latence and decrease in amplitude of the P100 component are revealed. Possibility of application of methods of an optical coherent tomography and the visual caused potentials for diagnostics and monitoring of pathological process is shown at multiple sclerosis.

  18. [Mortality by avoidable causes in preschool children].

    Science.gov (United States)

    Lurán, Albenia; López, Elizabeth; Pinilla, Consuelo; Sierra, Pedro

    2009-03-01

    The infant-mortality rate in children aged less than five is an indicator of the general state of health of a population and directly reflects the quality of life and the level of socio-economic development of a country. Avoidable mortality was assessed in preschool children as a reflection of Colombia quality of life and socio-economic development. Mortality trends were analyzed in preschool children aged less than five throughout Colombia during a 20-year period from 1985-2004, and focused on mortality causes that were considered avoidable. This was a descriptive, retrospective study; the sources of information were Departamento Administrativo Nacional de Estadística records of deaths and population projections 1985-2004. Mortality rate due to avoidable causes was the statistical indicator. In children aged less than one, the reducible mortality due to "early diagnosis and medical treatment" occupied the first place amongst causes for every year of the study period and accounted for more than 50% of recorded deaths. In children aged 1 to 4, the category "other important reducible causes" was associated with 40% of recorded deaths-deaths due mainly to respiratory diseases. Over the 20-year period, the avoidable mortality rate decreased by 34% in children aged less than one, in children 1-4, it decreased by 23%. Although the infant-mortality rate in preschool children was reduced, the decrease was small, from 80% to 77%. The situation requires more analysis with respect to strategies in public health, particularly concerning preventable diseases of the infancy.

  19. Esophageal Foreign Body Causing Direct Aortic Injury

    Directory of Open Access Journals (Sweden)

    ECS Lam

    2003-01-01

    Full Text Available Foreign bodies in the esophagus are uncommon causes of esophageal perforation. Many nonperforating cases are successfully managed by flexible gastroscopy. However, complicated foreign bodies such as those that result in esophageal perforation and vascular injury are best managed surgically. Gastroscopy remains the primary method of diagnosis. A case of a 59-year-old woman who developed retrosternal and intrascapular pain, odynophagia and hematemesis after eating fish is reported. Flexible gastroscopy showed arterial bleeding from the midthoracic esophagus. Computed tomography scan localized a 3 cm fish bone perforating the esophagus with surrounding hematoma. An aortogram did not reveal an actively bleeding aortoesophageal fistula. The fish bone was surgically removed and the patient recovered with no postoperative complications. This case illustrates the importance of early consideration for surgical intervention when confronted with a brisk arterial bleed from the esophagus with suggestive history of foreign body ingestion.

  20. Amoxicillin may cause molar incisor hypomineralization.

    Science.gov (United States)

    Laisi, S; Ess, A; Sahlberg, C; Arvio, P; Lukinmaa, P-L; Alaluusua, S

    2009-02-01

    The etiology of molar incisor hypomineralization (MIH) is unclear. Our hypothesis was that certain antibiotics cause MIH. We examined 141 schoolchildren for MIH and, from their medical files, recorded the use of antibiotics under the age of 4 yrs. MIH was found in 16.3% of children. MIH was more common among those children who had taken, during the first year of life, amoxicillin (OR=2.06; 95% CI, 1.01-4.17) or the rarely prescribed erythromycin (OR=4.14; 95% CI, 1.05-16.4), compared with children who had not received treatment. Mouse E18 teeth were cultured for 10 days with/without amoxicillin at concentrations of 100 microg/mL-4 mg/mL. Amoxicillin increased enamel but not dentin thickness. An altered pattern of amelogenesis may have interfered with mineralization. We conclude that the early use of amoxicillin is among the causative factors of MIH.

  1. Deaths: Leading Causes for 2013.

    Science.gov (United States)

    Heron, Melonie

    2016-02-16

    This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as

  2. Deaths: Leading Causes for 2011.

    Science.gov (United States)

    Heron, Melonie

    2015-07-27

    This report presents final 2011 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements ‘‘Deaths: Final Data for 2011,’’ the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2011. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2011, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2011 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission

  3. What Causes Coronary Microvascular Disease?

    Science.gov (United States)

    ... inside the arteries. Risk factors for atherosclerosis include: Diabetes . It is a disease in which the body’s blood sugar level is too high because the body doesn’t make enough insulin or doesn’t use its insulin properly. Family history of early heart disease . Your risk of atherosclerosis ...

  4. Oxidative stress tolerance of early stage diabetic endothelial progenitor cell

    Directory of Open Access Journals (Sweden)

    Dewi Sukmawati

    2015-06-01

    Conclusions: Primitive BM-EPCs showed vasculogenic dysfunction in early diabetes. However the oxidative stress is not denoted as the major initiating factor of its cause. Our results suggest that primitive BM-KSL cell has the ability to compensate oxidative stress levels in early diabetes by increasing the expression of anti-oxidative enzymes.

  5. Stress in Early Childhood: Helping Children and Their Carers

    Science.gov (United States)

    Thomas, Patrice

    2006-01-01

    This book offers practical and effective strategies for stress management for both early childhood staff and the children in their care. Here, the author uncovers valuable insights into the causes of stress and outlines a range of activities to counteract it. Early childhood practitioners know that theirs is both a stressful and rewarding…

  6. Early College High Schools

    Science.gov (United States)

    Dessoff, Alan

    2011-01-01

    For at-risk students who stand little chance of going to college, or even finishing high school, a growing number of districts have found a solution: Give them an early start in college while they still are in high school. The early college high school (ECHS) movement that began with funding from the Bill and Melinda Gates Foundation 10 years ago…

  7. Early Retirement Payoff

    Science.gov (United States)

    Fitzpatrick, Maria D.; Lovenheim, Michael F.

    2014-01-01

    As public budgets have grown tighter over the past decade, states and school districts have sought ways to control the growth of spending. One increasingly common strategy employed to rein in costs is to offer experienced teachers with high salaries financial incentives to retire early. Although early retirement incentive (ERI) programs have been…

  8. THE FUNDAMENTS OF EXPLANATORY CAUSES

    Directory of Open Access Journals (Sweden)

    Lavinia Mihaela VLĂDILĂ

    2015-07-01

    Full Text Available The new Criminal Code in the specter of the legal life the division of causes removing the criminal feature of the offence in explanatory causes and non-attributable causes. This dichotomy is not without legal and factual fundaments and has been subjected to doctrinaire debates even since the period when the Criminal Code of 1969 was still in force. From our perspective, one of the possible legal fundaments of the explanatory causes results from that the offence committed is based on the protection of a right at least equal with the one prejudiced by the action of aggression, salvation, by the legal obligation imposed or by the victim’s consent.

  9. Other Causes of Leg Pain

    Science.gov (United States)

    ... include: A muscle cramp (also called a charley horse), frequently caused by the following: Dehydration or low ... overstretched muscle (strain) Hairline crack in the bone (stress fracture) Inflamed tendon (tendinitis) Shin splints—pain in ...

  10. Addison's Disease: Symptoms and Causes

    Science.gov (United States)

    ... Low blood sugar (hypoglycemia) Nausea, diarrhea or vomiting Abdominal pain Muscle or joint pains Irritability Depression Body hair loss ... in both men and women. They cause sexual development in men, and influence muscle mass, libido and ...

  11. Chronic Fatigue Syndrome (CFS): Causes

    Science.gov (United States)

    ... patients and in persons with related disorders like fibromyalgia. Cortisol suppresses inflammation and cellular immune activation, and ... 1994 Case Definition Causes Who's at Risk? Symptoms Diagnosis Patient Examination Process Step 1 Step 2 Step ...

  12. Cradle Cap: Symptoms and Causes

    Science.gov (United States)

    Cradle cap Symptoms and causes By Mayo Clinic Staff Common signs of cradle cap include: Patchy scaling or thick crusts on the ... on the ears, eyelids, nose and groin. Cradle cap is common in newborns. It usually isn't ...

  13. Human Caused Fire and Acres

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — Number of wildland fires and acres burned as a result of human causes, from 2001 through 2008 (updated annually). Displayed by the eleven Geographic Areas used by...

  14. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Olesen, Christian Gammelgaard; Nielsen, RG; Rathleff, M;

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist of ...... is in pain but the effect of this treatment has not been documented. Therefore the authors wanted to investigate if it was possible to measure a change in foot posture after af given treatment.......Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...

  15. Does excessive pronation cause pain?

    DEFF Research Database (Denmark)

    Olesen, Christian Gammelgaard; Nielsen, R.G.; Rathleff, M.;

    2008-01-01

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist of ...... pronation patients recieve antipronation training often if the patient is in pain but wanted to investigate if it was possible to measure a change in foot posture after af given treatment.......Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...

  16. Cervicomedullary neurocysticercosis causing obstructive hydrocephalus.

    Science.gov (United States)

    Wang, Doris D; Huang, Michael C

    2015-09-01

    We present a 45-year-old man with tussive headache and blurred vision found to have obstructive hydrocephalus from a neurocysticercal cyst at the cervicomedullary junction who underwent surgical removal of the cyst. We performed a suboccipital craniectomy to remove the cervicomedullary cyst en bloc. Cyst removal successfully treated the patient's headaches without necessitating permanent cerebrospinal fluid diversion. Neurocysticercosis is the most common parasite infection of the central nervous system causing seizures and, less commonly, hydrocephalus. Intraventricular cysts or arachnoiditis usually cause hydrocephalus in neurocysticercosis but craniocervical junction cysts causing obstructive hydrocephalus are rare. Neurocysticercosis at the craniocervical junction may cause Chiari-like symptoms. In the absence of arachnoiditis and leptomeningeal enhancement, surgical removal of the intact cyst can lead to favorable outcomes.

  17. Research Areas: Causes of Cancer

    Science.gov (United States)

    Understanding the exposures and risk factors that cause cancer, as well as the genetic abnormalities associated with the disease, has helped us to reduce certain exposures and to ameliorate their harmful effects.

  18. Nongenetic causes of Parkinson's disease.

    Science.gov (United States)

    Chade, A R; Kasten, M; Tanner, C M

    2006-01-01

    Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.

  19. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  20. Could Anemia Cause Hearing Loss?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162793.html Could Anemia Cause Hearing Loss? Iron deficiency might keep ear ... Hearing loss may be linked to iron deficiency anemia -- a combination of low levels of iron and ...

  1. What Causes High Blood Pressure?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Causes of High Blood Pressure Changes, either from genes or the environment, in ... and blood vessel structure and function. Biology and High Blood Pressure Researchers continue to study how various changes in ...

  2. What Causes Heart Valve Disease?

    Science.gov (United States)

    ... a heart attack or injury to the heart. Rheumatic Fever Untreated strep throat or other infections with strep bacteria that progress to rheumatic fever can cause heart valve disease. When the body ...

  3. Facebook Bullying Can Cause Depression

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160991.html Facebook Bullying Can Cause Depression Social media attacks have ' ... Sept. 15, 2016 (HealthDay News) -- Negative experiences on Facebook can increase the odds of depression in young ...

  4. Infant Reflux: Symptoms and Causes

    Science.gov (United States)

    ... the stomach contents to have enough acid to irritate the throat or esophagus and to cause signs ... as: GERD. The reflux has enough acid to irritate and damage the lining of the esophagus. Pyloric ...

  5. What Causes Thrombocythemia and Thrombocytosis?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes Thrombocythemia and Thrombocytosis? Primary Thrombocythemia In this condition, faulty stem cells ... scarring of the bone marrow can occur. Secondary Thrombocytosis This condition occurs if another disease, condition, or ...

  6. Dementia due to metabolic causes

    Science.gov (United States)

    ... interact Pneumonia , urinary tract infections , and skin infections Pressure sores Symptoms of the underlying problem (such as loss ... in mental status or a life-threatening emergency. Prevention Treating the underlying cause may reduce the risk ...

  7. Science 101: What Causes Wind?

    Science.gov (United States)

    Robertson, William C.

    2010-01-01

    There's a quick and easy answer to this question. The Sun causes wind. Exactly how the Sun causes wind takes a bit to explain. We'll begin with what wind is. You've no doubt heard that wind is the motion of air molecules, which is true. Putting aside the huge leap of faith it takes for us to believe that we are experiencing the motion of millions…

  8. Science 101: What Causes Wind?

    Science.gov (United States)

    Robertson, William C.

    2010-01-01

    There's a quick and easy answer to this question. The Sun causes wind. Exactly how the Sun causes wind takes a bit to explain. We'll begin with what wind is. You've no doubt heard that wind is the motion of air molecules, which is true. Putting aside the huge leap of faith it takes for us to believe that we are experiencing the motion of millions…

  9. Epidemiology and possible causes of autism.

    Science.gov (United States)

    Jick, Hershel; Kaye, James A

    2003-12-01

    To review the recent literature on possible causes of the increase in frequency of diagnosed autism reported from three countries, and to compare the medical diagnoses and drug therapy from a new series of autistic boys and their mothers with that of comparable nonautistic boys and their mothers. Case-control evaluation. Members of over 250 general practices in the United Kingdom. Frequency of exposure to drugs and presence of preexisting clinical illnesses in autistic children and their mothers were compared with nonautistic children and their mothers over time. According to published studies, the incidence of boys diagnosed with autism rose dramatically in the 1990s. Numerous published studies have concluded that the measles-mumps-rubella vaccine is not responsible for the large rise in diagnosed autism. In our study, boys diagnosed with autism had medical and drug histories, such as vaccines, before diagnosis, that were closely similar to those of nonautistic boys, except that developmental and sensory disorders were far more common in autistic boys. No material differences during pregnancy were found between the mothers of autistic boys and those of nonautistic boys in relation to illness or drug therapy. In the early 1990s, boys with diagnosed developmental disorders were infrequently diagnosed with autism. In the later 1990s, such boys more often were diagnosed with autism. A major cause of the recent large increase in the number of boys diagnosed with autism probably is due to changing diagnostic practices.

  10. Acute Pancreatitis Caused By Mushroom Poisoning

    Directory of Open Access Journals (Sweden)

    Samet Karahan Research Fellow

    2016-01-01

    Full Text Available Of the more than 5000 species of mushrooms known, 100 types are toxic and approximately 10% of these toxic types can cause fatal toxicity. A type of mushroom called Amanita phalloides is responsible for 95% of toxic mushroom poisonings. In this article, we report 2 cases of mushroom poisonings caused by Lactarius volemus, known as Tirmit by the local people. The patient and his wife were admitted to the emergency room with abdominal pain, nausea, and vomiting 20 hours after consuming Lactarius volemus, an edible type of mushroom. The patients reported that they had been collecting this mushroom from the mountains and eating them for several years but had never developed any clinicopathology to date. Further examination of the patients revealed a very rare case of acute pancreatitis due to mushroom intoxication. The male patient was admitted to the intensive care unit while his wife was followed in the internal medicine service, because of her relative mild clinical symptoms. Both patients recovered without sequelae and were discharged. In this article, we aimed to emphasize that gastrointestinal symptoms are often observed in mushroom intoxications and can be confused with acute pancreatitis, thus leading to misdiagnosis of patients. Early diagnosis and appropriate treatment can improve patients’ prognosis and prevent the development of complications.

  11. An unusual cause of fungal pneumonia

    Directory of Open Access Journals (Sweden)

    S Dharmic

    2015-01-01

    Full Text Available A 65 year old female, known asthmatic on steroids intermittently, with no other co-morbidity presented with fever, breathlessness and cough with mucoid expectoration of ten days duration with bilateral crepts, went for Type II respiratory failure and was intubated followed by tracheostomy in view of prolonged ventilator support. In spite of high end antibiotics as per sputum culture sensitivity, weaning off the ventilator was not possible. Blood investigations revealed leucocytosis with neutrophilic predominance and I g E levels were within normal limits. CT chest showed multiple patchy consolidations of the right upper, middle and lower lobes with ground glass appearance and enlarged mediastinal lymph nodes. Work up for retrovirus, tuberculosis and Sputum for KOH mount was negative. No evidence of sputum and blood eosinophilia. BAL sample grew Curvularia species. Fluconazole 150mg OD was added. Serial imaging of the chest showed resolution of the consolidation and was weaned off the ventilator and was comfortable on room air. Pneumonia caused by Curvularia, in an immune competent patient is very rare. Even in broncho pulmonary involvement these fungi usually occur in allergic conditions as in ABPA than appearing as a solitary cause for lung infection. But if diagnosed and treated early, will respond well to triazoles. This case report highlights a unilateral fungal pneumonia with dramatic clinical improvement post treatment once the rare causative organism was identified.

  12. Otoneurologic disturbances caused by solvent pollution.

    Science.gov (United States)

    Odkvist, L M; Möller, C; Thuomas, K A

    1992-06-01

    Subjects exposed to industrial solvents may experience vertigo and nausea. Solvents are usually volatile hydrocarbon compounds, which are important parts of everyday life in a modern society. They may also cause neurastenia, personality changes, and reduced intellectual capacity. The syndrome that may develop was formerly named psycho-organic syndrome (POS), but in modern terminology it is called chronic toxic encephalopathy (CTE). The syndrome develops slowly, and during the first years no pathological findings will be found using various test batteries. Somewhat later, when the syndrome still might be reversible, psychometric, auditory, and otoneurologic testing may well unveil disturbances within the posterior fossa structures. Animal experiments suggest one site of effect for solvents to be within the cerebellum and brainstem regions with close relationship to the gamma-amino-butyric acid (GABA) transmission. In the otoneurologic test battery, visual suppression and smooth pursuit are of extreme value, as are some auditory tests such as discrimination of interrupted speech and cortical response audiometry using frequency glides as stimuli. Dynamic posturography and magnetic resonance imaging (MRI) have recently proved valuable in the diagnosis. Research is needed concerning the most efficient test battery for early detection of solvent-induced lesions. During further research it is important to unveil other toxic agents, like heavy metals and alcohol, and their damage to the central nervous system and to make comparisons between these substances and the lesions caused by hydrocarbon solvents.

  13. Suitable time of treating maxillofacial trauma caused by traffic accident in general hospitals

    Institute of Scientific and Technical Information of China (English)

    桑修文; 赵宏伟; 等

    1999-01-01

    Objective To explore sutitable time of treating maxillofacial trauma caused by traffic accident in general hospitals to decrease adverse effect caused by delayed therapy.Methods:In recent 10 years we have treated 154 cases of maxillofacial trauma by traffic accidents and their data were analyzed.Results:Early surgical therapy could be done in maxillofacial soft tissue trauma.The therapy of returning occlusion relation or temporary fixing was performed in bone fracture before porosis.Conclusions:For maxilloficial trauman and trauman of other parts caused by traffic accidents.early treatment should be done in order to decrease dysfunction and deformity caused by maxillofacial trauma.

  14. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Lockwood, Charles J;

    2010-01-01

    The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy...... cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non...... cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes....

  15. Metabolic Causes of Epileptic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Joe Yuezhou Yu

    2013-01-01

    Full Text Available Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies. Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category.

  16. Early Option Exercise

    DEFF Research Database (Denmark)

    Heje Pedersen, Lasse; Jensen, Mads Vestergaard

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  17. Early Option Exercise

    DEFF Research Database (Denmark)

    Jensen, Mads Vestergaard; Heje Pedersen, Lasse

    2016-01-01

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  18. Uncommon Causes of Cerebral Microbleeds.

    Science.gov (United States)

    Noorbakhsh-Sabet, Nariman; Pulakanti, Varun Chandi; Zand, Ramin

    2017-10-01

    Cerebral microbleeds (CMBs) are small and round perivascular hemosiderin depositions detectable by gradient echo sequences or susceptibility-weighted imaging. Cerebral microbleeds are common among patients with hypertension, cerebral ischemia, or cerebral amyloid angiopathy. In this article, we describe uncommon causes of CMBs. We searched Pubmed with the keyword CMBs for relevant studies and looked for different uncommon causes of CMBs. CMBs have several uncommon etiologies including posterior reversible encephalopathy syndrome, infective endocarditis, brain radiation therapy, cocaine abuse, thrombotic thrombocytopenic purpura, traumatic brain injury, intravascular lymphomatosis or proliferating angio-endotheliomatosis, moyamoya disease, sickle cell anemia/β-thalassemia, cerebral autosomal dominant arteriopathy subcortical infarcts, and leukoencephalopathy (CADASIL), genetic syndromes, or obstructive sleep apnea. Understanding the uncommon causes of CMBs is not only helpful in diagnosis and prognosis of some of these rare diseases, but can also help in better understanding different pathophysiology involved in the development of CMBs. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Mølgaard, Carsten Møller; Olesen Gammelgaard, Christian; Nielsen, R. G.;

    2008-01-01

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...... of antipronation shoes or insoles, which latest was studied by Kulce DG., et al (2007). So far there have been no randomized controlled studies showing methods that the effect of this treatment has not been documented. Therefore the authors can measure the effect of treatments with insoles. Some of the excessive...

  20. Occupational asthma caused by ethanolamines.

    Science.gov (United States)

    Savonius, B; Keskinen, H; Tuppurainen, M; Kanerva, L

    1994-12-01

    Amino alcohols are used in various industries, often as minor constituents of compounds to modify the properties of the compound. Generally, they are considered to be safe, but they have been known to cause local skin irritation at higher concentrations in solutions. We report on three cases of occupational asthma caused by ethanolamines: two metal workers exposed to a cutting fluid containing triethanolamine, and one cleaner exposed to a detergent containing monoethanolamine. The diagnosis was based on work-related symptoms and on a chamber challenge with the suspected agent. Persistence of the symptoms after exposure ended was a common feature of the three cases.