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Sample records for causing severe neutropenia

  1. Severe congenital neutropenia

    DEFF Research Database (Denmark)

    Borregaard, Niels

    2014-01-01

    In this issue of Blood, Tidwell et al1 demonstrate that mutations in the start codon (protein synthesis is initiated at the codon ATG) of neutrophil elastase (ELANE) result in the production of N-terminally truncated elastase, which mislocates to the nucleus and results in severe congenital neutr...... neutropenia (SCN)....

  2. Severe congenital neutropenia (Kostmann Syndrome)

    African Journals Online (AJOL)

    Severe congenital neutropenia (SCN), Kostmann syndrome is a heterogenous disorder of myelopoiesis characterized by severe chronic ... erogenous hematological disorders, characterized by extremely low circu- lating neutrophils and ..... tic activation of STAT5 and stimulate. G-CSF-induced cell proliferation.26, 27.

  3. Genetics Home Reference: severe congenital neutropenia

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... Genetic Testing Registry: Severe congenital neutropenia 2, autosomal dominant Genetic Testing Registry: Severe congenital neutropenia 3, autosomal ...

  4. Different Clinical Phenotypes in Familial Severe Congenital Neutropenia Cases with Same Mutation of the ELANE Gene

    OpenAIRE

    Cho, Hye-Kyung; Jeon, In Sang

    2014-01-01

    Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profou...

  5. Severe neutropenia revealing a rare presentation of dengue fever: a case report.

    Science.gov (United States)

    Shourick, J; Dinh, A; Matt, M; Salomon, J; Davido, B

    2017-08-17

    Arboviruses are a common cause of fever in the returned traveler often associated with leucopenia, especially lymphopenia and thrombocytopenia. Transient neutropenia has been described in a few cases of arboviruses. However, prolonged and severe neutropenia (dengue fever, especially in the returned traveler in Europe. A 26-year-old healthy female without any medical past history, flying back from Thailand, presented a transient fever with severe neutropenia (dengue fever. Outcome was favorable without any antimicrobial therapy. Physicians should be wary of possible unusual presentation of dengue fever with prolonged neutropenia. Although such biological sign is more often associated with malaria or severe bacterial infection, it may be a sign of arbovirus.

  6. Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene.

    Science.gov (United States)

    Cho, Hye-Kyung; Jeon, In Sang

    2014-03-01

    Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profound neutropenia, and her mother, a 32-yr-old woman (patient 3), had had recurrent stomatitis until her early 20s with neutropenia. We found an ELANE gene mutation (c.597+1G > A) from them in direct DNA sequencing analysis. Patients 1 and 2 did not respond to granulocyte colony stimulating factor and patient 1 was treated with prolonged antibiotics and excision. We demonstrated inherited SCN cases showing different severity even with the same mutation of the ELANE gene in a family.

  7. Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

    OpenAIRE

    Okolo, Onyemaechi N.; Katsanis, Emmanuel; Yun, Seongseok; Reveles, Candace Y.; Anwer, Faiz

    2017-01-01

    Objective and Importance. Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk o...

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

    Directory of Open Access Journals (Sweden)

    Weihan Chen BS

    2017-03-01

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

  9. Game of clones: the genomic evolution of severe congenital neutropenia.

    Science.gov (United States)

    Touw, Ivo P

    2015-01-01

    Severe congenital neutropenia (SCN) is a genetically heterogeneous condition of bone marrow failure usually diagnosed in early childhood and characterized by a chronic and severe shortage of neutrophils. It is now well-established that mutations in HAX1 and ELANE (and more rarely in other genes) are the genetic cause of SCN. In contrast, it has remained unclear how these mutations affect neutrophil development. Innovative models based on induced pluripotent stem cell technology are being explored to address this issue. These days, most SCN patients receive life-long treatment with granulocyte colony-stimulating factor (G-CSF, CSF3). CSF3 therapy has greatly improved the life expectancy of SCN patients, but also unveiled a high frequency of progression toward myelodysplastic syndrome (MDS) and therapy refractory acute myeloid leukemia (AML). Expansion of hematopoietic clones with acquired mutations in the gene encoding the G-CSF receptor (CSF3R) is regularly seen in SCN patients and AML usually descends from one of these CSF3R mutant clones. These findings raised the questions how CSF3R mutations affect CSF3 responses of myeloid progenitors, how they contribute to the pre-leukemic state of SCN, and which additional events are responsible for progression to leukemia. The vast (sub)clonal heterogeneity of AML and the presence of AML-associated mutations in normally aged hematopoietic clones make it often difficult to determine which mutations are responsible for the leukemic process. Leukemia predisposition syndromes such as SCN are unique disease models to identify the sequential acquisition of these mutations and to interrogate how they contribute to clonal selection and leukemic evolution. © 2015 by The American Society of Hematology. All rights reserved.

  10. Severe neutropenia in children: a single institutional experience.

    Science.gov (United States)

    Yilmaz, Deniz; Ritchey, Arthur Kim

    2007-08-01

    Severe neutropenia (SN) is a rare disorder in childhood. This study aimed to document the approach to diagnosis and treatment of children with SN in a single university-based children's hospital, determine the types of SN seen in a 4-year period, and determine outcomes of the subtypes of SN. Forty-five children with SN were identified between 2000 and 2004. Two patients had autoimmune, 3 congenital, 3 familial, 6 cyclic, and 31 idiopathic SN. The median age of the patients with idiopathic SN was 15 months (3 mo to 17 y). Thirteen patients with idiopathic SN received filgrastim and 18 were observed. The history of severe infection and hospitalization at presentation was significantly more common among the patients who received filgrastim than those observed, but was not different between the 2 groups during the follow-up period. SN resolved in 16 patients and persisted in 14 patients. One patient with idiopathic SN did not respond to filgrastim and died of sepsis while she was still neutropenic. In summary, the majority of patients with SN had idiopathic SN, the infection risk was variable, treatment was based on clinical judgment rather than absolute neutrophil count, and approximately half of the patients had complete recovery.

  11. Inherited biallelic CSF3R mutations in severe congenital neutropenia.

    Science.gov (United States)

    Triot, Alexa; Järvinen, Päivi M; Arostegui, Juan I; Murugan, Dhaarini; Kohistani, Naschla; Dapena Díaz, José Luis; Racek, Tomas; Puchałka, Jacek; Gertz, E Michael; Schäffer, Alejandro A; Kotlarz, Daniel; Pfeifer, Dietmar; Díaz de Heredia Rubio, Cristina; Ozdemir, Mehmet Akif; Patiroglu, Turkan; Karakukcu, Musa; Sánchez de Toledo Codina, José; Yagüe, Jordi; Touw, Ivo P; Unal, Ekrem; Klein, Christoph

    2014-06-12

    Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. © 2014 by The American Society of Hematology.

  12. Indomethacin-associated neutropenia with subsequent Gram-negative sepsis in a preterm infant. Cause or coincidence?

    Science.gov (United States)

    Bengtsson, B-O S; Milstein, J M; Sherman, M P

    2006-06-01

    A preterm male infant with a patent ductus arteriosus developed neutropenia during treatment with indomethacin. Afterward, the mother described her own history of indomethacin-associated neutropenia. During the recovery from the neutropenia, the infant became septic with bacteremia caused by Enterobacter cloacae. Although indomethacin-related neutropenia has been described in adults, no case in a neonate has been reported. If neutropenia occurs after indomethacin therapy in a neonate, a familial history of indomethacin-associated neutropenia should be sought and the increased risk of infection should be considered.

  13. Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

    Directory of Open Access Journals (Sweden)

    Onyemaechi N. Okolo

    2017-01-01

    Full Text Available Objective and Importance. Cyclic neutropenia (CyN is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection. Case. A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV mutation. Intervention. Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation positive severe CyN. Conclusion. BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV may have contributed to the severity of this individual’s symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.

  14. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

    Science.gov (United States)

    Wortmann, Saskia B; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B; Gersting, Søren W; Muntau, Ania C; Rakovic, Aleksandar; Renkema, G Herma; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Rubio-Gozalbo, M Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N; Vaz, Frédéric M; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A A P; de Brouwer, Arjan P M; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A

    2015-02-05

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome.

    Science.gov (United States)

    Guffroy, Aurélien; Mourot-Cottet, Rachel; Gérard, Laurence; Gies, Vincent; Lagresle, Chantal; Pouliet, Aurore; Nitschké, Patrick; Hanein, Sylvain; Bienvenu, Boris; Chanet, Valérie; Donadieu, Jean; Gardembas, Martine; Karmochkine, Marina; Nove-Josserand, Raphaele; Martin, Thierry; Poindron, Vincent; Soulas-Sprauel, Pauline; Rieux-Laucat, Fréderic; Fieschi, Claire; Oksenhendler, Eric; André-Schmutz, Isabelle; Korganow, Anne-Sophie

    2017-10-01

    Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*10 6 /L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21 low CD38 low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

  16. Familial severe congenital neutropenia associated with infantile osteoporosis: a new entity.

    Science.gov (United States)

    Elhasid, R; Hofbauer, L C; Ish-Shalom, S; Ben-Arush, M; Koc, O; Rowe, J M; Etzioni, A

    2003-01-01

    A new entity manifested by severe congenital neutropenia associated with osteoporosis and recurrent bone fracture is described in a family. A possible role for a new recognized cytokine system involved in bone remodeling, the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand, is suggested. Copyright 2002 Wiley-Liss, Inc.

  17. Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Sven Geissler

    Full Text Available Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN. Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF or late (SPF+nonSPF pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

  18. Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia.

    Science.gov (United States)

    Setty, Bhuvana A; Yeager, Nicholas D; Bajwa, Rajinder P

    2011-09-01

    Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia Copyright © 2011 Wiley-Liss, Inc.

  19. The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

    Science.gov (United States)

    Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

    2003-03-01

    Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

  20. Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Taaning, Ellen; Jensen, Lise; Varming, Kim

    2012-01-01

    Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

  1. Severe neutropenia at time of port insertion is not a risk factor for catheter-associated infections in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Junqueira, Beatriz L P; Connolly, Bairbre; Abla, Oussama; Tomlinson, George; Amaral, Joao G

    2010-09-15

    The objective of this study was to determine whether severe neutropenia on the day of port-a-catheter (PORT) insertion was a risk factor for catheter-associated infection (CAI) in children with acute lymphoblastic leukemia (ALL). This was a retrospective study of children with ALL who had a PORT insertion between January 2005 and August 2008. Early (≤ 30 days) and late (>30 days) postprocedure complications were reviewed. The length of follow-up ranged between 7 months and 42 months. In total, 192 PORTs were inserted in 179 children. There were 43 CAIs (22%), and the infection rate was 0.35 per 1000 catheter-days. The CAI rate (15%) in children who had severe neutropenia on the day of the procedure did not differ statistically from the CAI rate (24%) in children who did not have severe neutropenia (P = .137). Conversely, patients with severe neutropenia who had a CAI were more likely to have their PORT removed (P = .019). The most common organisms to cause catheter removal were coagulase-negative Staphylococcus and Staphylococcus aureus. Patients with high-risk ALL had a statistically significant higher incidence of late CAI than patients with standard-risk ALL (P = .012). Age (P = .272), positive blood culture preprocedure (P = 1.0), and dexamethasone use (P = .201) were not risk factors for CAI. Patients who had an early CAI did not have a greater chance of having a late CAI. The catheter infection-free survival rate at 1 year was 88.6%. The current results indicated that severe neutropenia on the day of PORT insertion does not increase the risk of CAI in children with ALL. © 2010 American Cancer Society.

  2. Predictors of Outcome and Severity in Adult Filipino Patients with Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    Marc Gregory Y. Yu

    2015-01-01

    Full Text Available Aim. The study aimed to describe the profile of Filipino febrile neutropenia patients and to determine parameters associated with severe outcomes. Methods. This is a retrospective study of Filipino febrile neutropenia patients admitted to the Philippine General Hospital. Patients were described in terms of clinical presentation and stratified according to the presence or absence of severe outcomes. Prognostic factors were then identified using regression analysis. Results. 115 febrile episodes in 102 patients were identified. Regression analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI, 0.77–7.74, isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04–6.98, and nadir absolute neutrophil count (ANC 7 days prior to admission, positive pathogen on cultures, and nadir ANC < 100 during admission predicted severe outcomes, whereas G-CSF use and complete antibiotic therapy were associated with better outcomes. These prognostic variables might be useful in identifying patients that need more intensive treatment and monitoring.

  3. Four novel ELANE mutations in patients with congenital neutropenia.

    Science.gov (United States)

    Kurnikova, Maria; Maschan, Michael; Dinova, Evgeniya; Shagina, Irina; Finogenova, Natalia; Mamedova, Elena; Polovtseva, Tatyana; Shagin, Dmitry; Shcherbina, Anna

    2011-08-01

    Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations. Copyright © 2011 Wiley-Liss, Inc.

  4. How I manage children with neutropenia.

    Science.gov (United States)

    Dale, David C

    2017-08-01

    Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 9 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia. © 2017 John Wiley & Sons Ltd.

  5. Emergence of MRSA in positive blood cultures from patients with febrile neutropenia--a cause for concern.

    LENUS (Irish Health Repository)

    Morris, Patrick G

    2008-09-01

    Febrile neutropenia (FN) causes considerable morbidity in patients on cytotoxic chemotherapy. Recently, there has been a trend towards fewer Gram-negative and more Gram-positive infections with increasing antibiotic resistance. To assess these patterns, data from a supra-regional cancer centre in Ireland were reviewed.

  6. Relato de um caso de neutropenia congênita grave em um lactente jovem A case report of severe congenital neutropenia in a young infant

    Directory of Open Access Journals (Sweden)

    Lucas Fadel M. dos Santos

    2011-12-01

    Full Text Available OBJETIVO: Relatar um caso de neutropenia congênita grave e alertar os pediatras sobre tal diagnóstico em pacientes jovens, com infecções recorrentes. DESCRIÇÃO DO CASO: Lactente jovem com 45 dias de vida, com história de febre alta, letargia, recusa alimentar e hemogramas repetidos com leucopenia importante à custa de polimorfonucleares. A hipótese diagnóstica foi confirmada pelo aspirado de medula óssea, que mostrou hipoplasia de série granulocítica e completa ausência de neutrófilos maduros. Foi introduzida antibioticoterapia de largo espectro e estimulador da formação de colônias de granulócitos. O paciente evoluiu para óbito em decorrência de complicações infecciosas após 21 dias de internação. COMENTÁRIOS: Trata-se de um lactente jovem, portador de uma rara desordem congênita que leva à intensa neutropenia, deixando-o vulnerável a infecções graves e potencialmente fatais. À internação, o paciente apresentava sinais e sintomas sugestivos de sepse, sendo introduzido antibioticoterapia de amplo espectro, necessária por se tratar de lactente jovem, neutropênico e febril. A hipótese diagnóstica se baseou na história clínica e nos leucogramas alterados, sendo posteriormente confirmada pelo aspirado de medula óssea. Foi introduzido o estimulador da formação de colônias de granulócitos, que geralmente é efetivo, porém, nesse caso, não houve sucesso e o paciente evoluiu para óbito devido à grave infecção.OBJECTIVE: To report a case of severe congenital neutropenia and alert pediatricians about its diagnosis in young patients with recurrent infectious diseases. CASE DESCRIPTION: Young infant with 45 days of life, with a history of high fever, lethargy, poor feeding and repeated blood counts showing significant leucopenia due to a significant decrease of polymorphonuclear cells. The diagnosis was confirmed by bone marrow aspirate showing hypoplasia of the granulocytic series and complete absence of

  7. Relationship between ELA2 gene mutations, clinical and laboratory parameters in severe congenital and cyclic neutropenia

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    Farhoodi A

    2007-09-01

    Full Text Available   Background: Mutations of ELA2, the gene encoding neutrophil elastase (NE are known to be associated with cyclic neutropenia (CN and severe congenital neutropenia (SCN. However, high variability of these mutations has been reported. This study was designed to describe the analysis of the ELA2 gene, clinical manifestations and demographic characteristics in patients with CN and SCN.Methods: A series of 21 patients with CN or SCN were selected, based on SCINR criteria, from the immunology ward of the Pediatric Medicine Center, Tehran, Iran, from March 2004 to August 2005. The ELA2 gene, isolated from blood samples, was analyzed using RT-PCR and automated capillary sequencing. Informed consent was obtained under the tenets of the Helsinki Declaration and the Ethical Committee of the Tehran University of Medical Sciences.Results: Kostmann's syndrome and CN was diagnosed in three and 18 patients respectively. Of all the patients, one or two mutations were found in 18 cases (85.7%, including all three patients with SCN and 15 of the patients with CN. Exons two and four had the most mutations (eight and seven cases, respectively. Seven patients had double mutations in two distinct exons. Overall, 16 different mutations were found. At the time of presentation, the mean age of patients was 13.4 ±17.6 months, ranging from one month to seven years. Overall, 61.9% of patients had consanguineous parents. The mean absolute neutrophil count was 830.5 ±419.4 (150-2000/mm3. On average, each patient had been admitted to the hospital 2.2 ±1.6 times. The neutrophil counts of the SCN patients were significantly higher than those of the CN patients. However, there was no significant difference in the neutrophil counts between patients with mutations and those without mutations. All patients with SCN had two or more infectious complications, although the prevalence of infectious or non-infectious complications did not correlate with ELA2 mutations or the

  8. Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.

    Science.gov (United States)

    Malcov, Mira; Reches, Adi; Ben-Yosef, Dalit; Cohen, Tania; Amit, Ami; Dgany, Orly; Tamary, Hannah; Yaron, Yuval

    2010-03-01

    Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice-site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child. A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing. The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm-cell populations: (1) sperm cells harboring the ELA2 mutation on the 'affected' haplotype, (2) sperm cells without the ELA2 mutation on the 'normal' haplotype, and (3) sperm cells without the ELA2 mutation on the 'affected' haplotype. These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ-line mosaicism. This conclusion was also taken into consideration when PGD was performed. Copyright (c) 2010 John Wiley & Sons, Ltd.

  9. Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4 phenotype

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    Fernandez Bridget A

    2012-11-01

    Full Text Available Abstract Background Severe congenital neutropenia type 4 (SCN4 is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3. Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4 is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.

  10. PROCALCITONIN AND INTERLEUKIN-6 AS MARKERS OF SEVERE INFECTION IN CHILDREN WITH FEBRILE NEUTROPENIA

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    Lidija Kitanovski

    2004-12-01

    Full Text Available Background. The results of the study conducted to determine whether procalcitonin (PCT and interleukin-6 (IL-6 are more sensitive and specific markers of severe infection in children with febrile neutropenia (FN than routinelly used C-reactive protein (CRP are presented in the article. 68 episodes of FN experienced by 32 patients were divided into three groups according to the site of infection. Group 1: episodes of bacteraemia and/or clinical sepsis (n = 16, group 2: episodes of focal infection (n = 16 and group 3: episodes of fever of unknown origin (FUO (n = 36. Blood samples for further PCT and IL-6 determination were collected on three consecutive days. CRP concentrations were measured daily in each patient until the resolution of fever. PCT, IL-6 and CRP concentrations were measured on one occassion in each of the 18 afebrile patients with malignant disase forming the reference group. Serum PCT and IL-6 concentrations were measured by immunochemiluminometric and immunoenzymatic assay. Receiver Operating Characteristic (ROC curves were used to determine optimum sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of the studied parameters.Conclusions. PCT and IL-6 were found to be earlier and more sensitive markers of severe infection in neutropenic patients than CRP. The erliest one was IL-6, followed by PCT and CRP. Sequential determination of PCT up to 72 hours improved its diagnostic value, which was not the case for IL-6.In patients with gramnegative bacteraemias PCT concentracions were 3–5 times higher comparing to grampositive, whereas IL-6 concentrations were comparable in both groups.

  11. Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Hwang, Jun-Eul; Yoon, Ju-Young; Bae, Woo-Kyun; Shim, Hyun-Jeong; Cho, Sang-Hee; Chung, Ik-Joo

    2010-01-01

    Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST. A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities. The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug

  12. Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

    Science.gov (United States)

    Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

    2017-01-01

    Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

  13. Neutropenia in the Newborn

    Science.gov (United States)

    Maheshwari, Akhil

    2013-01-01

    PURPOSE OF REVIEW Review normal blood neutrophil concentrations and the clinical approach to neutropenia in the neonatal period. A literature search on neonatal neutropenia was performed using the databases PubMed, EMBASE, and Scopus and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RECENT FINDINGS This review summarizes current knowledge on the causes of neutropenia in premature and critically-ill neonates, focusing on common causes such as maternal hypertension, neonatal sepsis, twin-twin transfusion, alloimmunization, and hemolytic disease. The article provides a rational approach to diagnosis and treatment of neonatal neutropenia, including current evidence on the role of recombinant hematopoietic growth factors. SUMMARY Neutrophil counts should be carefully evaluated in premature and critically-ill neonates. Although neutropenia is usually benign and runs a self-limited course in most neonates, it can be prolonged and constitute a serious deficiency in antimicrobial defense in some infants. PMID:24322487

  14. Serum endocan levels in children with febrile neutropenia

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    Eylem Kiral

    2016-03-01

    Full Text Available Endocan is an endotelial cell specific molecule; previous studies have shown that serum endocan levels increased in cancer and sepsis and are also related to the severity of sepsis. There are no clinical study about serum endocan levels in children with febrile neutropenia. The aim of this study was to evaluate serum endocan levels in pediatric leukemia patients with febrile neutropenia (n=33 and compare them with children with leukemia without fever (n=33 and also with healthy children (n=24. The median serum endocan level in the first group (children with febrile neutropenia was statistically significantly higher compared to the leukemic children without febrile neutropenia and also control group (P<0.01 for both. No difference was determined between the serum endocan levels of the leukaemia patients without febrile neutropenia and the healthy control group (P>0.05. Serum endocan levels were also similar with febrile neutropenia due to bacterial causes comparing with the idiopathic febril neutropenia. The results of this study showed increased serum endocan in children with leukemia during the febrile neutropenia episode, and no changes of serum endocan levels in children without leukemia without infection/fever. The monitoring of a series of serum endocan levels would be helpful for the course of febrile neutropenia.

  15. Severe Neutropenia at the Time of Implantable Subcutaneous Chest Port Insertion Is Not a Risk Factor for Port Removal at a Tertiary Pediatric Center.

    Science.gov (United States)

    Hoss, Daniel R; Bedros, Antranik A; Mesipam, Avinash; Criddle, Jared; Smith, Jason C

    2017-03-01

    To determine if severe neutropenia at the time of chest port insertion is a risk factor for port removal and central catheter-associated bloodstream infection (CCABSI) in pediatric patients. From May 2007 to June 2015, 183 consecutive patients (mean age, 9.9 y; range, 0.75-21 y) had a port inserted at a single tertiary pediatric center. Seventy-two had severe neutropenia at the time of port insertion (absolute neutrophil count [ANC] range, 0-500/mm 3 ; mean, 185/mm 3 ). Follow-up until port removal or death and CCABSI events were recorded. Within the first 30 days, similar incidences of CCABSI (12.5% of patients with severe neutropenia [n = 9] vs 4.5% of patients without [n = 5]), port removal for infection (2.8% [n = 2] vs 2.7% [n = 3]), and local port infection (2.8% [n = 2] vs 0.9% [n = 1]) were observed in both groups (P > .05), but the rate of CCABSI per 1,000 catheter-days was higher for patients with severe neutropenia (P = .045). Overall, similar incidences of CCABSI (18.1% [n = 13] vs 16.2% [n = 18]), port removal for infection (2.8% [n = 2] vs 7.2% [n = 8]), local port infection (2.8% [n = 2] vs 2.7% [n = 3]), and CCABSIs per 1,000 catheter-days (0.332 vs 0.400) were observed in both groups (P > .05). Port placement in patients with severe neutropenia can be performed without an increased incidence of port removal for infection. The majority of CCABSIs were successfully treated without port removal. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  16. La neutropenia severa febril en niños con cáncer: Estudio descriptivo en el Hospital Universitario de Santander Severe febrile neutropenia in children with cancer: A descriptive study at the Hospital Universitario de Santander

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    Ernesto Rueda

    2010-08-01

    Full Text Available Objetivos: Describir una población oncológica afectada por neutropenia severa febril, sus características demográficas, nutricionales, microbiológicas, de tratamiento y severidad de la enfermedad. Materiales y métodos: Esta es una serie de casos prospectiva de los pacientes atendidos en el Hospital Universitario de Santander entre enero/2007 y enero/2008. Resultados: Veintiun (21 pacientes aportaron 35 episodios de neutropenia febril; 65,7% eran hombres, la edad promedio 5,6 años; 38,3% vivían en el Área Metropolitana de Bucaramanga y 91,4% en estrato socioeconómico bajo. El diagnóstico oncológico más frecuente fue leucemia linfocítica aguda. Ninguno presentó dolor abdominal o síntomas neurológicos. La neutropenia se detectó 8,5 días en promedio posterior a la última quimioterapia. El 31,4% no tuvieron neutrófilos absolutos, 54,2% plaquetas Objective: To describe an oncological population affected with severe febrile neutropenia, its demographic, nutritional, and microbiological features, their treatment and severity of the illness. Materials and methods: A descriptive-prospective clinical chart review from attended patients at the Hospital Universitario de Santander, from January/2007 to January/2008. Results: Twenty (21 patients contributed with 35 febrile neutropenia episodes; 65.7% were male; they aged average was 5.6-years; 38.37% lived in Bucaramanga Metropolitan Area; 91.4% had low economic status. The most frequent oncological diagnosis was acute lumphocytic leukemia. No one presented abdominal pain or neurological symptoms. The neutropenia was detected 8.5 days after the last chemotherapy cycle. 31.4% patients had no absolute neutrophils; 54.2% blood platelets <50,000/mm3, 45.7% had reactive C protein <90 mg|/dL. The bloodculture was positive only in 7 patients. It was found the infection focus in 88.6% of the episodes and the most frequently diagnosis were related with the gastrointestinal tract. The most used

  17. Hepatopulmonary syndrome causing severe hypoxaemia

    DEFF Research Database (Denmark)

    Lyngsøe, Bente Kjær; Andersen, Mette Winther; Eriksen, Jan

    2014-01-01

    Dyspnoea is a common complaint in patients with chronic liver disease. Hepatopulmonary syndrome (HPS) is an important cause to be aware of in the setting of liver disease, dyspnoea and hypoxaemia. HPS causes microvascular dilatation, angiogenesis and arteriovenous bypassing. The patients suffer f...... from hypoxaemia in upright position and even during minimal psychical activity. Contrast echocardiography, using micro-bubbles as the contrast, is required to establish the diagnosis. No medical therapy is available, only liver transplantation can cure the disease....

  18. Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

    Science.gov (United States)

    Klepfish, A; Rachmilevitch, E; Schattner, A

    2006-11-01

    A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

  19. Febrile neutropenia in haematological malignancies

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    Sharma A

    2005-01-01

    Full Text Available Fever is the principle sign of infection in neutropenic patient and frequently may be the only evidence of infection. The pattern of fever in neutropenia is non-specific and not pathognomonic of any type of infections or non-infectious process and can be suppressed by the antipyretic effects of drugs such as corticosteroids. Neutropenia, resulting from cytotoxic chemotherapy is the most common risk factor for severe infections in hematological malignancies. The duration of neutropenia also contributes significantly to the risk of serious infections. This risk is significantly greater a lower neutrophil counts, such that 100% patients with ANC < 100 cells/µl lasting 3 weeks or more develop documented infections. The prompt initiation of empirical antibiotics in febrile neutropenia has been the most important advance in the management of the immunocompromised host. The initial empirical antibiotic regimen started at presentation of the febrile episode frequently requires modifications especially in high-risk febrile neutropenia. Neutropenic patients who remain febrile despite 4-7 days of broad spectrum antibacterial therapy are at a high risk of invasive fungal infection. Empirical antifungal therapy with Amphotericin B in persistently febrile neutropenic patients and other high risk patients has shown to reduce the risk of invasive fungal infection by 50-80% and the risk of fungal infection related mortality by 23-45% in 1980′s. The IDSA has recommended that amphotericin B at 0.5-0.7 mg/kg/day be administered till marrow recovery. This approach is limited however by the adverse effects caused by drug infusion (fever, chills, myalgias, nausea, hypotension and bronchospasm. Lipid formulations which improve the therapeutic ratio of the traditional formulation are available. The safety and efficacy of these formulations is well established. These formulations have comparable efficacy and are less nephrotoxic than conventional amphotericin B

  20. Water Extract of Deer Bones Activates Macrophages and Alleviates Neutropenia

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    Han-Seok Choi

    2013-01-01

    Full Text Available Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO synthesis and secretions of cytokines including IL-6 and TNF-α. Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, IκBα, and NF-κB in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia.

  1. Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia

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    Deniz Yilmaz Karapinar

    2015-09-01

    Full Text Available Empirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11–19 days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture. Because the patients’ clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3–7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.

  2. Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer

    OpenAIRE

    Burton, J.H.; Stanley, S.D.; Knych, H.K.; Rodriguez, C.O.; Skorupski, K.A.; Rebhun, R.B.

    2015-01-01

    Background Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)?approved products. Hypothesis/Objectives The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA?approved formulations of lomustine. Subsequent analyses aimed t...

  3. Thickened cortical bones in congenital neutropenia

    International Nuclear Information System (INIS)

    Boechat, M.I.; Gormley, L.S.; O'Laughlin, B.J.

    1987-01-01

    Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described. (orig.)

  4. Thickened cortical bones in congenital neutropenia

    Energy Technology Data Exchange (ETDEWEB)

    Boechat, M.I.; Gormley, L.S.; O' Laughlin, B.J.

    1987-02-01

    Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described.

  5. Neutropenia in pediatric hematology/oncology practice

    Directory of Open Access Journals (Sweden)

    E. A. Deordieva

    2015-06-01

    Full Text Available Acquired neutropenia is one of the most common conditions in pediatric hematology practice. These conditions usually are benign. In contrast, congenital neutropenia are rare conditions, but in the absence of pathogenic therapy can cause fatal complications. Approach to the differential diagnosis and management of these patients are discussed in this review.

  6. Drug induced neutropenia manifesting as oral ulcerations

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    Rachna Kaul

    2009-01-01

    Full Text Available As dental practitioners, we often come across oral ulcerations of varied etiology. Among all the causes of oral ulcers, those due to neutropenia are significant. Neutropenia can occur in many systemic conditions and also in patients on long-term therapy of certain drugs like phenytoin. The diagnosis of neutropenia in time leads to early recognition of the cause of this fatal condition. Here, we report a case of a 50-year-old female patient who developed oral ulcerations secondary to phenytoin-induced neutropenia. Early diagnosis of the condition led to discontinuation of the offending drug and significant improvement in her blood picture and also prevented her from falling prey to many other systemic infections that neutropenia can cause.

  7. An Unexpected Cause of Severe Hypokalemia

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    Fernando Caravaca-Fontan

    2015-01-01

    Full Text Available We describe an unusual case of severe hypokalemia with electrocardiographic changes, due to licorice consumption, in a 15-year-old female student with no previous medical history. Prompt replacement of potassium and cessation of licorice ingestion resulted in a favourable outcome. We also discuss the pathophysiology and diagnosis, emphasizing the importance of a detailed anamnesis to rule out an often forgotten cause of hypokalemia as the licorice poisoning.

  8. Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

    Science.gov (United States)

    Esbenshade, Adam J; Zhao, Zhiguo; Aftandilian, Catherine; Saab, Raya; Wattier, Rachel L; Beauchemin, Melissa; Miller, Tamara P; Wilkes, Jennifer J; Kelly, Michael J; Fernbach, Alison; Jeng, Michael; Schwartz, Cindy L; Dvorak, Christopher C; Shyr, Yu; Moons, Karl G M; Sulis, Maria-Luisa; Friedman, Debra L

    2017-10-01

    Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. Results of high-risk neutropenia therapy of hematology-oncology patients in a university hospital in Uruguay

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    Matilde Boada Burutaran

    2015-02-01

    Full Text Available Background: Febrile neutropenia is an important cause of mortality and morbidity in hematology-oncology patients undergoing chemotherapy. The management of febrile neutropenia is typically algorithm-driven. The aim of this study was to assess the results of a standardized protocol for the treatment of febrile neutropenia. Methods: A retrospective cohort study (2011-2012 was conducted of patients with high-risk neutropenia in a hematology-oncology service. Results: Forty-four episodes of 17 patients with a median age of 48 years (range: 18-78 years were included. The incidence of febrile neutropenia was 61.4%. The presence of febrile neutropenia was associated with both the duration and severity of neutropenia. Microbiological agents were isolated from different sources in 59.3% of the episodes with bacteremia iso- lated from blood being the most prevalent (81.3%. Multiple drug-resistant gram-negative bacilli were isolated in 62.5% of all microbiologically documented infections. Treatment of 63% of the episodes in which the initial treatment was piperacillin/tazobactam needed to be escalated to meropenem. The mortality rate due to febrile neutropenia episodes was 18.5%. Conclusion: The high rate of gram-negative bacilli resistant to piperacillin/tazobactam (frontline antibiotics in our protocol and the early need to escalate to carbapenems raises the question as to whether it is necessary to change the current protocol.

  10. Gastric antral vascular ectasia causing severe anemia.

    Science.gov (United States)

    Toyota, M; Hinoda, Y; Nakagawa, N; Arimura, Y; Tokuchi, S; Takaoka, A; Kitagawa, S; Usuki, T; Yabana, T; Yachi, A; Imai, K

    1996-10-01

    Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal bleeding is reported in a 76-year-old woman who had been treated with repeated blood transfusions because of severe anemia. Endoscopic examination was performed and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory data showed SGOT > SGPT, decreased chE level and the increased levels of serum gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination revealed splenomegaly. There was no family history of telangiectasia, and no telangiectasia was found in other organs. The diagnosis was established as GAVE with liver cirrhosis. Surgical resection of the distal stomach resulted in termination of the bleeding, and the cirrhotic changes of the surface of the liver were revealed at that time, providing further evidence of liver cirrhosis. Although the pathogenesis of GAVE is unknown, liver cirrhosis and hypergastrinemia are thought to be associated with the condition. Importantly, this condition is a cause of severe gastrointestinal bleeding in elderly patients.

  11. Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia.

    Science.gov (United States)

    Freire, M P; de Oliveira Garcia, D; Garcia, C P; Campagnari Bueno, M F; Camargo, C H; Kono Magri, A S G; Francisco, G R; Reghini, R; Vieira, M F; Ibrahim, K Y; Rossi, F; Hajjar, L; Levin, A S; Hoff, P M; Pierrotti, L C; Abdala, E

    2016-04-01

    This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Neutropenia in infants with hemolytic disease of the newborn.

    Science.gov (United States)

    Blanco, Esther; Johnston, Donna L

    2012-06-01

    This study examined the incidence, outcome and risk factors of neutropenia in infants with hemolytic disease of the newborn (HDN). A retrospective chart review was performed on infants with HDN. Of 69 evaluable infants, 45% developed neutropenia. Only one infectious complication was recorded. In most instances the neutropenia resolved spontaneously, but in seven infants it persisted for a median of 397 days. Males were at higher risk for developing neutropenia, but severity of HDN, antibody specificity, or therapy were not significant risk factors. Neutropenia is a common feature of HDN, regardless of severity of disease, treatment received, or antibody specificity. Copyright © 2011 Wiley Periodicals, Inc.

  13. PPIB mutations cause severe osteogenesis imperfecta.

    Science.gov (United States)

    van Dijk, Fleur S; Nesbitt, Isabel M; Zwikstra, Eline H; Nikkels, Peter G J; Piersma, Sander R; Fratantoni, Silvina A; Jimenez, Connie R; Huizer, Margriet; Morsman, Alice C; Cobben, Jan M; van Roij, Mirjam H H; Elting, Mariet W; Verbeke, Jonathan I M L; Wijnaendts, Liliane C D; Shaw, Nick J; Högler, Wolfgang; McKeown, Carole; Sistermans, Erik A; Dalton, Ann; Meijers-Heijboer, Hanne; Pals, Gerard

    2009-10-01

    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I.

  14. Treatment of febrile neutropenia with cefepime monotherapy.

    Science.gov (United States)

    Jándula, B M; Martino, R; Gurgi, M; Manteiga, R; Sierra, J

    2001-01-01

    The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be

  15. Neutropenia, agranulocytosis and dipyrone

    Directory of Open Access Journals (Sweden)

    Nelson Hamerschlak

    Full Text Available CONTEXT: Neutropenia and agranulocytosis may be defined as granulocyte counts of less than 1,500/mm³ and 500/mm³, respectively. Agranulocytosis is a rare and serious disease often caused by drugs. Its mortality rate is around 10%. The most common manifestations are infections such as tonsillitis, pharyngitis, stomatitis or pneumonia. Although dipyrone is one of the drugs known to be associated with agranulocytosis, the strength of the association has been a matter of much debate. Moreover, alternative analgesic and antipyretic agents are not devoid of serious side effects. CONCLUSIONS: It is therefore necessary to establish the incidence of agranulocytosis in Latin America and the role of dipyrone. The ongoing LATIN Study is a multicenter international case-control study that will provide answers for these questions.

  16. PPIB mutations cause severe osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Nesbitt, Isabel M.; Zwikstra, Eline H.; Nikkels, Peter G. J.; Piersma, Sander R.; Fratantoni, Silvina A.; Jimenez, Connie R.; Huizer, Margriet; Morsman, Alice C.; Cobben, Jan M.; van Roij, Mirjam H. H.; Elting, Mariet W.; Verbeke, Jonathan I. M. L.; Wijnaendts, Liliane C. D.; Shaw, Nick J.; Högler, Wolfgang; McKeown, Carole; Sistermans, Erik A.; Dalton, Ann; Meijers-Heijboer, Hanne; Pals, Gerard

    2009-01-01

    Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position

  17. Febrile neutropenia and refeeding syndrome.

    Science.gov (United States)

    Jahn, H K; Barraclough, S; Currell, S; Tighe, M P

    2016-12-01

    We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Congenital neutropenia: diagnosis, molecular bases and patient management

    Directory of Open Access Journals (Sweden)

    Chantelot Christine

    2011-05-01

    Full Text Available Abstract The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe ( When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency and glycogen storage disease type Ib (associated with a glycogen storage syndrome. So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF. G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.

  19. The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies

    DEFF Research Database (Denmark)

    Ye, Ying; Carlsson, Göran; Karlsson-Sjöberg, Jenny M T

    2015-01-01

    The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels...... in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic...... diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low...

  20. {sup 18}F-FDG PET/CT for diagnosing infectious complications in patients with severe neutropenia after intensive chemotherapy for haematological malignancy or stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Vos, Fidel J.; Kullberg, Bart-Jan; Bleeker-Rovers, Chantal P. [Radboud University Nijmegen Medical Centre, Department of Internal Medicine, PO Box 9101, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Donnelly, J.P.; Blijlevens, Nicole M.A. [Radboud University Nijmegen Medical Centre, Department of Hematology, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-01-15

    Between 30 and 50% of febrile neutropenic episodes are accounted for by infection. C-reactive protein (CRP) is a nonspecific parameter for infection and inflammation but might be employed as a trigger for diagnosis. The aim of the study was to evaluate whether {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT can be used to detect inflammatory foci in neutropenic patients with elevated CRP and whether it helps to direct treatment. Twenty-eight consecutive patients with neutropenia as a result of intensive chemotherapy for haematological malignancies or myeloablative therapy for haematopoietic stem cell transplantation were prospectively included. {sup 18}F-FDG PET/CT was added to the regular diagnostic workup once the CRP level rose above 50 mg/l. Pathological FDG uptake was found in 26 of 28 cases despite peripheral neutrophil counts less than 0.1 x 10{sup -9}/l in 26 patients: in the digestive tract in 18 cases, around the tract of the central venous catheter (CVC) in 9 and in the lungs in 7 cases. FDG uptake in the CVC tract was associated with coagulase-negative staphylococcal bacteraemia (p < 0.001) and deep venous thrombosis (p = 0.002). The number of patients having Streptococcus mitis bacteraemia appeared to be higher in patients with grade 3 oesophageal FDG uptake (p = 0.08). Pulmonary FDG uptake was associated with the presence of invasive fungal disease (p = 0.04). {sup 18}F-FDG PET/CT scanning during chemotherapy-induced febrile neutropenia and increased CRP is able to detect localized foci of infection and inflammation despite the absence of circulating neutrophils. Besides its potential role in detecting CVC-related infection during febrile neutropenia, the high negative predictive value of {sup 18}F-FDG PET/CT is important for avoiding unnecessary diagnostic tests and therapy. (orig.)

  1. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.

    Science.gov (United States)

    Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C

    2001-11-01

    Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

  2. Triagem para o tratamento ambulatorial da neutropenia febril Screening for the outpatient treatment of febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Marcelo Bellesso

    2010-01-01

    Full Text Available A neutropenia febril (NF é uma complicação frequente e potencialmente fatal nos pacientes em tratamento quimioterápico. Entendemos hoje que a neutropenia febril é considerada uma emergência clínica e que a administração de antibióticos de amplo espectro diminui drasticamente a mortalidade. Estudos sugerem que a neutropenia febril compreende um grupo extremamente heterogêneo e que dados clínicos como febre domiciliar, ausência de hipotensão, ausência de desidratação, ausência de doença pulmonar obstrutiva crônica, ausência de outros sintomas, ausência de infecção fúngica prévia e idade Febrile neutropenia is a frequent and potentially fatal adverse event of chemotherapy. Nowadays, febrile neutropenia is considered an emergency and it is known that prompt infusion of antibiotics decreases mortality. Several studies demonstrated that febrile neutropenia is a heterogeneous group of diseases and that factors such as outpatient status, no hypotension, no dehydration, no chronic obstructive pulmonary disease, no symptoms, no previous fungal infection and age < 60 years are protective factors against serious complications as demonstrated by the Multinational Association for Supportive Care in Cancer (MASCC. These data show that outpatient treatment and early discharge is safer and much research has shown lower costs for outpatient treatment in low-risk patients with febrile neutropenia. The aim of this work is to review and discuss tools (in particular the MASCC index for safe screening of febrile neutropenia for outpatient treatment in addition to demonstrate results of research.

  3. Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

    Directory of Open Access Journals (Sweden)

    Rui-Rui Peng

    2017-03-01

    Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

  4. Science 101: What Causes Severe Thunderstorms and Tornadoes?

    Science.gov (United States)

    Robertson, Bill

    2016-01-01

    What causes severe thunderstorms and tornadoes? Tornadoes, often accompanied by severe thunderstorms and hail, form in pretty much the same way as severe thunderstorms. In the continental United States, tornadoes usually form in spring and summer, when warm, humid air from the Gulf of Mexico moves across the continent from southeast to northwest…

  5. Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Tesfa, D.; Siersma, Volkert Dirk

    2016-01-01

    BACKGROUND: Neutropenia, defined as an absolute blood neutrophil count (ANC) neutropenia detected in a routine complete blood cell count is poorly understood. METHODS: Using a primary care resource, comprising...... more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed....... RESULTS: Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias...

  6. Effects of Traditional Chinese Medicine on Chemotherapy-Induced Myelosuppression and Febrile Neutropenia in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Huan Tian

    2015-01-01

    Full Text Available Title. Chemotherapy-induced myelosuppression lowers the quality of life in breast cancer patients and causes many complications. Traditional Chinese Medicine (TCM is a widely used complementary and alternative medicine therapies. Objective. To study whether TCM can reduce the incidence of chemotherapy-induced leukopenia, neutropenia, and febrile neutropenia (FN in breast cancer patients. Methods. The data were analyzed retrospectively between patients who received TCM treatment (group 1, n=453 and patients who did not receive TCM treatment (group 2, n=359. Significant risk factors associated with the occurrence of chemotherapy-induced leukopenia, neutropenia, and FN were identified using multivariate analysis. Propensity score-matched patients were analyzed to adjust for any baseline differences. Results. Group 1 patients had a significantly lower rate of chemotherapy-induced severe leukopenia, neutropenia, and FN, compared with group 2 (43% versus 71%, P<0.0001, 72% versus 78%, P=0.005, 6% versus 24%, P<0.0001, resp.. Multivariate analysis revealed that chemotherapy regimens containing anthracyclines combined with paclitaxel or docetaxel were the most significant predictor. Subgroup analysis indicated that TCM treatment showed benefit in relieving chemotherapy-induced leukopenia and FN in most chemotherapy regimens. Conclusions. TCM treatment could lower the risk of severe chemotherapy-induced leukopenia, neutropenia, and FN in breast cancer patients.

  7. Intermittent chronic neutropenia in a patient with familial Mediterranean fever.

    Science.gov (United States)

    Ganiou Tidjani, K; Ailal, F; Najib, J; Bellanné-Chantelot, C; Donadieu, J; Bousfiha, A A

    2008-11-01

    A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia. (c) 2008 Wiley-Liss, Inc.

  8. Treatment of severe mitral regurgitation caused by lesions in both ...

    African Journals Online (AJOL)

    Mitral valve plasty (MVP) is preferred over mitral valve replacement (MVR) for mitral regurgitation in humans because of its favorable effect on quality of life. In small dogs, it is difficult to repair multiple lesions in both leaflets using MVP. Herein, we report a case of severe mitral regurgitation caused by multiple severe lesions ...

  9. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    Directory of Open Access Journals (Sweden)

    Emmanuel Gyan

    2015-02-01

    Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

  10. [Causes and management of severe acute liver damage during pregnancy].

    Science.gov (United States)

    Sepulveda-Martinez, Alvaro; Romero, Carlos; Juarez, Guido; Hasbun, Jorge; Parra-Cordero, Mauro

    2015-05-01

    Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

  11. Systematic review of severe acute liver injury caused by terbinafine.

    Science.gov (United States)

    Yan, Jun; Wang, Xiaolin; Chen, Shengli

    2014-08-01

    Terbinafine is an effective antimicrobial agent against dermatophytes, cryptococcus and other fungi. It is the preferred drug to treat onychomycosis. However, severe acute hepatitis from oral terbinafine administration has been recently reported. To describe a representative case, and review the literature regarding the best evidence on treatment and prognosis of severe acute hepatitis caused by oral terbinafine. The literature was searched for publications on severe hepatitis caused by terbinafine using MEDLINE, China Biology Medicine Disc, and the VIP Medical Information Resource System. Related references were searched manually. Seventeen English and three Chinese references of case reports were included after eliminating duplicate publications. No randomized control studies were found. Liver enzyme levels were found to have been increased significantly. Abdominal ultrasound demonstrated cholestasis. Severe acute liver injury is a known, but unusual complication of terbinafine exposure. The prognosis is often good with appropriate treatment. Liver function assessment before treatment and periodic monitoring 4-6 weeks after initiation of treatment is recommended.

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

    Science.gov (United States)

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

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

  13. Febrile neutropenia in childhood cancer

    African Journals Online (AJOL)

    To classify and treat patients with febrile neutropenia adequately, one has to have a ... 48 hours.2,4,5. Approach. A child with possible febrile neutropenia should be viewed as a ... treating centre for information on the child's treatment if the family do not have a ... treatment, such as antimicrobial therapy, as well as the nature.

  14. [Rare cause for severe hypertriglyceridemia - case 9/2013].

    Science.gov (United States)

    Kahl, Sabine; Roden, Michael; Mörike, Klaus; Müssig, Karsten

    2013-11-01

    We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Technetium-99m DMSA preparation: Trivial issues causing severe problems

    International Nuclear Information System (INIS)

    Kumar, V.

    1997-01-01

    Urinary tract infection (UTI) in children involving renal parenchyma, upper collecting system or bladder is one of the major causes for consideration in the diagnosis and management of paediatric nuclear medicine. Acute pyelonephritis is one of the prime causes of morbidity associated with urinary tract infection in children which can lead to progressive renal damage. Technetium-99m dimercaptosuccinic acid (DMSA) is used extensively for the assessment of UTI in paediatrics. The radiopharmaceutical preparation could be influenced by several factors, most of them are trivial, but invariably have severe impact on the quality of the scintiphotographs. This communication is mainly to highlight some of the issues related to 99 mTc-DMSA preparation and the possible precautionary measures that need to be taken to obviate unwarranted problems. (author)

  16. [Severe Eyeball and Facial Skeletal Injuries Caused by Firefighting Sport].

    Science.gov (United States)

    Rusňák, Š; Maranová, Z; Kasl, Z; Hecová, L; Voigt, E; Raiskup, F

    2017-07-01

    The aim of this work is to draw attention to possible injuries of the eye and the facial skeleton caused by firefighting sport. There was a group of 9 patients presented who were treated from 2006 to 2015 in the Department of Ophthalmology at the University Hospital in Pilsen and diagnosed with severe eyeball contusion after being hit by a jet of water and/or a water pipe. Three cases are presented in detail. Georg Thieme Verlag KG Stuttgart · New York.

  17. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    OpenAIRE

    Emmanuel Gyan; François Dreyfus; Pierre Fenaux

    2015-01-01

    Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medi...

  18. Leukopenia and neutropenia caused by sertraline%舍曲林致白细胞和中性粒细胞减少

    Institute of Scientific and Technical Information of China (English)

    庄红艳; 刘珊珊; 杜海霞; 崔永华

    2016-01-01

    1例11岁女性患儿因童年情绪障碍服用舍曲林25 mg、喹硫平25 mg,1次/ d。2 d 后实验室检查:WBC 4.6×109/ L,中性粒细胞计数(NEUT)1.8×109/ L。诊断:中性粒细胞减少。停用喹硫平,继续服用舍曲林,给予盐酸小檗胺84 mg、利可君20 mg,3次/ d 口服。6 d 后为改善病情,舍曲林剂量增至50 mg,1次/ d。同时加用维生素 B610 mg,3次/ d 口服。舍曲林治疗第13天,患儿 WBC 3.5×109/ L ,NEUT 1.4×109/ L,诊断为白细胞减少。舍曲林治疗第24天,患儿 WBC 3.3×109/ L, NEUT 1.4×109/ L。加用安多霖胶囊0.64 g,2次/ d 口服。次日舍曲林减量至25 mg,1次/ d,2 d 后停用。5 d 后复查,患儿 WBC 4.4×109/ L,NEUT 2.0×109/ L。给予氟伏沙明改善情绪。7 d 后,患儿WBC 4.6×109/ L,NEUT 2.3×109/ L。%An 11-year-old female patient was given sertraline 25 mg once daily and quetiapine 25 mg once daily for childhood emotional disorders. The patient's white blood cells count(WBC)was 4. 6 ×109 / L and neutrophil count( NEUT)was 1. 8 ×109 / L two days later. The patient was diagnosed as neutropenia. Quetiapine was stopped and sertraline was given continually. At the same time berbamine hydrochloride 84 mg thrice daily and leucogen 20 mg thrice daily were given. Six days later,the dosage of sertraline was increased to 50 mg once daily to improve the symptoms and vitamin B6 10 mg thrice daily was given. On day 13 of sertraline therapy,the WBC was 3. 5 ×109 / L and the NEUT was 1.4×109 / L. Leukopenia was diagnosed. On day 24 of sertraline therapy,the WBC was 3. 3 ×109 / L and the NEUT was 1.4×109 / L. Anduolin(安多霖)capsules 0. 64 g twice daily were added to her regimen. Sertraline dose was reduced to 25 mg once daily the next day and was stopped 2 days later. Five days later,the patient's WBC was 4.4×109 / L and NEUT was 2. 0 ×109 / L. Then,fluvoxamine was given to improve mood. Seven days later,the patient's WBC was 4. 6

  19. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  20. Immune-Mediated Neutropenia and Thrombocytopenia in a Patient with Ulcerative Colitis: An Unusual Hematological Association with IBD

    Directory of Open Access Journals (Sweden)

    Young-In Kim

    1995-01-01

    Full Text Available Hematological manifestations of inflammatory bowel disease (IBD are well described in the literature. However, the combination of immune-mediated neutropenia and thrombocytopenia has only been reported once in association with IBD. A case is reported of immune-mediated neutropenia and thrombocytopenia in a patient with ulcerative colitis during a relapse. No obvious causes of these hematological abnormalities were found in the patient despite an exhaustive search. An immune-mediated process was confirmed by positive antineutrophil antibody and platelet-associated antibody in the patient’s serum, and the demonstration of binding of the patient’s immunoglobulin G to autologous neutrophils. The patient was treated with high-dose steroid, intravenous gamma-globulin and eventually splenectomy. The platelet count subsequently normalized; although the severe neutropenia recurred, it has subsequently improved without further treatment. Although a definitive cause-effect relationship cannot be established, the immune-mediated neutropenia and thrombocytopenia may be an unusual hematological manifestation associated with ulcerative colitis.

  1. Surgical correction of severe enophthalmos caused by bullet injury

    Directory of Open Access Journals (Sweden)

    S M Balaji

    2016-01-01

    Full Text Available Ballistic injuries of oral and maxillofacial region are usually fatal due to close propinquity with the vital structures. The severity of injury depends on the caliber of the weapon used and distance from which the patient is shot. The preliminary care of facial ballistic wounds strictly adheres to the basics of trauma resuscitation. Early and appropriate surgical management has proved to be influential on the final outcome and esthetic result. Treatment of facial gunshot wounds should be planned and carried out carefully to avoid esthetic complications. It takes even multiple-staged corrections to achieve the targeted functional and esthetic treatment plan. Prevention and control of infection is one of the most important goals to achieve the success of the treatment. Herewith, we present a case of facial gunshot injury with fractures in the orbital floor, medial wall maxillary sinus, and buttress of the zygomatic bone causing deficit, which was successfully managed by surgical reconstruction.

  2. [Asthma and cyclic neutropenia].

    Science.gov (United States)

    Salazar Cabrera, A N; Berrón Pérez, R; Ortega Martell, J A; Onuma Takane, E

    1996-01-01

    We report a male with history of recurrent infections (recurrent oral aphtous disease [ROAD], middle ear infections and pharyngo amigdalitis) every 3 weeks since he was 7 months old. At the age of 3 years cyclic neutropenia was diagnosed with cyclic fall in the total neutrophil count in blood smear every 21 days and prophylactic antimicrobial therapy was indicated. Episodic events every 3 weeks of acute asthma and allergic rhinitis were detected at the age of 6 years old and specific immunotherapy to Bermuda grass was given during 3 years with markedly improvement in his allergic condition but not in the ROAD. He came back until the age of 16 with episodic acute asthma and ROAD. The total neutrophil count failed to 0 every 21 days and surprisingly the total eosinophil count increased up to 2,000 at the same time, with elevation of serum IgE (412 Ul/mL). Specific immunotherapy to D.pt. and Aller.a. and therapy with timomodulin was indicated. After 3 months we observed clinical improvement in the asthmatic condition and the ROAD disappeared, but the total neutrophil count did not improve. We present this case as a rare association between 2 diseases with probably no etiological relationship but may be physiopatological that could help to understand more the pathogenesis of asthma.

  3. Severe Hand Injuries Caused by a Mole Gun

    Directory of Open Access Journals (Sweden)

    Serdar Düzgün

    2017-10-01

    Full Text Available Objective: Injuries by mole guns differ from other firearm injuries primarily because they are close-range, low-energy injuries that are highly contaminated owing to contact with contaminated surfaces and the presence of numerous residual foreign bodies within the wound. The aim of this article is to share our surgical experience regarding the repair of severe hand injuries caused by mole guns. Material and Methods: This retrospective study included 11 patients with hand injuries. Data obtained about the patients, including age, gender, dominant or non-dominant hand, injuries to all vital structures, and reconstructive procedures were assessed, categorized, and recorded. Results: Ten patients had defects in one or several common digital branches of the median nerve in areas ranging from the distal part of the carpal tunnel to the distal palmar crease. All patients had flexor and extensor tendon injuries in all fingers except for the first finger. Reconstruction of soft tissue and skin defects was carried out with an interpolation flap planned from a random-based subpectoral- paraumbilical region in five patients, a SCIA-based groin flap in four patients, a reverse-radial forearm flap in one patient, and an adipofascial flap planned from the forearm in one patient. Conclusion: Mole gun injuries typically include all structures of the hand, and repair procedures involve every anatomic structure of the hand. An early and effective surgical operation followed by prolonged and effective physical therapy protocols is vital for regaining the full spectrum of hand functions.

  4. How we diagnose and treat neutropenia in adults.

    Science.gov (United States)

    Palmblad, Jan; Nilsson, Christer C; Höglund, Petter; Papadaki, Helen A

    2016-05-01

    Neutropenias (NPs), being acute and often transient, or chronic, range from life-threatening conditions with very low absolute neutrophil blood counts (ANC) to disorders characterized by only mild NP and of no obvious significance for health. Many are caused by genetic variations/mutations, e.g. the benign familial NP and the chronic severe NPs (e.g. Kostmann disease). Some of the latter are associated with various bodily malformations. Many of the mild-to-moderate NPs are signs of underlying disorders that need specialized treatments (e.g. HIV, hepatitis, autoimmune disorders, the large granular lymphocyte syndrome). We provide here means for the evaluation of a previously unknown NP, suggest a triage and treatments.

  5. Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

    Science.gov (United States)

    Richardson, Danielle; Poirier, Valerie J; Matsuyama, Arata; Calvalido, Jerome

    Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m 2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P 10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P 15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

  6. Family caring strategies in neutropenia.

    Science.gov (United States)

    Eggenberger, Sandra K; Krumwiede, Norma; Meiers, Sonja J; Bliesmer, Mary; Earle, Patricia

    2004-12-01

    Aggressive chemotherapy protocols result in neutropenia in approximately half of all patients receiving chemotherapy. Thus, neutropenia continues to be a significant and potentially life-threatening side effect of treatment, even with use of colony-stimulating factors. Families of patients with neutropenia often provide the primary healing environment because most chemotherapy protocols are managed on an outpatient basis. To learn about the family's experience of managing chemotherapy-induced neutropenia (CIN), a grounded-theory methodology was used to analyze data from seven families. The central theme revealed by these families was "turbulent waiting with intensified connections." This meant that when families had a sense of greater vulnerability in response to the waiting after diagnosis of CIN, they connected intensely with each other and healthcare providers. Families reported that connections with nurses became more significant when neutropenia interrupted chemotherapy. Families also developed family caring strategies to manage this period of waiting for the chemotherapy to resume. These strategies included family inquiry, family vigilance, and family balancing. Nurses need to be aware of approaches to support the family's ability to manage CIN. Interventions and approaches constructed from the perspective of a family-professional partnership will enhance the family cancer experience as well as ongoing family growth and function.

  7. Microbiology of destructive periodontal disease in adolescent patients with congenital neutropenia - A report of 3 cases

    NARCIS (Netherlands)

    van Winkelhoff, AJ; Schouten-van Meeteren, AYN; Baart, JA; Vandenbroucke-Grauls, CMJE

    Background, aims: Congenital neutropenia is one condition that may predispose for destructive periodontal disease at a young age. In this report, we describe the microbiology of 3 adolescent patients with congenital neutropenia two of whom suffered from severe periodontitis. Method: Microbiological

  8. Evaluasi Sensitivitas Antibiotik dengan Demam Neutropenia

    Directory of Open Access Journals (Sweden)

    Sulaiman Hamid

    2016-11-01

    Kesimpulan. Bakteri Gram negatif merupakan penyebab utama demam neutropenia. Sensitivitas cefotaxime lebih rendah apabila dibandingkan dengan antibiotik yang lain. Cefpirome, cefepime dan ampicillin-sulbactam direkomendasikan untuk menggantikan cefotaxime sebagai obat yang dikombinasikan dengan gentamicin pada pengobatan demam neutropenia.

  9. Accelerate Genomic Aging in Congenital Neutropenia

    Science.gov (United States)

    2017-10-01

    reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...neutropenia; Shwachman Diamond syndrome; Cyclic neutropenia; Hematopoietic stem cells; Granulocyte colony- stimulating factor; Acute myeloid leukemia...high rate of leukemic transformation. For example, granulocyte colony stimulating factor (G-CSF) expression is induced by neutropenia and may increase

  10. Kejadian Demam Neutropenia pada Anak dengan Keganasan

    Directory of Open Access Journals (Sweden)

    Sarah Rafika Nursyirwan

    2018-03-01

    Kesimpulan. kejadian demam neutropenia lebih sering terjadi pada pasien dengan keganasan darah. Patogen ditemukan pada sebagian pasien dengan demam neutropenia. Penyebab terbanyak bakteremia adalah bakteri Gram positif. Sensitivitas antibiotik tertinggi didapatkan pada vankomisin. Data mengenai pola sensitivitas antibiotik terbaru diperlukan untuk pedoman tata laksana pasien demam neutropenia.

  11. [Severe hypertriglyceridemia--an important cause of pancreatitis].

    Science.gov (United States)

    Graesdal, Asgeir

    2008-05-01

    Moderate hypertriglyceridaemia is a risk factor for cardiovascular disease and serious hypertriglyceridaemia, with triglyceride values above 10 mmol/L, increases the risk of pancreatitis. Gallstones and alcohol abuse are regarded as the two most important causes of acute pancreatitis, but the considerable risk posed by hypertriglyceridaemia has probably been underrated. It is therefore crucial to acquire updated knowledge and awareness of the fact that high levels of triglycerides can cause pancreatitis. This article is based on current literature retrieved though a search on the topic and clinical experience. Serious hypertriglyceridaemia is a relatively rare condition and its usual cause is genetic predisposition combined with obesity, diabetes or alcohol abuse. Certain types of medication, as well as pregnancy, are also well known causes. Current literature suggests that hypertriglyceridaemia is the cause of pancreatitis in 1-38% of the cases--a substantial variation. The condition is often accompanied by low amylase values and may therefore be underrated as a cause. Our case reports illustrate that the etiology is complex. Plasmapheresis or LDL-apheresis may be indicated when conservative treatment proves insufficient.

  12. Periodontal disease in three siblings with familial neutropenia.

    Science.gov (United States)

    Kirstilä, V; Sewón, L; Laine, J

    1993-06-01

    The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described. The mother was also diagnosed with neutropenia. At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease. The two siblings with periodontitis were treated and followed approximately 5 years. It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction. The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

  13. Cochlear implantation for severe sensorineural hearing loss caused by lightning.

    Science.gov (United States)

    Myung, Nam-Suk; Lee, Il-Woo; Goh, Eui-Kyung; Kong, Soo-Keun

    2012-01-01

    Lightning strike can produce an array of clinical symptoms and injuries. It may damage multiple organs and cause auditory injuries ranging from transient hearing loss and vertigo to complete disruption of the auditory system. Tympanic-membrane rupture is relatively common in patients with lightning injury. The exact pathogenetic mechanisms of auditory lesions in lightning survivors have not been fully elucidated. We report the case of a 45-year-old woman with bilateral profound sensorineural hearing loss caused by a lightning strike, who was successfully rehabilitated after a cochlear implantation. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. A rare cause of severe hepatomegaly with an improving outcome

    DEFF Research Database (Denmark)

    Godskesen, Line Elberg; Abildgaard, Niels; Kjeldsen, Jens

    2014-01-01

    A previously healthy 43-year-old man presented with dyspnoea, 15 kg weight loss, severe hepatomegaly and alkaline phosphatase at 5400 U/L. Examinations seemed to suggest cirrhosis, but blood samples did not show any signs of underlying liver disease. Liver biopsy revealed amyloid light chain (AL...

  15. Defective immuno- and thymoproteasome assembly causes severe immunodeficiency

    DEFF Research Database (Denmark)

    Treise, Irina; Huber, Eva M.; Klein-Rodewald, Tanja

    2018-01-01

    By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results...

  16. Hormonal Treatment for Severe Hydronephrosis Caused by Bladder Endometriosis

    Directory of Open Access Journals (Sweden)

    Erkan Efe

    2014-01-01

    Full Text Available The incidence of endometriosis cases involving the urinary system has recently increased, and the bladder is a specific zone where endometriosis is most commonly seen in the urinary system. In the case presented here, a patient presented to the emergency department with the complaint of side pain and was examined and diagnosed with severe hydronephrosis and bladder endometriosis was determined in the etiology. After the patient was pathologically diagnosed, Levonorgestrel-Releasing Intrauterine System (LNG-IUS was administered to the uterine cavity. At the 12-month follow-up, endometriosis was not observed in the cystoscopy and symptoms had completely regressed. Hydronephrosis may be observed after exposure of the ureter, and silent renal function loss may develop in patients suffering from endometriosis with bladder involvement. For patients with moderate or severe hydronephrosis associated with bladder endometriosis, LNG-IUS application may be separately and successfully used after conservative surgery.

  17. Causes of several accidents in gamma radiography testing units

    International Nuclear Information System (INIS)

    Vykrocil, L.

    1979-01-01

    Three cases are described of radiation accidents in gamma flaw-detection work-places in the West Bohemian Region. The causes of the accidents stemmed from the unsatisfactory technical condition of the materials testing equipment used and nonobservance of regulations for work with radioactive sourr.es. It is necessary for precluding similar accident to improve preventive care of gamma flaw-detection equipment and to educate personnel who would be considered for coping with the situation when control over the radiation source is lost. (Ha)

  18. Permanent make-up colorants may cause severe skin reactions.

    Science.gov (United States)

    Wenzel, Sabrina M; Welzel, Julia; Hafner, Christian; Landthaler, Michael; Bäumler, Wolfgang

    2010-10-01

    In recent years, cosmetic tattoos [permanent make-up (PMU)] on eyelids, eyebrows and lips have become increasingly popular. However, most colorants are manufactured for non-medical purposes, without any established history of safe use in humans. To investigate severe adverse reactions, such as swelling, burning, and the development of papules, of the lips and the surrounding area in 4 patients who had had at least two PMU procedures on their lips. Adverse skin reactions were examined with patch and prick testing of the colorants. In addition, skin biopsies were taken in the centre of the prick test for histology. One patient declined prick testing. Beauticians tended to use various PMU products, but all contained Pigment Red 181 (CI 73360). All patients tested showed a clear delayed reaction to Pigment Red 181 or the tattoo ink, or both, after prick testing. Histology indicated an allergic reaction. Each lip lesion slowly abated after several months of topical or systemic therapy with steroids in combination with tacrolimus, but none has yet completely resolved. In light of the severe and often therapy-resistant skin reactions, we strongly recommend the regulation and control of the substances used in PMU colorants. © 2010 John Wiley & Sons A/S.

  19. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita.

    Science.gov (United States)

    Walne, Amanda J; Vulliamy, Tom; Kirwan, Michael; Plagnol, Vincent; Dokal, Inderjeet

    2013-03-07

    Dyskeratosis congenita (DC) and its phenotypically severe variant, Hoyeraal-Hreidarsson syndrome (HHS), are multisystem bone-marrow-failure syndromes in which the principal pathology is defective telomere maintenance. The genetic basis of many cases of DC and HHS remains unknown. Using whole-exome sequencing, we identified biallelic mutations in RTEL1, encoding a helicase essential for telomere maintenance and regulation of homologous recombination, in an individual with familial HHS. Additional screening of RTEL1 identified biallelic mutations in 6/23 index cases with HHS but none in 102 DC or DC-like cases. All 11 mutations in ten HHS individuals from seven families segregated in an autosomal-recessive manner, and telomere lengths were significantly shorter in cases than in controls (p = 0.0003). This group had significantly higher levels of telomeric circles, produced as a consequence of incorrect processing of telomere ends, than did controls (p = 0.0148). These biallelic RTEL1 mutations are responsible for a major subgroup (∼29%) of HHS. Our studies show that cells harboring these mutations have significant defects in telomere maintenance, but not in homologous recombination, and that incorrect resolution of T-loops is a mechanism for telomere shortening and disease causation in humans. They also demonstrate the severe multisystem consequences of its dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  20. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.

    Science.gov (United States)

    Huizing, Marjan; Scher, Charles D; Strovel, Erin; Fitzpatrick, Diana L; Hartnell, Lisa M; Anikster, Yair; Gahl, William A

    2002-02-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease consisting of oculocutaneous albinism and a storage pool deficiency resulting from absent platelet dense bodies. The disorder is genetically heterogeneous. The majority of patients, including members of a large genetic isolate in northwest Puerto Rico, have mutations in HPS1. Another gene, ADTB3A, was shown to cause HPS-2 in two brothers having compound heterozygous mutations that allowed for residual production of the gene product, the beta3A subunit of adaptor complex-3 (AP-3). This heterotetrameric complex serves as a coat protein-mediating formation of intracellular vesicles, e.g. the melanosome and platelet dense body, from membranes of the trans-Golgi network. We determined the genomic organization of the human ADTB3A gene, with intron/exon boundaries, and describe a third patient with beta3A deficiency. This 5-y-old boy has two nonsense mutations, C1578T (R-->X) and G2028T (E-->X), which produce no ADTB3A mRNA and no beta3A protein. The associated mu3 subunit of AP-3 is also entirely absent. In fibroblasts, the cell biologic concomitant of this deficiency is robust and aberrant trafficking through the plasma membrane of LAMP-3, an integral lysosomal membrane protein normally carried directly to the lysosome. The clinical concomitant is a severe, G-CSF-responsive neutropenia in addition to oculocutaneous albinism and platelet storage pool deficiency. Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia.

  1. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.

    2011-01-01

    Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

  2. Role of biosimilars in neutropenia prevention in cancer patients

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-01-01

    Full Text Available Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio® was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN was

  3. Role of biosimilars in neutropenia prevention in cancer patients

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2015-01-01

    Full Text Available Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio® was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN was

  4. Dental findings and treatment in consanguinity associated congenital chronic familial neutropenia.

    Science.gov (United States)

    Buduneli, Nurcan; Cogulu, Dilsah; Kardesler, Levent; Kütükçüler, Necil

    2006-01-01

    The purpose of this report is to describe dental findings and treatment of an 11-year old male patient and a 5-year old female patient, children of first cousins, suffering from severe benign congenital chronic familial neutropenia. This case report emphazises the importance of differential diagnosis of immunodeficiencies including congenital chronic familial neutropenia in the background of severe periodontal diseases and/or diffuse carious lesions in children.

  5. Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-08-05

    TNF blockers have rarely been associated with haematological complications; however, there are scattered case reports of marked neutropenia with their use and necessitating in their withdrawal. We would like to report a series of five patients who developed neutropenia with etanercept use; however, all these patients were re-challenged with etanercept with a mean follow up of 30 months. These patients developed neutropenia within 2 months of starting etanercept. Two patients were eventually taken off etanercept; one of them needed switching to a different form of TNF blockers, and the second patient is in clinical remission with low-dose corticosteroids. All our patients continued to have mild-moderate degree of neutropenia; however, they are being monitored very closely and they are enjoying complete disease remission. It was interesting to note that none of our patients had increased infections during the re-challenge phase, even though they had grade 2 to grade 4 neutropenia. We have re-challenged these patients without any clinical complications, revealing that patients with mild to moderate neutropenia can be safely exposed to TNF blockers as long as they are monitored with regular cell count checks. Although largely noted to be clinically insignificant in our patient series, the potential of drug-induced neutropenia in causing higher rate of infections do exist. Careful clinical and hematologic monitoring is the best way to recognize this adverse event.

  6. Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases.

    Science.gov (United States)

    Weycker, Derek; Sofrygin, Oleg; Seefeld, Kim; Deeter, Robert G; Legg, Jason; Edelsberg, John

    2013-02-13

    Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77). Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

  7. Neutropenia febril: convertir el bajo riesgo en cero riesgo To convert the low risk in zero risk in patients with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Alberto Arencibia Núñez

    2009-08-01

    Full Text Available La neutropenia febril constituye una de las principales causas de morbiletalidad en los pacientes con hemopatías malignas; sin embargo, la presentación clínica y evolución de esta complicación varía considerablemente de un paciente a otro. El primer modelo de estratificación de riesgo fue desarrollado por Talcot a partir de elementos clínicos y diferenciaba a los pacientes según el riesgo de presentar complicaciones letales. No obstante, cerca del 10 % de los pacientes catalogados como de bajo riesgo de complicaciones graves requieren tratamiento intrahospitalario. La determinación de algunos reactantes de fase aguda como la proteína C reactiva, las interleucinas 6 y 8 y la procalcitonina, aumentan notablemente la sensibilidad y especificidad de los modelos pronósticos. Las nuevas técnicas imagenológicas y de biología molecular facilitarán el diagnóstico precoz y certero de las infecciones en un futuro cercano. Sin embargo, es necesario desarrollar modelos pronósticos que combinen elementos clínicos y humorales adaptados a las condiciones epidemiológicas de cada centro, para optimizar el tratamiento diferenciado de los enfermos con neutropenia febril.Febrile neutropenia is one of the main causes of mortality in patients presenting with malignant hemopathic disorders; however the clinical and course presentation of this condition differ notably between patients. The first risk stratification model was developed by Talcot from clinical elements and differentiated the patients according the risk of lethal complications. However, around the 10% of patients classed as low risk of severe complications required intrahospital treatment. The determination of some acute phase reactants e.g. reactive C protein, 6 and 8 interleukins, and procalcitonin, increases remarkably the sensitivity and specificity of prognostic model. The new imaging techniques and of molecular biology allow an early and accurate diagnosis of infections in a near

  8. A "high severity" spruce beetle outbreak in Wyoming causes moderate-severity carbon cycle perturbations

    Science.gov (United States)

    Berryman, E.; Frank, J. M.; Speckman, H. N.; Bradford, J. B.; Ryan, M. G.; Massman, W. J.; Hawbaker, T. J.

    2017-12-01

    Bark beetle outbreaks in Western North American forests are often considered a high-severity disturbance from a carbon (C) cycling perspective, but field measurements that quantify impacts on C dynamics are very limited. Often, factors out of the researcher's control complicate the separation of beetle impacts from other drivers of C cycling variability and restrict statistical inference. Fortuitously, we had four years of pre-spruce beetle outbreak C cycle measurements in a subalpine forest in southeastern Wyoming (Glacier Lakes Ecosystem Experiments Site, or GLEES) and sustained intermittent monitoring for nearly a decade after the outbreak. Here, we synthesize published and unpublished pre- and post-outbreak measurements of key C cycle stocks and fluxes at GLEES. Multiple lines of evidence, including chamber measurements, eddy covariance measurements, and tracking of soil and forest floor C pools over time, point to the GLEES outbreak as a moderate-severity disturbance for C loss to the atmosphere, despite 70% to 80% of overstory tree death. Reductions in NEE were short-lived and the forest quickly returned to a carbon-neutral state, likely driven by an uptick in understory growth. Effect of mortality on the C cycle was asymmetrical, with a 50% reduction in net carbon uptake (NEE) two years into the outbreak, yet no measureable change in either ecosystem or growing season soil respiration. A small pulse in soil respiration occurred but was only detectable during the winter and amounted to < 10% of NEE. Possible reasons for the lack of measureable respiration response are discussed with emphasis on lessons learned for monitoring and modeling future outbreaks. We suggest a comprehensive assessment and definition of "moderate-severity" disturbances for Western forests and suggest that all tree mortality events may not be high-severity when it comes to C fluxes.

  9. Secondary Infections in Cancer Patients with Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    Alpay Azap

    2012-09-01

    Full Text Available OBJECTIVE: Patients with neutropenia due to cancer chemotherapy are prone to severe infections. Cancer patients can experience >1 infectious episode during the same period of neutropenia. This study aimed to determine the etiological and clinical characteristics of secondary infectious episodes in cancer patients with febrile neutropenia and to identify the factors associated with the risk of secondary infectious episodes. METHODS: All cancer patients that received antineoplastic chemotherapy at Ankara University, School of Medicine, Department of Hematology between May 2004 and May 2005 and developed neutropenia were included in the study. Data were collected using survey forms that were completed during routine infectious diseases consultation visits. Categorical data were analyzed using the chi-square test, whereas Student’s t-test was used for continuous variables. Multivariate logistic regression analysis was performed to identify independent predictors of secondary infections (SIs. RESULTS: SIs were observed during 138 (53% of 259 febrile neutropenic episodes. Of the 138 episodes, 89 (64.5% occurred in male patients with a mean age of 40.9 years (range: 17-76 years. In total, 80% of the SIs were clinically or microbiologically documented. Factors on d 4 of the initial febrile episode were analyzed via a logistic regression model. The presence of a central intravenous catheter (OR: 3.01; P < 0.001, acute myeloid leukemia (AML as the underlying disease (OR: 2.12; P = 0.008, diarrhea (OR: 4.59; P = 0.005, and invasive aspergillosis (IA during the initial febrile episode (OR: 3.96; P = 0.009 were statistically significant risk factors for SIs. CONCLUSION: Among the cancer patients with neutropenia in the present study, AML as the underlying disease, the presence of a central venous catheter, diarrhea, and IA during the initial febrile episode were risk factors for the development of SIs.

  10. Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

    Science.gov (United States)

    Li, Wentao; Kwok, Carol Chi-Hei; Chan, Dominic Chun-Wan; Wang, Feng; Tse, Lap Ah

    2018-04-01

    Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

  11. Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients

    Directory of Open Access Journals (Sweden)

    Guariglia R

    2016-01-01

    Full Text Available Roberto Guariglia,1 Maria Carmen Martorelli,1 Rosa Lerose,2 Donatella Telesca,2 Maria Rita Milella,2 Pellegrino Musto3 1Unit of Hematology and Stem Cell Transplantation, 2Pharmacy Service, 3Scientific Direction, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Potenza, Italy Abstract: Neutropenia and febrile neutropenia (FN are frequent and potentially fatal toxicities of myelosuppressive anticancer treatments. The introduction of granulocyte colony-stimulating factors (G-CSFs in clinical practice has remarkably reduced the duration and severity of neutropenia, as well as the incidence of FN, thus allowing the administration of chemotherapeutic agents at the optimal dose and time with lower risk. The current scenario of G-CSFs in Europe includes filgrastim, lenograstim, some G-CSF biosimilars, and pegfilgrastim. Recently, a novel long-acting G-CSF, lipegfilgrastim, became available. Lipegfilgrastim is a glycopegylated G-CSF, alternative to pegfilgrastim, and has shown in randomized trials, to be equivalent to pegfilgrastim in reducing the incidence of severe neutropenia and FN in patients with breast cancer receiving chemotherapy, with a similar safety profile. Furthermore, lipegfilgrastim was more effective than the placebo in reducing the incidence of severe neutropenia, its duration, and time to absolute neutrophil count recovery, in patients with non-small cell lung cancer receiving myelosuppressive therapy. Although the number of studies currently published is still limited, lipegfilgrastim seems to be a promising drug in the management of chemotherapy-induced neutropenia. Keywords: neutropenia, febrile neutropenia, granulocyte colony-stimulating factors, G-CSF, pegfilgrastim, lipegfilgrastim

  12. Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Jun Osugi

    2016-01-01

    Full Text Available Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.

  13. Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

    Energy Technology Data Exchange (ETDEWEB)

    Ruysscher, D. de [MAASTRO Clinic, Maastricht (Netherlands). Dept. of Radiation Oncology; Meerbeeck, J. van [Ghent Univ. Hospital (Belgium). Dept. of Respiratory Medicine; Vandecasteele, K. [Ghent Univ. Hospital (BE). Dept. of Radiation Oncology] (and others)

    2012-07-15

    Background: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. Methods and patients: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Results: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). Conclusion: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus

  14. Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

    International Nuclear Information System (INIS)

    Ruysscher, D. de; Meerbeeck, J. van; Vandecasteele, K.

    2012-01-01

    Background: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. Methods and patients: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Results: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). Conclusion: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus

  15. Mutations in the G6PC3 gene cause Dursun syndrome.

    Science.gov (United States)

    Banka, Siddharth; Newman, William G; Ozgül, R Koksal; Dursun, Ali

    2010-10-01

    Dursun syndrome is a triad of familial primary pulmonary hypertension, leucopenia, and atrial septal defect. Here we demonstrate that mutations in G6PC3 cause Dursun syndrome. Mutations in G6PC3 are known to also cause severe congenital neutropenia type 4. Identification of the genetic basis of Dursun syndrome expands the pre-existing knowledge about the phenotypic effects of mutations in G6PC3. We propose that Dursun syndrome should now be considered as a subset of severe congenital neutropenia type 4 with pulmonary hypertension as an important clinical feature. Copyright © 2010 Wiley-Liss, Inc.

  16. Severe hypoglycaemia requiring the assistance of emergency medical services - frequency, causes and symptoms

    Czech Academy of Sciences Publication Activity Database

    Krnačová, V.; Kuběna, Aleš Antonín; Macek, K.; Bezděk, M.; Šmahelová, A.; Vlček, J.

    2012-01-01

    Roč. 156, č. 3 (2012), s. 271-277 ISSN 1213-8118 Grant - others:GA UK(CZ) SVV-2010-261-004 Keywords : regression trees * causes * symptoms * incidence * emergency medical service * severe hypoglycaemia Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.990, year: 2012 http://library.utia.cas.cz/separaty/2013/E/kubena-severe hypoglycaemia requiring the assistance of emergency medical services - frequency causes and symptoms.pdf

  17. A case of fetal intestinal volvulus without malrotation causing severe anemia.

    Science.gov (United States)

    Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika

    2015-01-01

    Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention.

  18. A Case of Fetal Intestinal Volvulus without Malrotation Causing Severe Anemia

    Directory of Open Access Journals (Sweden)

    Tomoko Nakagawa

    2015-01-01

    Full Text Available Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention.

  19. Human error as the root cause of severe accidents at nuclear reactors

    International Nuclear Information System (INIS)

    Kovács Zoltán; Rýdzi, Stanislav

    2017-01-01

    A root cause is a factor inducing an undesirable event. It is feasible for root causes to be eliminated through technological process improvements. Human error was the root cause of all severe accidents at nuclear power plants. The TMI accident was caused by a series of human errors. The Chernobyl disaster occurred after a badly performed test of the turbogenerator at a reactor with design deficiencies, and in addition, the operators ignored the safety principles and disabled the safety systems. At Fukushima the tsunami risk was underestimated and the project failed to consider the specific issues of the site. The paper describes the severe accidents and points out the human errors that caused them. Also, provisions that might have eliminated those severe accidents are suggested. The fact that each severe accident occurred on a different type of reactor is relevant – no severe accident ever occurred twice at the same reactor type. The lessons learnt from the severe accidents and the safety measures implemented on reactor units all over the world seem to be effective. (orig.)

  20. Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases

    Directory of Open Access Journals (Sweden)

    Weycker Derek

    2013-02-01

    Full Text Available Abstract Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC 9/L, and body temperature ≥38.3°C or receipt of antibiotics and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection. Accuracy was evaluated principally based on positive predictive value (PPV and sensitivity. Results Among 357 study subjects, 82 (23% met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28, PPV was 100% and sensitivity was 34% (95% CI: 24–45. For the definition including neutropenia in the primary position (n=54, PPV was 87% (78–95 and sensitivity was 57% (46–68. For the definition including neutropenia in any position (n=71, PPV was 77% (68–87 and sensitivity was 67% (56–77. Conclusions Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

  1. Different clinical features of anaphylaxis according to cause and risk factors for severe reactions.

    Science.gov (United States)

    Kim, Sang-Yoon; Kim, Min-Hye; Cho, Young-Joo

    2018-01-01

    Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction. Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed. A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively. More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  2. Tyrosine kinase inhibitors therapy related neutropenia and thrombocythopenia correction in CML patients

    Directory of Open Access Journals (Sweden)

    V. A. Shuvaev

    2014-07-01

    Full Text Available At present, introduction of target therapy to chronic myelogenous leukemia (CML treatment made CML not life-limiting disorder. The main condition of treatment efficacy is its continuity. The most common causes of dose reduction and CML therapy interruption is hematologic toxicities such as neutropenia and thrombocytopenia. The adverse events correction in these circumstances is vital. Recommendations for neutropenia and thrombocytopenia correction are proposed in this article. The basement and results of the use of granulocyte colony stimulating factor (G-CSF and thrombopoietine receptor agonist for hematologic toxicities correction with clinical case are presented.

  3. Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.

    Science.gov (United States)

    Sella, Ruti; Flomenblit, Lena; Goldstein, Itamar; Kaplinsky, Chaim

    2010-02-01

    Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN is characterized by neutrophil count familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded. Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods. The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective tool for clinical decision making.

  4. Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia.

    Science.gov (United States)

    Murphy, Heidi; Patrick, Jessica; Báez-Irizarry, Eileen; Lacassie, Yves; Gómez, Ricardo; Vargas, Alfonso; Barkemeyer, Brian; Kanotra, Sohit; Zambrano, Regina M

    2016-04-01

    Neonatal severe hyperparathyroidism (NSHPT) is a rare, life-threatening condition that presents with severe hypercalcemia, hyperparathyroidism, and osteopenia in the newborn period. Treatment of NSHPT traditionally includes hydration and bisphosphonates; however newer calcimimetic agents, such as cinacalcet, are now being utilized to prevent or delay parathyroidectomy which is technically difficult in the newborn. Medical treatment success is related to calcium sensing receptor (CaSR) genotype. We report a 4-day-old infant who presented with hyperbilirubinemia, poor feeding, weight loss, severe hypotonia and was ultimately diagnosed with NSHPT. The patient's total serum calcium level of 36.8 mg/dL (reference range: 8.5-10.4 mg/dL) is, to our knowledge, the highest ever documented in this setting. Exome data previously obtained on the infant's parents was re-analyzed demonstrating bi-parental heterozygosity for a mutation of the CASR gene: c.206G > A, and Sanger sequencing data confirmed the patient was a homozygote for the same mutation. Though a patient with the same CaSR gene mutation described here has responded to cinacalcet, our patient did not respond and required parathyroidectomy. Though this case has previously been published as a surgical case report, a full report of the medical management and underlying genetic etiology is warranted; this case underscores the importance of disclosing bi-parental heterozygosity for a gene causing severe neonatal disease particularly when treatment is available and illustrates the need for further in vitro studies of this CaSR mutation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

    Science.gov (United States)

    Versluis, A; Knulst, A C; Kruizinga, A G; Michelsen, A; Houben, G F; Baumert, J L; van Os-Medendorp, H

    2015-02-01

    Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary. © 2014 John Wiley & Sons Ltd.

  6. LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood

    NARCIS (Netherlands)

    Michot, Caroline; Hubert, Laurence; Brivet, Michèle; de Meirleir, Linda; Valayannopoulos, Vassili; Müller-Felber, Wolfgang; Venkateswaran, Ramesh; Ogier, Hélène; Desguerre, Isabelle; Altuzarra, Cécilia; Thompson, Elizabeth; Smitka, Martin; Huebner, Angela; Husson, Marie; Horvath, Rita; Chinnery, Patrick; Vaz, Frederic M.; Munnich, Arnold; Elpeleg, Orly; Delahodde, Agnès; de Keyzer, Yves; de Lonlay, Pascale

    2010-01-01

    Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid

  7. Management of Febrile Neutropenia in Patients receiving ...

    African Journals Online (AJOL)

    BACKGROUND: One in ten patients on anticancer medication will develop febrile neutropenia irrespective of tumour type. There is need to protect our patients from this fatal condition while optimising chemotherapy. This may be difficult for a poor country. OBJECTIVE: To assess the management of cancer patients with

  8. Risk assessment in fever and neutropenia in children with cancer : What did we learn?

    NARCIS (Netherlands)

    Poele, Esther M. te; Tissing, Wim J. E.; Kamps, Willem A.; de Bont, Eveline S. J. M.

    2009-01-01

    Children with cancer treated with chemotherapy are susceptible to bacterial infections and serious infectious complications. However, fever and neutropenia can also result from other causes, for which no antibiotic treatment is needed. In the past decades attempts have been made to stratify the

  9. Regional Variations in the Risk and Severity of Ciguatera Caused by Eating Moray Eels.

    Science.gov (United States)

    Chan, Thomas Y K

    2017-06-26

    Moray eels ( Gymnothorax species) from tropical waters have long been known to be high-risk species, and the consumption of particularly the viscera or ungutted eels can result in severe ciguatera (known as Gymnothorax or moray eel poisoning), characterized by prominent neurological features. In this review, the main objective was to describe the risk and severity of ciguatera caused by eating moray eels in different parts of the world. Moray eels can accumulate very high ciguatoxin (CTX) levels in the flesh and particularly the liver. Therefore, even the smaller ones can be toxic and the consumption of an average portion (particularly liver) can result in severe or fatal ciguatera. Moray eels (particularly when ungutted) must never be served in gatherings since they can cause mass poisoning because of their large sizes and high CTX levels. Apart from regulatory measures restricting or excluding access, the public should be repeatedly warned to avoid eating moray eels.

  10. Regional Variations in the Risk and Severity of Ciguatera Caused by Eating Moray Eels

    Directory of Open Access Journals (Sweden)

    Thomas Y. K. Chan

    2017-06-01

    Full Text Available Moray eels (Gymnothorax species from tropical waters have long been known to be high-risk species, and the consumption of particularly the viscera or ungutted eels can result in severe ciguatera (known as Gymnothorax or moray eel poisoning, characterized by prominent neurological features. In this review, the main objective was to describe the risk and severity of ciguatera caused by eating moray eels in different parts of the world. Moray eels can accumulate very high ciguatoxin (CTX levels in the flesh and particularly the liver. Therefore, even the smaller ones can be toxic and the consumption of an average portion (particularly liver can result in severe or fatal ciguatera. Moray eels (particularly when ungutted must never be served in gatherings since they can cause mass poisoning because of their large sizes and high CTX levels. Apart from regulatory measures restricting or excluding access, the public should be repeatedly warned to avoid eating moray eels.

  11. Regional Variations in the Risk and Severity of Ciguatera Caused by Eating Moray Eels

    Science.gov (United States)

    Chan, Thomas Y. K.

    2017-01-01

    Moray eels (Gymnothorax species) from tropical waters have long been known to be high-risk species, and the consumption of particularly the viscera or ungutted eels can result in severe ciguatera (known as Gymnothorax or moray eel poisoning), characterized by prominent neurological features. In this review, the main objective was to describe the risk and severity of ciguatera caused by eating moray eels in different parts of the world. Moray eels can accumulate very high ciguatoxin (CTX) levels in the flesh and particularly the liver. Therefore, even the smaller ones can be toxic and the consumption of an average portion (particularly liver) can result in severe or fatal ciguatera. Moray eels (particularly when ungutted) must never be served in gatherings since they can cause mass poisoning because of their large sizes and high CTX levels. Apart from regulatory measures restricting or excluding access, the public should be repeatedly warned to avoid eating moray eels. PMID:28672845

  12. Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    An-Shine Chao

    2009-01-01

    Full Text Available We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebral artery was 0.8 m/s, indicating severe fetal anemia. Multiple intrauterine transfusions for the anemic fetus were administered. However, persistent severe fetal anemia and placentomegaly caused poor neonatal death and mirror syndrome in the mother. Uncommon red blood cell alloimmunization has to be watched for early in any population, especially in a woman with a history of unexplained perinatal loss.

  13. [Cause analysis and management of severe dislocated or subluxated intraocular lenses in the capsular bag].

    Science.gov (United States)

    Wang, Wen-qing; Jia, Li-Li; Lu, Bin; Fang, Jian; Chen, Ying

    2006-05-01

    To analyze the causes of severe dislocated and subluxated intraocular lenses (IOL) in capsular bag and the relevancy with abnormal capsular constitution. The abnormality of capsular and the position of IOL were retrospectively analyzed by slit lamp and microscope in dilated pupil. Surgeries were performed in all of 31 cases in order to exchange or reposit the dislocated or subluxated lOL. Among 31 cases, there were 20 cases with the dislocated or subluxated IOL in the earlier postoperative period and 11 cases in the later postoperative period. The subluxated IOL in 5 cases (16.1%) were caused by the large rupture of the posterior capsular, and by the rupture of the posterior capsular in 9 cases (29.0%). A upward subluxated IOL developed in one case (3.2%) as the result of small rupture in the equater capsular. The subluxatd IOL in the anterior chamber in two cases (6.5%) was induced by the radial rupture of residual anterior capsular. The size of the IOLs in 2 cases were not matched to the diameter of the capsule bag. The dislocated IOL into the vitreous in 2 cases was caused by the rupture of the superior capsular. The subluxated IOL in 2 cases (6.5%) was caused by the zonal finers rupture due to trauma. The severe disfiguration of the IOL haptic was found in one case. The dislocated IOL in 6 cases (19.4%) was caused by asymmetric capsular shrinkage. A subluxated IOL in one case was resulted from the zonular defects with pseudoexfoliation syndrome. The postoperative corrected visual acuity was 0.5 - 1.0 in 24 eyes, 0.1 - 0.4 in 6 eyes, and 0.05 in one eye. There are several causes for the dislocated or subluxated IOL. The correction of the IOL position should depend on the cause for the dislocated or subluxated IOL.

  14. Viral findings in adult hematological patients with neutropenia.

    Directory of Open Access Journals (Sweden)

    Lars Ohrmalm

    Full Text Available BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159 were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22% and NPA (18% with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL (p<0.01 and patients with fever (p<0.001 were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.

  15. Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis.

    Science.gov (United States)

    Guirl, Michael J; Högenauer, Christoph; Santa Ana, Carol A; Porter, Jack L; Little, Katherine H; Stone, Marvin J; Fordtran, John S

    2003-10-01

    The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

  16. Traumatic retropharyngeal emphysema as a cause for severe respiratory distress in a newborn

    International Nuclear Information System (INIS)

    Barlev, Dan M.; Nagourney, Beth A.; Saintonge, Ronald

    2003-01-01

    Traumatic injury to the pharynx or esophagus in a newborn from intubation or tube suctioning may have various presentations. Difficulty passing a gastric tube or feeding problems may erroneously suggest the diagnosis of esophageal atresia. Associated respiratory distress may be caused by pneumothorax or pleural effusion if the pleural space is entered. We report the case of a full-term newborn presenting with severe respiratory distress caused by a large retropharyngeal air collection resulting from hypopharyngeal perforation from prior intubation and suctioning. Chest abnormality, sufficient to account for the degree of respiratory distress, was not demonstrated. (orig.)

  17. Severe hemorrhage from the umbilical cord at birth: a preventable cause of neonatal shock.

    Science.gov (United States)

    Singh, Neetu; Suresh, Gautham

    2013-01-01

    Posthemorrhagic anemia is a rare but important cause of anemia in neonates, second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia are reported from fetomaternal hemorrhage or umbilical cord accidents in utero. This case report describes a preterm infant who developed severe anemia and shock immediately after delivery related to an acute hemorrhage through patent umbilical cord vessels secondary to a tear in the umbilical cord at the site of cord clamping. We believe that umbilical cord bleeding from errors in cord clamping could be an important cause of acute blood loss in the delivery room and that it may result in significant clinical morbidity, especially in extremely premature infants.

  18. CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria

    DEFF Research Database (Denmark)

    Saunders, Carol; Smith, Laurie; Wibrand, Flemming

    2015-01-01

    of type IV 3-MGA-uria characterized by cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, and death in early childhood. Four of the individuals were of Greenlandic descent, and one was North American, of Northern European and Asian descent...

  19. Mortality caused by intracranial bleeding in non-severe hemophilia A patients.

    Science.gov (United States)

    Loomans, J I; Eckhardt, C L; Reitter-Pfoertner, S E; Holmström, M; van Gorkom, B Laros; Leebeek, F W G; Santoro, C; Haya, S; Meijer, K; Nijziel, M R; van der Bom, J G; Fijnvandraat, K

    2017-06-01

    Essentials Data on bleeding-related causes of death in non-severe hemophilia A (HA) patients are scarce. Such data may provide new insights into areas of care that can be improved. Non-severe HA patients have an increased risk of dying from intracranial bleeding. This demonstrates the need for specialized care for non-severe HA patients. Background Non-severe hemophilia (factor VIII concentration [FVIII:C] of 2-40 IU dL -1 ) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on bleeding-related causes of death, such as fatal intracranial bleeding, in non-severe patients are scarce. Such data may provide new insights into areas of care that can be improved. Aims To describe mortality rates, risk factors and comorbidities associated with fatal intracranial bleeding in non-severe hemophilia A patients. Methods We analyzed data from the INSIGHT study, an international cohort study of all non-severe hemophilia A patients treated with FVIII concentrates during the observation period between 1980 and 2010 in 34 participating centers across Europe and Australia. Clinical data and vital status were collected from 2709 patients. We report the standardized mortality rate for patients who suffered from fatal intracranial bleeding, using a general European male population as a control population. Results Twelve per cent of the 148 deceased patients in our cohort of 2709 patients died from intracranial bleeding. The mortality rate between 1996 and 2010 for all ages was 3.5-fold higher than that in the general population (95% confidence interval [CI] 2.0-5.8). Patients who died from intracranial bleeding mostly presented with mild hemophilia without clear comorbidities. Conclusion Non-severe hemophilia A patients have an increased risk of dying from intracranial bleeding in comparison with the general population. This demonstrates the

  20. Severe Hemorrhage from the Umbilical Cord at Birth: A Preventable Cause of Neonatal Shock

    OpenAIRE

    Singh, Neetu; Suresh, Gautham

    2013-01-01

    Posthemorrhagic anemia is a rare but important cause of anemia in neonates, second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia are reported from fetomaternal hemorrhage or umbilical cord accidents in utero. This case report describes a preterm infant who developed severe anemia and shock immediately after delivery related to an acute hemorrhage through patent umbilical cord vessels secondary to a tear in the umbilical cord at the site of cord clamping. We believe...

  1. Case of severe intestinal complications caused by high dose-rate intracavitary irradiation for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Kenji; Nishikawa, Kiyoshi; Matsuki, Kazuhiko; Watanabe, Katsushi

    1987-02-01

    A 46-year-old woman with severe intestinal complication caused by high dose-rate intracavitary irradiation is reported. She received radiation treatment of stage IIb cervical cancer between July 24 and September 26, 1984: a dose of 2400 rad to a point A concurrently with 2000 rad to the parametrium following 4000 rad to the whole pelvis. Eight months later she developed diarrhea and bloody stool. Barium enema study revealed a stenosis at 20 to 25 cm from the anal ring and romanoscopy oozing coagula at the same site. On November 29, 1985 transverse colostomy was performed because of continuing bloody stool and abdominal pain. On January 30, 1986 resection of the ileum and ileostomy were done because of the ileum perforation located 26 cm apart from the ileum end. Some discussion on the causes of this complication are made, suggesting that short length of a tandem and deep location of ovoids influence its cause.

  2. G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

    Science.gov (United States)

    Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

    2004-02-01

    Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

  3. Root causes and impacts of severe accidents at large nuclear power plants.

    Science.gov (United States)

    Högberg, Lars

    2013-04-01

    The root causes and impacts of three severe accidents at large civilian nuclear power plants are reviewed: the Three Mile Island accident in 1979, the Chernobyl accident in 1986, and the Fukushima Daiichi accident in 2011. Impacts include health effects, evacuation of contaminated areas as well as cost estimates and impacts on energy policies and nuclear safety work in various countries. It is concluded that essential objectives for reactor safety work must be: (1) to prevent accidents from developing into severe core damage, even if they are initiated by very unlikely natural or man-made events, and, recognizing that accidents with severe core damage may nevertheless occur; (2) to prevent large-scale and long-lived ground contamination by limiting releases of radioactive nuclides such as cesium to less than about 100 TBq. To achieve these objectives the importance of maintaining high global standards of safety management and safety culture cannot be emphasized enough. All three severe accidents discussed in this paper had their root causes in system deficiencies indicative of poor safety management and poor safety culture in both the nuclear industry and government authorities.

  4. Root Causes and Impacts of Severe Accidents at Large Nuclear Power Plants

    International Nuclear Information System (INIS)

    Hoegberg, Lars

    2013-01-01

    The root causes and impacts of three severe accidents at large civilian nuclear power plants are reviewed: the Three Mile Island accident in 1979, the Chernobyl accident in 1986, and the Fukushima Daiichi accident in 2011. Impacts include health effects, evacuation of contaminated areas as well as cost estimates and impacts on energy policies and nuclear safety work in various countries. It is concluded that essential objectives for reactor safety work must be: (1) to prevent accidents from developing into severe core damage, even if they are initiated by very unlikely natural or man-made events, and, recognizing that accidents with severe core damage may nevertheless occur; (2) to prevent large-scale and long lived ground contamination by limiting releases of radioactive nuclides such as cesium to less than about 100 TBq. To achieve these objectives the importance of maintaining high global standards of safety management and safety culture cannot be emphasized enough. All three severe accidents discussed in this paper had their root causes in system deficiencies indicative of poor safety management and poor safety culture in both the nuclear industry and government authorities

  5. Root Causes and Impacts of Severe Accidents at Large Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hoegberg, Lars

    2013-04-15

    The root causes and impacts of three severe accidents at large civilian nuclear power plants are reviewed: the Three Mile Island accident in 1979, the Chernobyl accident in 1986, and the Fukushima Daiichi accident in 2011. Impacts include health effects, evacuation of contaminated areas as well as cost estimates and impacts on energy policies and nuclear safety work in various countries. It is concluded that essential objectives for reactor safety work must be: (1) to prevent accidents from developing into severe core damage, even if they are initiated by very unlikely natural or man-made events, and, recognizing that accidents with severe core damage may nevertheless occur; (2) to prevent large-scale and long lived ground contamination by limiting releases of radioactive nuclides such as cesium to less than about 100 TBq. To achieve these objectives the importance of maintaining high global standards of safety management and safety culture cannot be emphasized enough. All three severe accidents discussed in this paper had their root causes in system deficiencies indicative of poor safety management and poor safety culture in both the nuclear industry and government authorities.

  6. All-Cause and Acute Pancreatitis Health Care Costs in Patients With Severe Hypertriglyceridemia.

    Science.gov (United States)

    Rashid, Nazia; Sharma, Puza P; Scott, Ronald D; Lin, Kathy J; Toth, Peter P

    2017-01-01

    The aim of this study was to assess health care utilization and costs related to acute pancreatitis (AP) in patients with severe hypertriglyceridemia (sHTG) levels. Patients with sHTG levels 1000 mg/dL or higher were identified from January 1, 2007, to June 30, 2013. The first identified incident triglyceride level was labeled as index date. All-cause, AP-related health care visits, and mean total all-cause costs in patients with and without AP were compared during 12 months postindex. A generalized linear model regression was used to compare costs while controlling for patient characteristics and comorbidities. Five thousand five hundred fifty sHTG patients were identified, and 5.4% of these patients developed AP during postindex. Patients with AP had significantly (P < 0.05) more all-cause outpatient visits, hospitalizations, longer length of stays during the hospital visits, and emergency department visits versus patients without AP. Mean (SD) unadjusted all-cause health care costs in the 12 months postindex were $25,343 ($33,139) for patients with AP compared with $15,195 ($24,040) for patients with no AP. The regression showed annual all-cause costs were 49.9% higher (P < 0.01) for patients with AP versus without AP. Patients who developed AP were associated with higher costs; managing patients with sHTG at risk of developing AP may help reduce unnecessary costs.

  7. Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited Women.

    Science.gov (United States)

    Elhassan, Yasir S; Idkowiak, Jan; Smith, Karen; Asia, Miriam; Gleeson, Helena; Webster, Rachel; Arlt, Wiebke; O'Reilly, Michael W

    2018-03-01

    Androgen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and severity of androgen excess that should be considered predictive of non-PCOS pathology. We examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess. Retrospective review of all women undergoing serum androgen measurement at a large tertiary referral center between 2012 and 2016. Serum A4 and T were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased serum androgen underwent phenotyping by clinical notes review. In 1205 women, DHEAS, A4, and T were measured simultaneously. PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n = 15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4 (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were caused by ACC and severe T excess equally by ACC and OHT. Pattern and severity of androgen excess are important predictors of non-PCOS pathology and may be used to guide further investigations as appropriate.

  8. Ela2 mutations and clinical manifestations in familial congenital neutropenia.

    Science.gov (United States)

    Shiohara, Masaaki; Shigemura, Tomonari; Saito, Shoji; Tanaka, Miyuki; Yanagisawa, Ryu; Sakashita, Kazuo; Asada, Hiroshi; Ishii, Eizaburo; Koike, Kazutoshi; Chin, Motoaki; Kobayashi, Masao; Koike, Kenichi

    2009-05-01

    Three familial cases of each of severe congenital neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation. The contents of the neutrophil-specific granule proteins cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were also analyzed in SCN. Genomic DNA was extracted from the patients' peripheral blood or bone marrow, and the coding sequence of the Ela2 gene was amplified by polymerase chain reaction and subjected to direct sequencing. The contents of antimicrobial peptides were analyzed by flow cytometry. Three cases of familial SCN (P13L, R52P, and S97L), 2 of familial CN (W212stop and P110L), and 1 of sporadic SCN (V72M) were shown to have heterozygous mutations in the Ela2 gene. W212stop found in a familial CN case was a novel mutation of Ela2. Prophylactic treatment for growth factors or antibiotic prophylaxis against bacterial infection was useful for lowering the frequency of infectious episodes. Adult patients tended to have less frequent infections compared with minors in the same family. The contents of both cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were significantly reduced in SCN compared with healthy controls. Prophylaxis by growth factor or antibiotics is useful for decreasing risks of bacterial infections in SCN and CN. Adults were likely to have less frequent infections than children in familial cases of SCN and CN with the same mutation of Ela2.

  9. Chloroform ingestion causing severe gastrointestinal injury, hepatotoxicity and dermatitis confirmed with plasma chloroform concentrations.

    Science.gov (United States)

    Jayaweera, Dushan; Islam, Shawkat; Gunja, Naren; Cowie, Chris; Broska, James; Poojara, Latesh; Roberts, Michael S; Isbister, Geoffrey K

    2017-02-01

    Poisoning due to chloroform ingestion is rare. The classic features of acute chloroform toxicity include central nervous system (CNS) and respiratory depression, and delayed hepatotoxicity. A 30-year-old female ingested 20-30 mL of 99% chloroform solution, which caused rapid loss of consciousness, transient hypotension and severe respiratory depression requiring endotracheal intubation and ventilation. She was alert by 12 h and extubated 16 h post-overdose. At 38-h post-ingestion, her liver function tests started to rise and she was commenced on intravenous acetylcysteine. Her alanine transaminase (1283 U/L), aspartate transaminase (734 U/L) and international normalized ratio (2.3) peaked 67- to 72-h post-ingestion. She also developed severe abdominal pain, vomiting and diarrhoea. An abdominal CT scan was consistent with severe enterocolitis, and an upper gastrointestinal endoscopy showed erosive oesophagitis, severe erosive gastritis and ulceration. She was treated with opioid analgesia, proton pump inhibitors, sucralfate and total parenteral nutrition. Secretions caused a contact dermatitis of her face and back. Nine days post-ingestion she was able to tolerate food. Her liver function tests normalized and the dermatitis resolved. Chloroform was measured using headspace gas chromatograph mass spectrometry, with a peak concentration of 2.00 μg/mL, 4 h 20 min post-ingestion. The concentration-time data fitted a 1-compartment model with elimination half-life 6.5 h. In addition to early CNS depression and delayed hepatotoxicity, we report severe gastrointestinal injury and dermatitis with chloroform ingestion. Recovery occurred with good supportive care, acetylcysteine and management of gastrointestinal complications.

  10. Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

    Directory of Open Access Journals (Sweden)

    Turkan Patiroglu

    2014-08-01

    Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

  11. Phenomenological uncertainty analysis of containment building pressure load caused by severe accident sequences

    International Nuclear Information System (INIS)

    Park, S.Y.; Ahn, K.I.

    2014-01-01

    Highlights: • Phenomenological uncertainty analysis has been applied to level 2 PSA. • The methodology provides an alternative to simple deterministic analyses and sensitivity studies. • A realistic evaluation provides a more complete characterization of risks. • Uncertain parameters of MAAP code for the early containment failure were identified. - Abstract: This paper illustrates an application of a severe accident analysis code, MAAP, to the uncertainty evaluation of early containment failure scenarios employed in the containment event tree (CET) model of a reference plant. An uncertainty analysis of containment pressure behavior during severe accidents has been performed for an optimum assessment of an early containment failure model. The present application is mainly focused on determining an estimate of the containment building pressure load caused by severe accident sequences of a nuclear power plant. Key modeling parameters and phenomenological models employed for the present uncertainty analysis are closely related to the in-vessel hydrogen generation, direct containment heating, and gas combustion. The basic approach of this methodology is to (1) develop severe accident scenarios for which containment pressure loads should be performed based on a level 2 PSA, (2) identify severe accident phenomena relevant to an early containment failure, (3) identify the MAAP input parameters, sensitivity coefficients, and modeling options that describe or influence the early containment failure phenomena, (4) prescribe the likelihood descriptions of the potential range of these parameters, and (5) evaluate the code predictions using a number of random combinations of parameter inputs sampled from the likelihood distributions

  12. Impact of socioeconomic deprivation on rate and cause of death in severe mental illness.

    Science.gov (United States)

    Martin, Julie Langan; McLean, Gary; Park, John; Martin, Daniel J; Connolly, Moira; Mercer, Stewart W; Smith, Daniel J

    2014-09-12

    Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated. We aimed to assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations. Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations. Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed.

  13. Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

    Science.gov (United States)

    Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

    2014-12-01

    We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

  14. Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.

    Science.gov (United States)

    Gauthier-Vasserot, Alexandra; Thauvin-Robinet, Christel; Bruel, Ange-Line; Duffourd, Yannis; St-Onge, Judith; Jouan, Thibaud; Rivière, Jean-Baptiste; Heron, Delphine; Donadieu, Jean; Bellanné-Chantelot, Christine; Briandet, Claire; Huet, Frédéric; Kuentz, Paul; Lehalle, Daphné; Duplomb-Jego, Laurence; Gautier, Elodie; Maystadt, Isabelle; Pinson, Lucile; Amram, Daniel; El Chehadeh, Salima; Melki, Judith; Julia, Sophia; Faivre, Laurence; Thevenon, Julien

    2017-01-01

    Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Successful Immunoglobulin Treatment in Severe Cryptogenic Organizing Pneumonia Caused by Dermatomyositis

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    Dong Hoon Lee

    2015-08-01

    Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.

  16. Severe Hemorrhage from the Umbilical Cord at Birth: A Preventable Cause of Neonatal Shock

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    Neetu Singh

    2013-01-01

    Full Text Available Posthemorrhagic anemia is a rare but important cause of anemia in neonates, second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia are reported from fetomaternal hemorrhage or umbilical cord accidents in utero. This case report describes a preterm infant who developed severe anemia and shock immediately after delivery related to an acute hemorrhage through patent umbilical cord vessels secondary to a tear in the umbilical cord at the site of cord clamping. We believe that umbilical cord bleeding from errors in cord clamping could be an important cause of acute blood loss in the delivery room and that it may result in significant clinical morbidity, especially in extremely premature infants.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. First Report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) Causing Severe Disease in Allomyrina dichotoma in Korea

    OpenAIRE

    Lee, Seokhyun; Park, Kwan-Ho; Nam, Sung-Hee; Kwak, Kyu-Won; Choi, Ji-Young

    2015-01-01

    Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is used as a biological control to reduce the pest population. Here, we report for the first time that the OrNV may have landed on Korea and may be the major pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After peroral inoculation, over 60% of infected larvae perished in 6?wk. This viral disease spreads very fast ...

  19. Difference in Neutropenia due to Administration Schedule of TAS-102

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    Yoichiro Yoshida

    2017-03-01

    Full Text Available TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

  20. Incidence, causes, severity and treatment of throat discomfort: a four-region online questionnaire survey.

    Science.gov (United States)

    Addey, Dilys; Shephard, Adrian

    2012-08-10

    Acute sore throat is commonly associated with viral infections. Consumers typically rely on over-the-counter treatments and other remedies to treat symptoms; however, limited information is available regarding consumer perceptions of sore throat or treatment needs. The aim of this study was to investigate perceptions of throat discomfort and how these influence attitudes and consumer behaviour with regard to treatment. Online consumer surveys were completed by participants invited by email between 2003 and 2004 in four markets: the UK, France, Poland, and Malaysia. The questionnaire consisted of 24 questions that covered key issues surrounding throat discomfort including incidence in the past 12 months, causes, severity, effects on functionality and quality of life, actions taken to relieve throat discomfort, the efficacy of these approaches and the reasons behind using specific products. In total, 6465 men and women aged ≥18 years were surveyed, identifying 3514 participants who had suffered throat discomfort/irritation in the past 12 months (response rate of 54%). These participants completed the full survey. The breakdown of throat discomfort sufferers was: UK, 912; France, 899; Poland, 871; Malaysia, 832. A high proportion of respondents experienced one or more instances of throat discomfort in the previous 12 months, with an overall incidence of 54%. Infections including the common cold/influenza and other bacteria/viruses were commonly perceived causes of throat discomfort (72% and 46%, respectively). Physical and environmental factors were also perceived to be causative, including airborne pollution (28%), smoking (23%), and air conditioning (31%). Symptoms perceived to be caused by an infection were associated with a higher degree of suffering (mean degree of suffering for bacteria/virus and common cold/influenza; 3.4 and 3.0, respectively). Medicinal products were used for all perceived causes, but more commonly for sore throats thought to be caused by

  1. Incidence, causes, severity and treatment of throat discomfort: a four-region online questionnaire survey

    Directory of Open Access Journals (Sweden)

    Addey Dilys

    2012-08-01

    Full Text Available Abstract Background Acute sore throat is commonly associated with viral infections. Consumers typically rely on over-the-counter treatments and other remedies to treat symptoms; however, limited information is available regarding consumer perceptions of sore throat or treatment needs. The aim of this study was to investigate perceptions of throat discomfort and how these influence attitudes and consumer behaviour with regard to treatment. Methods Online consumer surveys were completed by participants invited by email between 2003 and 2004 in four markets: the UK, France, Poland, and Malaysia. The questionnaire consisted of 24 questions that covered key issues surrounding throat discomfort including incidence in the past 12 months, causes, severity, effects on functionality and quality of life, actions taken to relieve throat discomfort, the efficacy of these approaches and the reasons behind using specific products. Results In total, 6465 men and women aged ≥18 years were surveyed, identifying 3514 participants who had suffered throat discomfort/irritation in the past 12 months (response rate of 54%. These participants completed the full survey. The breakdown of throat discomfort sufferers was: UK, 912; France, 899; Poland, 871; Malaysia, 832. A high proportion of respondents experienced one or more instances of throat discomfort in the previous 12 months, with an overall incidence of 54%. Infections including the common cold/influenza and other bacteria/viruses were commonly perceived causes of throat discomfort (72% and 46%, respectively. Physical and environmental factors were also perceived to be causative, including airborne pollution (28%, smoking (23%, and air conditioning (31%. Symptoms perceived to be caused by an infection were associated with a higher degree of suffering (mean degree of suffering for bacteria/virus and common cold/influenza; 3.4 and 3.0, respectively. Medicinal products were used for all perceived causes, but more

  2. A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

    Science.gov (United States)

    Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, Dorte Launholt; Jensen, Peter Kjestrup Axel

    2014-08-01

    We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. © 2014 Wiley Periodicals, Inc.

  3. First report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) causing severe disease in Allomyrina dichotoma in Korea.

    Science.gov (United States)

    Lee, Seokhyun; Park, Kwan-Ho; Nam, Sung-Hee; Kwak, Kyu-Won; Choi, Ji-Young

    2015-01-01

    Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is used as a biological control to reduce the pest population. Here, we report for the first time that the OrNV may have landed on Korea and may be the major pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After peroral inoculation, over 60% of infected larvae perished in 6 wk. This viral disease spreads very fast in several locations throughout Korea. This threat not only makes economic loss of local farms rearing A. dichotoma larvae but also may disturb the ecosystem by transmitting to wild A. dichotoma. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

  4. Evidence of increasing drought severity caused by temperature rise in southern Europe

    International Nuclear Information System (INIS)

    Vicente-Serrano, Sergio M; Lopez-Moreno, Juan-I; Lorenzo-Lacruz, Jorge; García-Ruiz, José M; Azorin-Molina, Cesar; Morán-Tejeda, Enrique; Revuelto, Jesús; Beguería, Santiago; Sanchez-Lorenzo, Arturo; Trigo, Ricardo; Coelho, Fatima; Espejo, Francisco

    2014-01-01

    We use high quality climate data from ground meteorological stations in the Iberian Peninsula (IP) and robust drought indices to confirm that drought severity has increased in the past five decades, as a consequence of greater atmospheric evaporative demand resulting from temperature rise. Increased drought severity is independent of the model used to quantify the reference evapotranspiration. We have also focused on drought impacts to drought-sensitive systems, such as river discharge, by analyzing streamflow data for 287 rivers in the IP, and found that hydrological drought frequency and severity have also increased in the past five decades in natural, regulated and highly regulated basins. Recent positive trend in the atmospheric water demand has had a direct influence on the temporal evolution of streamflows, clearly identified during the warm season, in which higher evapotranspiration rates are recorded. This pattern of increase in evaporative demand and greater drought severity is probably applicable to other semiarid regions of the world, including other Mediterranean areas, the Sahel, southern Australia and South Africa, and can be expected to increasingly compromise water supplies and cause political, social and economic tensions among regions in the near future. (paper)

  5. Clinical profile of high-risk febrile neutropenia in a tertiary care hospital

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    Mohan V Bhojaraja

    2016-06-01

    Full Text Available Background Infection in the immunocompromised host has been a reason of concern in the clinical setting and a topic of debate for decades. In this study, the aim was to analyse the clinical profile of high-risk febrile neutropenic patients. Aims To study the clinical profile of high risk febrile neutropenia patients with the objective of identifying the most common associated malignancy, most common associated pathogen, the source of infection, to correlate the treatment and management with that of the Infectious Diseases Society of America (IDSA 2010 guidelines and to assess the clinical outcome. Methods A cross-sectional time bound study was carried out and a total of 80 episodes of high-risk febrile neutropenia were recorded among patients with malignancies from September 2011 to July 2013 with each episode being taken as a new case. Results Non-Hodgkin’s lymphoma (30 per cent was the most common malignancy associated, commonest source of infection was due to central venous catheters, the commonest pathogens were gram negative (52 per cent the treatment and management of each episode of high risk febrile neutropenia correlated with that of IDSA 2010 guidelines and the mortality rate was 13.75 per cent. Conclusion Febrile neutropenia is one of the major complications and cause of mortality in patients with malignancy and hence understanding its entire spectrum can help us reduce morbidity and mortality.

  6. Impalement of an unusual foreign body on the temporomandibular joint causing severe trismus.

    Science.gov (United States)

    Ito, Ryohei; Kubota, Kosei; Furudate, Ken; Nakagawa, Hiroshi; Kon, Takao; Tamura, Yoshihiro; Kobayashi, Wataru

    2016-12-01

    A penetrating injury by a foreign body is comparatively common in the oral and maxillofacial region. On the other hand, injury to the temporomandibular joint (TMJ) by a foreign object is very rare. The TMJ is an anatomically narrow space surrounded by hard bony processes. An unusual case of trauma with severe trismus caused by a foreign body that impaled the TMJ is reported. A 55-year-old man presented with a 5 × 1-cm laceration to the right cheek caused by a flying object propelled during the use of a lawn mower. The edge of the foreign body had a metallic wire, which became imbedded in the wound. His jaw opening was severely limited. Computed tomography revealed that the foreign body was 3 mm in diameter and was impaled on the articular capsule. The object was successfully removed, and the wound and interior of the TMJ were irrigated. Rehabilitation of mouth opening was started on postoperative day 3. On day 9, mouth opening had improved to 35 mm, and he was discharged. After 1 year, mouth opening was 45 mm with no sign of any TMJ disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Gender-Based Violence Causing Severe Multiple Injuries; a Case Report

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    Adalard Falschung

    2018-04-01

    Full Text Available Introduction: Gender-based violence (GBV against women has been identified as a global health and development issue. We reported a case of GBV causing sever, multiple injuries in a middle-aged female. Case report: A 47-year-old woman presented to emergency room with disturbed level of consciousness, shortness of breath and multiple patches of skin discoloration. On examination, the patient was semi-conscious, with multiple ecchymosis and bilateral decreased air entry. Computed tomography scan of the neck and chest showed six rib fractures on the left side, and eight rib fractures on the right side, sternal fracture, manubriosternal dislocation, bilateral hemothorax, fracture of body of eleventh thoracic vertebra, and fracture of cervical spine of fifth and seventh vertebrae. The patient was intubated and admitted to intensive care unit. She was discharged with good health condition after 23 days of hospital admission. Conclusion: GBV is still a cause of severe trauma that puts the patient’s life at risk.

  8. Starvation Ketoacidosis: A Cause of Severe Anion Gap Metabolic Acidosis in Pregnancy

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    Nupur Sinha

    2014-01-01

    Full Text Available Pregnancy is a diabetogenic state characterized by relative insulin resistance, enhanced lipolysis, elevated free fatty acids and increased ketogenesis. In this setting, short period of starvation can precipitate ketoacidosis. This sequence of events is recognized as “accelerated starvation.” Metabolic acidosis during pregnancy may have adverse impact on fetal neural development including impaired intelligence and fetal demise. Short periods of starvation during pregnancy may present as severe anion gap metabolic acidosis (AGMA. We present a 41-year-old female in her 32nd week of pregnancy, admitted with severe AGMA with pH 7.16, anion gap 31, and bicarbonate of 5 mg/dL with normal lactate levels. She was intubated and accepted to medical intensive care unit. Urine and serum acetone were positive. Evaluation for all causes of AGMA was negative. The diagnosis of starvation ketoacidosis was established in absence of other causes of AGMA. Intravenous fluids, dextrose, thiamine, and folic acid were administered with resolution of acidosis, early extubation, and subsequent normal delivery of a healthy baby at full term. Rapid reversal of acidosis and favorable outcome are achieved with early administration of dextrose containing fluids.

  9. Severe Neonatal Hyperbilirubinemia; Causes and Contributing Factors Leading to Exchange Transfusion at Ghaem Hospital in Mashhad

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    Farhad Heydarian

    2010-12-01

    Full Text Available Hyperbilirubinemia is common in neonates; it can have a serious rising course. Due to its critical morbidity called "kernicterus", severe neonatal hyperbilirubinemia causes which lead to exchange transfusion, should be clarified. This descriptive cross sectional study performed with reviewing of files of 118 neonates weighting 2kg and more who had exchange transfusion in pediatrics ward at Ghaem training hospital in Mashhad from April 2004 to March 2007. Among 118 patients, 75 (63.6% were male, and 43 patients (36.4% were female. The most common cause of exchange transfusion was ABO incompatibility (38.1%. In order of frequency, unknown etiology (25.4%, Rh incompatibility (16.1% with no immune hydrops, Sepsis(8.5%, urinary tract infection (5.1% and others (3.4% (Including Crigler-Najjar and cephalohematoma were next ones. Vaginal delivery and exclusive breast feeding were detected as associated factors. Mean serum bilirubin levels was 28.7 mg/dl (SD. 9.2 ABO incompatibility. ABO incompatibility was the main cause of exchange transfusion. Male gender, vaginal delivery and exclusive breast feeding were seen more among patients who need to be exchanged. So in case of ABO incompatibility especially when delivery route is vaginal, newborns should be visited soon again after early discharge from hospital.

  10. Trends in the incidence and causes of severe visual impairment and blindness in children from Israel.

    Science.gov (United States)

    Mezer, Eedy; Chetrit, Angela; Kalter-Leibovici, Ofra; Kinori, Michael; Ben-Zion, Itay; Wygnanski-Jaffe, Tamara

    2015-06-01

    To describe trends in the incidence and causes of legal childhood blindness in Israel, one of the few countries worldwide that maintain a national registry of the blind. We performed a historical cohort study of annual reports of the National Registry of the Blind (NRB) between 1999 and 2013. All data regarding demographic information, year of registration and cause of blindness of children 0-18 years of age registered for blind certification were obtained from the annual reports of the NRB. Causes of legal blindness analyzed were optic atrophy, retinitis pigmentosa, retinopathy of prematurity (ROP), albinism, other retinal disorders, cataract, and glaucoma. The main outcome measure was the incidence of new cases of certified legal blindness. The incidence of newly registered legally blind children in Israel almost halved from 7.7 per 100,000 in 1999 to 3.1 per 100,000 in 2013. The decline was mainly attributable to a decreased incidence of blindness resulting from retinitis pigmentosa and ROP. The incidence of registered cases due to cerebral visual impairment increased. During the past decade the incidence of severe childhood visual impairment and blindness declined in Israel. A continuous decline in consanguineous marriages among the Jewish and Arab populations in Israel may have contributed to the decrease in the rate of vision loss due to retinitis pigmentosa in children. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  11. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China 230032 (China); Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Zhang, Zhuo; Shi, Xianglin [Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.

  12. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

    International Nuclear Information System (INIS)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-01-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.

  13. Severe ionosphere disturbances caused by the sudden response of evening subequatorial ionospheres to geomagnetic storms

    International Nuclear Information System (INIS)

    Tanaka, T.

    1981-01-01

    By monitoring C band beacon signals from geostationary satellites in Japan, we have observed anomalously strong ionospheric scintillations several times during three years from 1978 to 1980. These severe scinitillations occur associated with geomagnetic storms and accompany sudden and intense ionospheric perturbations in the low-latiude region. Through the analysis of these phenomena we have identified a new type of ionospheric disturbances characterized by intensifications of equatorial anomalies and successive severe ionospheric scintillations that extend to the C band range. The events occur only during a limited local time interval after the sunset, when storm time decreases of midlatitude geomagnetic fields in the same meridan take place during the same time interval. From the viewpoint of ionospheric storms, these disturbances precede the occurrence of midlatitude negative phases and storm time depressions of equatorial anomalies to indicate that the cause of the events is different from distrubed thermospheric circulations. The timing and magnitude of substorms at high-latitudes not always correlate with the events. We have concluded that the phenomena are closely related with penetrations toward low-latitudes of electric fields owing to the partial closure of asymmetrical ring currents

  14. Are patients with severe epistaxis caused by hereditary hemorrhagic telangiectasia satisfied with nostril closure surgery?

    Science.gov (United States)

    Ichimura, Keiichi; Kikuchi, Hisashi; Imayoshi, Shoichiro; Yamauchi, Tomohiko; Ishikawa, Kotaro

    2012-02-01

    Recurrent epistaxis as a manifestation of hereditary hemorrhagic telangiectasia (HHT) is usually difficult to control. Although no treatment is regarded to be completely efficacious, nostril closure is considered a modality of choice for the most severe cases. The cessation of airflow resulting from this procedure can stop bleeding by minimizing risk factors. However, loss of nasal functions is a disadvantage of nostril closure. We conducted a questionnaire survey of patients who underwent nostril closure surgery, regarding the effects and disadvantages of the operation. Seven patients were asked questions on issues including frequency and severity of epistaxis pre- and post-operatively, satisfaction of treatment, and impairment in daily living activities. Most patients reported complete cessation of bleeding. Some still had bleeding, but the frequency and severity were far lower. No transfusions were required in any of the cases. Patients reported some disadvantages, for example, respiratory, olfactory, and phonatory issues. Six out of seven patients were very satisfied with the outcome of surgery. Nostril closure surgery can remarkably reduce frequency and volume of epistaxis. Our survey indicated that satisfactory results were achieved. However, difficulties caused by complete nasal obstruction varied. Thus, individualized coping strategies are required. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Natural Disasters under the Form of Severe Storms in Europe: the Cause-Effect Analysis

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    Virginia Câmpeanu

    2009-07-01

    Full Text Available For more than 100 years, from 1900 to 2008, there were almost 400 storms natural disasters in Europe, 40% of which occurred in the 1990s. The international prognoses for the world weather suggest a tendency toward increasing in frequency and intensity of the severe storms as the climate warms. In these circumstances, for a researcher in the field of Environmental Economics, a natural question occurs, on whether people can contribute to reducing the frequency and the magnitude of severe storms that produce disastreous social and economic effects, by acting on their causes. In researching an answer to support the public policies in the field, a cause-effect analysis applied to Europe might make a contribution to the literature in the field. This especially considering the fact that international literature regarding the factors influencing global warming contains certainties in regard to the natural factors of influence, but declared incertitudes or skepticism in regard to anthropogenic ones. Skepticism, and even tension arised during the international negotiations in Copenhagen (December 2009 in regard to the agreement for limiting global warming, with doubts being raised about the methods used by experts of the International Climate Experts Group (GIEC, and thus the results obtained, which served as a basis for the negotiations. The object of critics was in regard to the form, and at times in regard to the content. It was not about contesting the phenomenon of Global warming during the negotiations, but the methods of calculation. The methodology relies on qualitative (type top down and quantitative (type correlations bottom up cause-effect analysis of the storm disasters in Europe. Based on the instruments used, we proposed a dynamic model of association of the evolution of storm disasters in Europe with anthropogenic factors, with 3 variants. Results: The diagram cause-effect (Ishikawa or fishbone diagram and quantitative correlation of sub

  16. Prevalence, phenotype and inheritance of benign neutropenia in Arabs

    Directory of Open Access Journals (Sweden)

    Nagelkerke Nicollas

    2009-03-01

    Full Text Available Abstract Background Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC 9cells/L is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. Methods ANCs were studied prospectively amongst a healthy indigenous population (n = 1032 from the United Arab Emirates undergoing a nation-wide sickle-cell and thalassemia screening program. The mean neutrophil count and the prevalence of benign neutropenia were compared by age, sex and amongst various tribes. Results The mean neutrophil count (× 109cells/L was 3.3 (range 0.95–7.6. Benign neutropenia was present in 110 (10.7% subjects of whom 24 (2.3% individuals had moderate neutropenia (ANC 0.5 – 1.0 × 109 cells/L. In the 22 tribe-family groups, the prevalence of benign neutropenia varied between 0% and 38%. Benign neutropenia showed no difference in the frequency amongst the sexes (p = 0.23 and it was independent of age (Spearman's rho = 0.05, p = 0.13. The age-related mean neutrophil count was the lowest in Arabs when compared with other ethnic groups (Blacks, Europeans and Mexicans. The inheritance of benign neutropenia was consistent with an autosomal dominant pattern; however, the diversity of observed phenotypes suggested the presence of more than one genetic variant for this trait. Conclusion Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait.

  17. Staphylococcus aureus seroproteomes discriminate ruminant isolates causing mild or severe mastitis

    Directory of Open Access Journals (Sweden)

    Le Maréchal Caroline

    2011-02-01

    Full Text Available Abstract Staphylococcus aureus is a major cause of mastitis in ruminants. In ewe mastitis, symptoms range from subclinical to gangrenous mastitis. S. aureus factors or host-factors contributing to the different outcomes are not completely elucidated. In this study, experimental mastitis was induced on primiparous ewes using two S. aureus strains, isolated from gangrenous (strain O11 or subclinical (strain O46 mastitis. Strains induced drastically distinct clinical symptoms when tested in ewe and mice experimental mastitis. Notably, they reproduced mild (O46 or severe (O11 mastitis in ewes. Ewe sera were used to identify staphylococcal immunoreactive proteins commonly or differentially produced during infections of variable severity and to define core and accessory seroproteomes. Such SERological Proteome Analysis (SERPA allowed the identification of 89 immunoreactive proteins, of which only 52 (58.4% were previously identified as immunogenic proteins in other staphylococcal infections. Among the 89 proteins identified, 74 appear to constitute the core seroproteome. Among the 15 remaining proteins defining the accessory seroproteome, 12 were specific for strain O11, 3 were specific for O46. Distribution of one protein specific for each mastitis severity was investigated in ten other strains isolated from subclinical or clinical mastitis. We report here for the first time the identification of staphylococcal immunogenic proteins common or specific to S. aureus strains responsible for mild or severe mastitis. These findings open avenues in S. aureus mastitis studies as some of these proteins, expressed in vivo, are likely to account for the success of S. aureus as a pathogen of the ruminant mammary gland.

  18. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

    NARCIS (Netherlands)

    Aapro, M.S.; Bohlius, J.; Cameron, D.A.; Dal Lago, L.; Donnelly, J.P.; Kearney, N.; Lyman, G.H.; Pettengell, R.; Tjan-Heijnen, V.C.; Walewski, J.; Weber, D.C.; Zielinski, C.

    2011-01-01

    Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or

  19. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours.

    NARCIS (Netherlands)

    Aapro, M.S.; Cameron, D.; Pettengell, R.; Bohlius, J.; Crawford, J.; Ellis, M.; Kearney, N.; Lyman, G.H.; Tjan-Heijnen, V.C.; Walewski, J.A.; Weber, D.C.; Zielinski, C.

    2006-01-01

    Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose

  20. Types and severity of operated supraclavicular brachial plexus injuries caused by traffic accidents.

    Science.gov (United States)

    Kaiser, Radek; Waldauf, Petr; Haninec, Pavel

    2012-07-01

    Brachial plexus injuries occur in up to 5% of polytrauma cases involving motorcycle accidents and in approximately 4% of severe winter sports injuries. One of the criteria for a successful operative therapy is the type of lesion. Upper plexus palsy has the best prognosis, whereas lower plexus palsy is surgically untreatable. The aim of this study was to evaluate a group of patients with brachial plexus injury caused by traffic accidents, categorize the injuries according to type of accident, and look for correlations between type of palsy (injury) and specific accidents. A total of 441 brachial plexus reconstruction patients from our department were evaluated retrospectively(1993 to 2011). Sex, age, neurological status, and the type and cause of injury were recorded for each case. Patients with BPI caused by a traffic accident were assessed in detail. Traffic accidents were the cause of brachial plexus injury in most cases (80.7%). The most common type of injury was avulsion of upper root(s) (45.7%) followed by rupture (28.2%), complete avulsion (16.9%) and avulsion of lower root(s) (9.2%). Of the patients, 73.9% had an upper,22.7% had a complete and only 3.4% had a lower brachial plexus palsy. The main cause was motorcycle accidents(63.2%) followed by car accidents (23.5%), bicycle accidents(10.7%) and pedestrian collisions (3.1%) (paccidents had a higher percentage of lower avulsion (22.7%) and a lower percentage of upper avulsion (29.3%), whereas cyclists had a higher percentage of upper avulsion (68.6%) based on the data from the entire group of patients (paccidents (9.3%,paccidents),significantly more upper and fewer lower palsies were present. In the bicycle accident group, upper palsy was the most common (89%). Study results indicate that the most common injury was an upper plexus palsy. It was characteristic of bicycle accidents, and significantly more common in car and motorcycle accidents. The results also indicate that it is important to consider the

  1. Agricultural measures to reduce radiation doses to man caused by severe nuclear accidents

    International Nuclear Information System (INIS)

    Dorp, F. van; Eleveld, R.; Frissel, M.J.

    1981-01-01

    Agricultural land and products may become contaminated after a severe nuclear accident. If radiation doses to man caused by the ingestion of contaminated agricultural products from such areas will be unacceptably high, measures to reduce this radiation dose will have to be taken. Radiation doses to man can be estimated by using models which describe quantitatively the transfer of radionuclides through the biosphere. The following processes and pathways are described in this study: accidental releases into atmospheric environments and subsequent nearby deposition; contamination of crops by direct deposition and the subsequent short term pathway (e.g. grass-cow-milk-man); contamination of soil and the subsequent long term pathway (e.g. soil-crop-man, soil-grass-cattle-milk/meat-man). Depending on the degree of contamination and on the estimated radiation doses to man, various measures are advised. (Auth.)

  2. Severe Toxic Skin Reaction Caused by a Common Anemone and Identification of the Culprit Organism.

    Science.gov (United States)

    Tezcan, Özgür Deniz; Gözer, Özgür

    2015-01-01

    In a marine envenomation, identification of the culprit organism can be difficult. In this case report, we present our method to identify snakelocks anemone (Anemonia viridis or formerly Anemonia sulcata) as the culprit of a severe toxic skin reaction. A. viridis is one of the most common anemones of the Mediterranean Sea and the North Atlantic Ocean. It lives at a depth of up to 10 m. It is a member of the phylum Cnidaria, which includes jellyfish, anemones, hydroids, and corals. They have toxic organelles called cnidocysts that have the capacity to inject venom with microscopic harpoon-like structures. The cnidocysts of A. viridis may cause toxic and allergic reactions, and although its venom is one of the most studied cnidarian venoms, detailed case reports are rare. © 2015 International Society of Travel Medicine.

  3. Depletion of WRN protein causes RACK1 to activate several protein kinase C isoforms

    DEFF Research Database (Denmark)

    Massip, L; Garand, C; Labbé, A

    2010-01-01

    show that a knock down of the WRN protein in normal human fibroblasts induces phosphorylation and activation of several protein kinase C (PKC) enzymes. Using a tandem affinity purification strategy, we found that WRN physically and functionally interacts with receptor for activated C-kinase 1 (RACK1......), a highly conserved anchoring protein involved in various biological processes, such as cell growth and proliferation. RACK1 binds strongly to the RQC domain of WRN and weakly to its acidic repeat region. Purified RACK1 has no impact on the helicase activity of WRN, but selectively inhibits WRN exonuclease...... activity in vitro. Interestingly, knocking down RACK1 increased the cellular frequency of DNA breaks. Depletion of the WRN protein in return caused a fraction of nuclear RACK1 to translocate out of the nucleus to bind and activate PKCdelta and PKCbetaII in the membrane fraction of cells. In contrast...

  4. Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent hyponatremia caused by adrenal insufficiency

    Directory of Open Access Journals (Sweden)

    Kyung Mi Jang

    2017-09-01

    Full Text Available Pituitary stalk interruption syndrome (PSIS involves the occurrence of a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. Diagnosis is confirmed using magnetic resonance imaging. Patients with PSIS have a variable degree of pituitary hormone deficiency and a wide spectrum of clinical manifestations. The clinical course of the disease in our patient is similar to that of a syndrome of inappropriate antidiuretic hormone secretion. This is thought to be caused by failure in the suppression of vasopressin secretion due to hypocortisolism. To the best of our knowledge, there is no case report of a patient with PSIS presenting with hyponatremia as the first symptom in Korean children. Herein, we report a patient with PSIS presenting severe recurrent hyponatremia as the first symptom, during adolescence and explain the pathophysiology of hyponatremia with secondary adrenal insufficiency.

  5. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    Science.gov (United States)

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.

  6. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  7. Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy.

    Science.gov (United States)

    Broekaert, Ilse Julia; Becker, Kerstin; Gottschalk, Ingo; Körber, Friederike; Dötsch, Jörg; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Hünseler, Christoph; Cirak, Sebahattin

    2018-04-16

    Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature. We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein ( PLVAP ) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. A SEVERE CASE OF ACUTE NECROTIC PANCREATITIS CAUSED BY DUODENAL CYST DUPLICATION

    Directory of Open Access Journals (Sweden)

    Gabriel Constantinescu

    2018-03-01

    Full Text Available Introduction. Duodenal duplication cyst (DDC is a rare congenital malformation that appears in the embryonic development of the digestive tract. It is a benign condition usually diagnosed in infancy and early childhood, being a rare and difficult diagnosis in adult population. DDC is a recognized cause of duodenal obstruction, acute pancreatitis, obstructive jaundice and even digestive hemorrhage. Case presentation. We report the case of a young adult male with abdominal pain history, who presents with recurrent episodes of acute severe necrotic pancreatitis. The abdominal computed tomography scan revealed a Balthazar C necrotic pancreatitis with partial thrombosis of the splenic vein and a cystic mass in the second part of the duodenum. The endoscopic ultrasonography (EUS established that the duodenal cystic lesion came from the second layer, meaning the submucosa. We performed endoscopic cystotomy with complete evacuation of the fluid content into the duodenum, with favorable clinical outcome. Conclusions. The particularity of the case is represented by the low incidence of this pathology and the rare form of presentation, meaning acute pancreatitis probably from pancreatic ductular hypertension caused by the DDC.

  9. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues

    Science.gov (United States)

    Faber, James E.; Zhang, Hua; Lassance-Soares, Roberta M.; Prabhakar, Pranay; Najafi, Amir H.; Burnett, Mary Susan; Epstein, Stephen E.

    2011-01-01

    Objective Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals, and their remodeling in 3-, 16-, 24-, and 31-months-old mice. Methods and Results Aging caused an “age-dose-dependent” greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T-cells or macrophages to remodeling collaterals. However, eNOS signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated eNOS and VASP in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (e.g., 6- and 3-fold, respectively, in 24-months-old mice) after artery occlusion. This was not associated with rarefaction of similarly-sized arterioles. Collateral remodeling was also reduced. Conclusions Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury. PMID:21617137

  10. Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

    Science.gov (United States)

    Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

    2015-10-01

    In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Severe burn injuries caused by bioethanol-design fireplaces-an overview on recreational fire threats.

    Science.gov (United States)

    Kraemer, Robert; Knobloch, Karsten; Lorenzen, Johan; Breuing, Karl H; Koennecker, Soeren; Rennekampff, Hans-Oliver; Vogt, Peter M

    2011-01-01

    Commercially available bioethanol-fueled fireplaces have become increasingly popular additions for interior home decoration in Europe and more recently in the United States. These fireplaces are advertised as smokeless, ecologically friendly, and do not require professional installation, formal gas lines, or venting. Although manufacturers and businesses promote their safety, recent presentations of injuries have alerted the authors to the relevant danger bioethanol fireplaces can pose for the incautious user. Are bioethanol fireplaces going to become the future threat in domestic burn accidents beside common barbeque burns? A Medline literature search on barbeque and domestic fireplace accidents was performed to compare and stratify the injury patterns reported and to identify a risk profile for contemporary bioethanol-fueled fireplaces. To exemplify, two representative clinical cases of severe burn accidents caused by bioethanol-fueled fireplaces, both treated in the burn unit of the authors, are being presented. Design fireplaces are being recognized as an increasing source of fuel and fire-related danger in the home. This risk may be underestimated by the uninformed customer, resulting in severe burn injuries. Because bioethanol-fueled fireplaces have become more commonplace, they may overtake barbecue-related injury as the most common domestic burn injury.

  12. Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

    Science.gov (United States)

    Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi

    Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- - SEA ) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - - SEA deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α 0 -thal carrier.

  13. Rationalizing the approach to children with fever in neutropenia

    NARCIS (Netherlands)

    Ammann, Roland A.; Tissing, Wim J. E.; Phillips, Bob

    Purpose of review Fever in neutropenia is the most frequent potentially life-threatening complication of chemotherapy in children and adolescents with cancer. This review summarizes recent studies that refine our knowledge of how to manage pediatric fever in neutropenia, and their implications for

  14. New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim

    Directory of Open Access Journals (Sweden)

    Ghidini M

    2016-06-01

    Full Text Available Michele Ghidini,1 Jens Claus Hahne,2 Francesco Trevisani,3 Stefano Panni,1 Margherita Ratti,1 Laura Toppo,1 Gianluca Tomasello1 1Medical Department, Division of Oncology, ASST di Cremona, Ospedale di Cremona, Cremona, Italy; 2Division of Molecular Pathology, The Institute of Cancer Research, London and Sutton, UK; 3Department of Urology, Unit of Urology/Division of Oncology, IRCCS Ospedale San Raffaele, URI, Milan, Italy Abstract: Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2 and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim’s efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the

  15. Velvet bean severe mosaic virus: a distinct begomovirus species causing severe mosaic in Mucuna pruriens (L.) DC.

    Science.gov (United States)

    Zaim, Mohammad; Kumar, Yogesh; Hallan, Vipin; Zaidi, A A

    2011-08-01

    Velvet bean [Mucuna pruriens (L.) DC] is one of the most important medicinal plants. It is used to treat many ailments, but is widely used for the treatment especially for Parkinson's disease because of the presence of 3,4-dihydroxyphenylalanine (L-dopa) in it. It was noticed in last 5 years that the plants in the field showed severe mosaic, downward curling of the leaves, stunting, etc. This is consistently observed over the years in India. The disease was transmitted by whiteflies and by grafting and the causal agent was found to be a bipartite begomovirus. The whole genome was amplified by rolling circle amplification (RCA) using ϕ-29 DNA polymerase and characterized. DNA-A and DNA-B shared a 124-nucleotide (nt) long highly conserved (98%) common region (CR). Comparisons with other begomovirus showed that DNA-A sequence has highest identity (76%) with an isolate of Mungbean yellow mosaic India virus (MYMIV; AY937195) reported from India. This data suggested that the present isolate is a new species of genus Begomovirus for which the name "Velvet bean severe mosaic virus" (VbSMV) is proposed. DNA-B has a maximum sequence identity of 49% with an isolate of Horsegram yellow mosaic virus (HgYMV; AM932426) reported from India. Infectious clones consisting of a 1.7 mer partial tandem repeat of DNA-A and a dimer of DNB-B were constructed and agro-inoculated to Macuna pruriens (L.) DC plants, which showed field observed symptoms 24 days post-infiltration (dpi). In phylogenetic analysis, DNA-A and DNA-B of the present isolate grouped with DNA-A of different begomoviruses reported from fabaceous crops. The study presents first ever molecular evidence of any disease in velvet bean and whole genome analysis of the causative virus which is a distinct bipartite species of Begomovirus.

  16. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy.

    Science.gov (United States)

    Rosas-Vargas, H; Bahi-Buisson, N; Philippe, C; Nectoux, J; Girard, B; N'Guyen Morel, M A; Gitiaux, C; Lazaro, L; Odent, S; Jonveaux, P; Chelly, J; Bienvenu, T

    2008-03-01

    Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.

  17. Brd2 disruption in mice causes severe obesity without Type 2 diabetes.

    Science.gov (United States)

    Wang, Fangnian; Liu, Hongsheng; Blanton, Wanda P; Belkina, Anna; Lebrasseur, Nathan K; Denis, Gerald V

    2009-12-14

    Certain human subpopulations are metabolically healthy but obese, or metabolically obese but normal weight; such mutations uncouple obesity from glucose intolerance, revealing pathways implicated in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin. In the present study, we show that wholebody disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue, heat production and expression of mitochondrial uncoupling proteins in brown adipose tissue, reduced macrophage infiltration in white adipose tissue, and lowered blood glucose, leading to an improved metabolic profile and avoiding eventual Type 2 diabetes. Brd2 is highly expressed in pancreatic beta-cells, where it normally inhibits beta-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, Brd2 normally co-represses PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and inhibits adipogenesis. Brd2 knockdown protects 3T3-L1 adipocytes from TNF-alpha (tumour necrosis factor-alpha)-induced insulin resistance, thereby decoupling inflammation from insulin resistance. Thus hypomorphic Brd2 shifts energy balance toward storage without causing glucose intolerance and may provide a novel model for obese metabolically healthy humans.

  18. Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities

    Directory of Open Access Journals (Sweden)

    Moore Kelley

    2004-05-01

    Full Text Available Abstract Background Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can disrupt patients' routines and activities. Methods We surveyed patients to assess how clinic visits for treatment with chemotherapy and the management of neutropenia affect their time and activities. Results The mean amounts of time affected by these visits ranged from approximately 109 hours (hospitalization for neutropenia and 8 hours (physician and chemotherapy to less than 3 hours (laboratory and treatment with filgrastim or pegfilgrastim. The visits for filgrastim or pegfilgrastim were comparable in length, but treatment with filgrastim requires several visits per chemotherapy cycle and treatment with pegfilgrastim requires only 1 visit. Conclusions This study provides useful information for future modelling of additional factors such as disease status and chemotherapy schedule and provides information that should be considered in managing chemotherapy-induced neutropenia.

  19. Severe complications caused by dissolution of latex with consequent self-disintegration of esophageal plastic tubes.

    Science.gov (United States)

    Löser, C

    2000-09-01

    A case of decisive material degeneration of an esophageal Celestin tube is described: a 50-year-old man with adenocarcinoma of the distal esophagus received a Celestin tube for palliative endoscopic treatment and 8 months later presented with suddenly occurring complete dysphagia. Dissolution of the latex layer in the proximal as well as the distal part of the tube had caused self-disintegration of the Celestin tube and had liberated the monofilament nylon coil which completely obstructed the lumen of the tube. Endoscopic tube removal was only possible by careful attachment of a balloon catheter and peroral extraction after insufflation with contrast medium up to 5 atm. A Medline-based review of the literature revealed different but predominantly severe complications (perforation, hemorrhage, obstruction, and peritonitis) based on material fatigue of the latex layer in esophageal Celestin tubes. At least 6 months after placement of a Celestin tube, regular fluoroscopic controls should be performed to detect early disintegration of the tube. Indication for the placement of Celestin tubes in patients with benign esophageal strictures and longer life expectancy should be assessed very critically.

  20. An unusual cause of severe dyspnea: A laryngeal live leech: Case report.

    Science.gov (United States)

    Anajar, Said; Ansari, Rachid; Hassnaoui, Jawad; Abada, Reda; Roubal, Mohammed; Mahtar, Mohammed

    2017-01-01

    Foreign bodies in the upper airways are one of the most challenging otolaryngology emergencies, leeches present a very rare cause of airway foreign bodies around the world. A 6-year-old girl was referred to our otolaryngology department at a tertiary university hospital with a severe dyspnea and hemoptysis. Nasofibroscopy revealed a dark living leech in the supraglottic area which extends to the glottis. The patient was urgently admitted to the operating room, the leech was grasped and removed with a foreign body forceps with a full length of more than 6cm. All symptoms were relieved post operatively and she was discharged one day later. Leeches should be suspected as an airway foreign body in patients with a recent history of drinking from stream water. Prevention remains the best treatment for such cases based simply on hygiene measures like not drinking stream water directly and filtering drinking water before it is used. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Did Eucalyptus contribute to environment degradation? Implications from a dispute on causes of severe drought in Yunnan and Guizhou, China

    OpenAIRE

    WenJun Zhang

    2012-01-01

    Various viewpoints were proposed to explain the causes of recent years' severe drought occurred in Yunnan and Guizhou, China. In general there are two parties of viewpoints, the Eucalyptus cause and climate change cause. I think Yunnan-Guizhou drought has been mainly caused by abnormal climate change. Eucalyptus was not significant in the formation of Yunnan-Guizhou drought. However, the forestation effect of Eucalyptus in China was not good. Environment quality and biodiversity in Eucalyptus...

  2. Molecular Epidemiology of Epidemic Severe Malaria Caused by Plasmodium vivax in the State of Amazonas, Brazil

    National Research Council Canada - National Science Library

    Santos-Ciminera, Patricia D

    2005-01-01

    .... In Manaus, the capital of Amazonas, atypical cases of Plasmodium vivax infections, including patients presenting with severe thrombocytopenia and bleeding, led to the hypothesis that severe disease...

  3. Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Guy, Stephen D.; Tramontana, Adrian R. [Western Health, Department of Infectious Diseases, Private Bag, Footscray, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia); Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Infectious Diseases, Melbourne, Victoria (Australia); Lau, Eddie; Hicks, Rodney J. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, Victoria (Australia); Seymour, John F. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Haematology, Melbourne, Victoria (Australia)

    2012-08-15

    Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [{sup 18} F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature {>=}38 C and neutrophil count <500 cells/{mu}l for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/{mu}l (range 0-730 cells/{mu}l). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

  4. Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

    International Nuclear Information System (INIS)

    Guy, Stephen D.; Tramontana, Adrian R.; Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A.; Lau, Eddie; Hicks, Rodney J.; Seymour, John F.

    2012-01-01

    Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [ 18 F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38 C and neutrophil count <500 cells/μl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/μl (range 0-730 cells/μl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

  5. Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases

    OpenAIRE

    Weycker Derek; Sofrygin Oleg; Seefeld Kim; Deeter Robert G; Legg Jason; Edelsberg John

    2013-01-01

    Abstract Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classifie...

  6. Mortality caused by intracranial bleeding in non-severe hemophilia A patients

    NARCIS (Netherlands)

    Loomans, Janneke I.; Eckhardt, Corien L.; Reitter-Pfoertner, Sylvia E.; Holmstrom, Mats; Van Gorkom, B. Laros; Leebeek, F. W. G.; Santoro, C.; Haya, Saturnino; Meijer, K.; Nijziel, M. R.; Van Der Bom, J. G.; Fijnvandraat, K.

    Background: Non-severe hemophilia (factor VIII concentration [FVIII: C] of 2-40 IU dL(-1)) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on

  7. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    Science.gov (United States)

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  8. [Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis].

    Science.gov (United States)

    Ma, H X; He, L; Cai, S W; Xin, X L; Shi, H D; Zhou, L; Shi, X J

    2017-05-01

    Objective: To investigate the characteristics of spectrum and drug resistance of pathogens causing sepsis in patients with severe acute pancreatitis(SAP). Methods: The clinical data of 63 SAP patients with sepsis admitted in Department of Hepatobiliary, People's Liberation Army General Hospital from January 2014 to December 2015 were retrospectively studied. There were 47 males and 16 females, aged from 22 to 73 years, with an average age of (52±11)years. Samples were collected mainly from: (1)pancreatic and peripancreatic necrosis and abdominal drainage; (2)bile; (3) blood or deep venous catheter; (4) sputum and tracheal catheter and thoracic drainage; (5) urine. Strain identification and drug-resistance test were preformed on positive specimens. Results: Of 244 pathogenic isolates, mainly derived from abdominal cavity(36.0%), blood stream (14.0%), central venous catheter(11.8%), necrotic tissue(9.1%) and sputum(8.1%); 154(63.1%) were gram-negative bacteria, 68 cases(27.9%) were gram-positive bacteria and 22 cases(9.0%) were fungi respectively. The top six common pathogens isolated were E . coli(16.0%), E .faecium and faecalis(15.2%), P .aeruginosa(10.7%), K .pneumonia(9.8%), Acinetobacter baumanni(8.2%), Stenotrophomonas maltophilia(5.3%)respectively. The detection rate of E . coli and K . pneumonia extended-spectrum β-lactamases(ESBL) was 84.6%(33/39) and 70.8%(17/24), the resistance rate to imipeniem was 12.8% and 25.0%, to cefperazone-sulbactam was 28.2% and 29.2%. As to P . aeruginosa and Acinetobacter bacillus, the resistance rate to imipeniem was 50.0% and 75.0%, to cefperazone-sulbactam was 42.3% and 70.0%; Stenotrophomonas maltophilia was completely resistant to cefperazone-sulbactam, but sensitive to minocycline, SMZ-TMP with the resistance rate less than 40.0%. Gram-positive bacterium strains mainly included E . faecium(38.2%, 26/68), E .faecalis(16.2%, 11/68) and Staphylococcus(35.3%, 24/68) which maintained high sensitivity to vancomycin

  9. Desynchronizations in bee-plant interactions cause severe fitness losses in solitary bees.

    Science.gov (United States)

    Schenk, Mariela; Krauss, Jochen; Holzschuh, Andrea

    2018-01-01

    Global warming can disrupt mutualistic interactions between solitary bees and plants when increasing temperature differentially changes the timing of interacting partners. One possible scenario is for insect phenology to advance more rapidly than plant phenology. However, empirical evidence for fitness consequences due to temporal mismatches is lacking for pollinators and it remains unknown if bees have developed strategies to mitigate fitness losses following temporal mismatches. We tested the effect of temporal mismatches on the fitness of three spring-emerging solitary bee species, including one pollen specialist. Using flight cages, we simulated (i) a perfect synchronization (from a bee perspective): bees and flowers occur simultaneously, (ii) a mismatch of 3 days and (iii) a mismatch of 6 days, with bees occurring earlier than flowers in the latter two cases. A mismatch of 6 days caused severe fitness losses in all three bee species, as few bees survived without flowers. Females showed strongly reduced activity and reproductive output compared to synchronized bees. Fitness consequences of a 3-day mismatch were species-specific. Both the early-spring species Osmia cornuta and the mid-spring species Osmia bicornis produced the same number of brood cells after a mismatch of 3 days as under perfect synchronization. However, O. cornuta decreased the number of female offspring, whereas O. bicornis spread the brood cells over fewer nests, which may increase offspring mortality, e.g. due to parasitoids. The late-spring specialist Osmia brevicornis produced fewer brood cells even after a mismatch of 3 days. Additionally, our results suggest that fitness losses after temporal mismatches are higher during warm than cold springs, as the naturally occurring temperature variability revealed that warm temperatures during starvation decreased the survival rate of O. bicornis. We conclude that short temporal mismatches can cause clear fitness losses in solitary bees

  10. Mutations of CDKL5 Cause a Severe Neurodevelopmental Disorder with Infantile Spasms and Mental Retardation

    Science.gov (United States)

    Weaving, Linda S.; Christodoulou, John; Williamson, Sarah L.; Friend, Kathie L.; McKenzie, Olivia L. D.; Archer, Hayley; Evans, Julie; Clarke, Angus; Pelka, Gregory J.; Tam, Patrick P. L.; Watson, Catherine; Lahooti, Hooshang; Ellaway, Carolyn J.; Bennetts, Bruce; Leonard, Helen; Gécz, Jozef

    2004-01-01

    Rett syndrome (RTT) is a severe neurodevelopmental disorder caused, in most classic cases, by mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2). A large degree of phenotypic variation has been observed in patients with RTT, both those with and without MECP2 mutations. We describe a family consisting of a proband with a phenotype that showed considerable overlap with that of RTT, her identical twin sister with autistic disorder and mild-to-moderate intellectual disability, and a brother with profound intellectual disability and seizures. No pathogenic MECP2 mutations were found in this family, and the Xq28 region that contains the MECP2 gene was not shared by the affected siblings. Three other candidate regions were identified by microsatellite mapping, including 10.3 Mb at Xp22.31-pter between Xpter and DXS1135, 19.7 Mb at Xp22.12-p22.11 between DXS1135 and DXS1214, and 16.4 Mb at Xq21.33 between DXS1196 and DXS1191. The ARX and CDKL5 genes, both of which are located within the Xp22 region, were sequenced in the affected family members, and a deletion of nucleotide 183 of the coding sequence (c.183delT) was identified in CDKL5 in the affected family members. In a screen of 44 RTT cases, a single splice-site mutation, IVS13-1G→A, was identified in a girl with a severe phenotype overlapping RTT. In the mouse brain, Cdkl5 expression overlaps—but is not identical to—that of Mecp2, and its expression is unaffected by the loss of Mecp2. These findings confirm CDKL5 as another locus associated with epilepsy and X-linked mental retardation. These results also suggest that mutations in CDKL5 can lead to a clinical phenotype that overlaps RTT. However, it remains to be determined whether CDKL5 mutations are more prevalent in specific clinical subgroups of RTT or in other clinical presentations. PMID:15492925

  11. Is there still an indication for nursing patients with prolonged neutropenia in protective isolation? An evidence-based nursing and medical study of 4 years experience for nursing patients with neutropenia without isolation

    NARCIS (Netherlands)

    Mank, Arno; van der Lelie, Hans

    2003-01-01

    Patients with severe neutropenia due to high-dose chemotherapy and/or total-body irradiation are at risk of serious infections and are frequently nursed in strict protective isolation. This is a costly procedure and results in a psychological burden for the patient and its significance has been

  12. Indirect causes of severe adverse maternal outcomes: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

    Science.gov (United States)

    Lumbiganon, P; Laopaiboon, M; Intarut, N; Vogel, J P; Souza, J P; Gülmezoglu, A M; Mori, R

    2014-03-01

    To assess the proportion of severe maternal outcomes resulting from indirect causes, and to determine pregnancy outcomes of women with indirect causes. Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health. A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East. A total of 314 623 pregnant women admitted to the participating facilities. We identified the percentage of women with severe maternal outcomes arising from indirect causes. We evaluated the risk of severe maternal and perinatal outcomes in women with, versus without, underlying indirect causes, using adjusted odds ratios and 95% confidence intervals, by a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities. Severe maternal outcomes and preterm birth, fetal mortality, early neonatal mortality, perinatal mortality, low birthweight, and neonatal intensive care unit admission. Amongst 314 623 included women, 2822 were reported to suffer from severe maternal outcomes, out of which 20.9% (589/2822; 95% CI 20.1-21.6%) were associated with indirect causes. The most common indirect cause was anaemia (50%). Women with underlying indirect causes showed significantly higher risk of obstetric complications (adjusted odds ratio, aOR, 7.0; 95% CI 6.6-7.4), severe maternal outcomes (aOR 27.9; 95% CI 24.7-31.6), and perinatal mortality (aOR 3.8; 95% CI 3.5-4.1). Indirect causes were responsible for about one-fifth of severe maternal outcomes. Women with underlying indirect causes had significantly increased risks of severe maternal and perinatal outcomes. © 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

  13. Injury Severity and Causes of Death from Operation Iraqi Freedom and Operation Enduring Freedom: 2003-2004 Versus 2006

    National Research Council Canada - National Science Library

    Kelly, Joseph F; Ritenour, Amber E; McLaughlin, Daniel F; Bagg, Karen A; Apodaca, Amy N; Mallak, Craig T; Pearse, Lisa; Lawnick, Mary M; Champion, Howard R; Wade, Charles E

    2008-01-01

    .... The authors hypothesized that the severity of wounds has increased over time. In this study, they examined cause of death looking for opportunities to improve clinical research and training for the battlefield...

  14. Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine

    Directory of Open Access Journals (Sweden)

    Pravesh Sharma

    2016-01-01

    Full Text Available This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient’s psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient’s laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner.

  15. Bee moth (Galleria mellonella) allergic reactions are caused by several thermolabile antigens.

    Science.gov (United States)

    Villalta, D; Martelli, P; Mistrello, G; Roncarolo, D; Zanoni, D

    2004-09-01

    Exposure and contact with bee moth (Galleria mellonella) larvae (Gm) can cause an allergic reaction both in anglers and breeders. We described the case of an amateur fisherman who experienced an allergic reaction using Gm but not using heat-treated Gm (h-Gm) (mummies). The aim of this study was to demonstrate by immunoblotting and radioallergosorbent test (RAST)-inhibition experiments the loss of allergenic epitopes in h-Gm extracts. Galleria mellonella larvae and h-Gm were homogenized and extracted at 10% (w/v) in 0.5 M phosphate-buffered saline, pH 7.4 containing 0.5% NaN(3) for 16 h at 4 degrees C. Gm and h-Gm extracts were electrophoresed in a 10% polyacrylamide precast Nupage Bis-Tris gel at 180 mA for 1 h and the resolved proteins stained with 0.1% Coomassie brilliant blue and the molecular weight calculated. For the immunoblotting detection of allergenic components the resolved extracts were transferred onto a nitrocellulose membrane and incubated with the patient's serum. Bound specific-IgE was detected by peroxidase-conjugated anti-human IgE. RAST inhibition experiments were performed according to the Ceska method. The protein profile of Gm and h-Gm extracts resulted markedly different in number, intensity and the position of bands, indicating that heat-treatment modifies the chemical-physical characteristics of the protein contents. The Gm extract showed a strong-coloured band at 73 kDa and more than 20 components ranging from 12 to 133 kDa; h-Gm showed two main band at 77 and 38 kDa and about 15 faint bands between 20 and 133 kDa apparently without any correspondence to the bands present in the Gm extract. Immunoblotting with the patient's serum demonstrated several bands of reactivity with the Gm extract ranging from 20 to 100 kDa and no recognizable bands, but only a diffuse smear with h-Gm. When used in a RAST inhibition experiment the h-Gm extract demonstrated an inability to compete with the Gm one for the binding to patient's IgE serum. The h

  16. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

    NARCIS (Netherlands)

    Gennery, A.R.; Slatter, M.A.; Rice, J.; Hoefsloot, L.H.; Barge, D.; McLean-Tooke, A.; Montgomery, T.; Goodship, J.A.; Burt, A.D.; Flood, T.J.; Abinun, M.; Cant, A.J.; Johnson, D.

    2008-01-01

    More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are

  17. Oral features of a family with benign familial neutropenia.

    Science.gov (United States)

    Porter, S R; Luker, J; Scully, C; Oakhill, A

    1994-05-01

    The oral features of three members of a family with familial benign neutropenia (a mother and two children) are detailed. Prepubertal periodontitis, oral ulceration, and angular stomatitis were the principal features.

  18. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

    Science.gov (United States)

    Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

    2013-01-31

    Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

  19. Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis sicca caused by Sjogren syndrome - A uniocular evaluation

    NARCIS (Netherlands)

    Mansour, Khaled; Leonhardt, Carolien J.; Kalk, Wouter W.; Bootsma, Hendrika; Bruin, Klaas J.; Blanksma, Lieuwe J.

    Purpose: A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjogren syndrome. Methods: Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe

  20. Relating fire-caused change in forest structure to remotely sensed estimates of fire severity

    Science.gov (United States)

    Jamie M. Lydersen; Brandon M. Collins; Jay D. Miller; Danny L. Fry; Scott L. Stephens

    2016-01-01

    Fire severity maps are an important tool for understanding fire effects on a landscape. The relative differenced normalized burn ratio (RdNBR) is a commonly used severity index in California forests, and is typically divided into four categories: unchanged, low, moderate, and high. RdNBR is often calculated twice--from images collected the year of the fire (initial...

  1. Different clinical features of anaphylaxis according to cause and risk factors for severe reactions

    Directory of Open Access Journals (Sweden)

    Sang-Yoon Kim

    2018-01-01

    Conclusions: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention.

  2. Trends and causes of severity, size, and number of fires in northwestern California, USA.

    Science.gov (United States)

    Miller, J D; Skinner, C N; Safford, H D; Knapp, E E; Ramirez, C M

    2012-01-01

    Research in the last several years has indicated that fire size and frequency are on the rise in western U.S. forests. Although fire size and frequency are important, they do not necessarily scale with ecosystem effects of fire, as different ecosystems have different ecological and evolutionary relationships with fire. Our study assessed trends and patterns in fire size and frequency from 1910 to 2008 (all fires > 40 ha), and the percentage of high-severity in fires from 1987 to 2008 (all fires > 400 ha) on the four national forests of northwestern California. During 1910-2008, mean and maximum fire size and total annual area burned increased, but we found no temporal trend in the percentage of high-severity fire during 1987-2008. The time series of severity data was strongly influenced by four years with region-wide lightning events that burned huge areas at primarily low-moderate severity. Regional fire rotation reached a high of 974 years in 1984 and fell to 95 years by 2008. The percentage of high-severity fire in conifer-dominated forests was generally higher in areas dominated by smaller-diameter trees than in areas with larger-diameter trees. For Douglas-fir forests, the percentage of high-severity fire did not differ significantly between areas that re-burned and areas that only burned once (10% vs. 9%) when re-burned within 30 years. Percentage of high-severity fire decreased to 5% when intervals between first and second fires were > 30 years. In contrast, in both mixed-conifer and fir/high-elevation conifer forests, the percentage of high-severity fire was less when re-burned within 30 years compared to first-time burned (12% vs. 16% for mixed conifer; 11% vs. 19% for fir/high-elevation conifer). Additionally, the percentage of high-severity fire did not differ whether the re-burn interval was less than or greater than 30 years. Years with larger fires and greatest area burned were produced by region-wide lightning events, and characterized by less winter

  3. A Novel Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohidrotic Ectodermal Dysplasia

    DEFF Research Database (Denmark)

    Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, D. L.

    2014-01-01

    We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous......-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. (C) 2014 Wiley Periodicals, Inc....

  4. Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations.

    Science.gov (United States)

    Chahin, Abdullah; Opal, Steven M

    2017-03-01

    Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L pneumophila pneumonia from other respiratory pathogens. L pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Massive hookworm infection as a cause of intestinal bleeding and severe anemia].

    Science.gov (United States)

    Nair, Gayatri V; Cazorla, Ernesto; Choque, Henry; White, A Clinton; Cabada, Miguel M

    2016-01-01

    Overt gastrointestinal bleeding caused by hookworm infection is rarely reported. We present a 34 year old male with lower gastrointestinal bleeding with evidence of massive hookworm infection on colonoscopy and discuss the need to consider hookworm infection as a possible etiology of gastrointestinal bleed in endemic areas.

  6. Tratamiento ambulatorio del paciente con neutropenia febril Outpatient therapy in patients with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Andrés Londoño Gallo

    2008-01-01

    Full Text Available

    El tratamiento de los pacientes con neoplasia y neutropenia febril plantea muchas dudas. Una de ellas, que genera ansiedad en el personal de la salud, el paciente y sus familiares, es la necesidad de hospitalización porque ésta implica exponer a gérmenes intrahospitalarios potencialmente resistentes a un paciente cuyo sistema inmune puede no estar en las mejores condiciones; incluso con un aislamiento óptimo existe el riesgo de adquirir una infección nosocomial. Muchos estudios han tratado de validar métodos para clasificar a los pacientes con fiebre y neutropenia en grupos de diferente riesgo, como fundamento para implementar estrategias de tratamiento selectivo; así se ha abierto la posibilidad de utilizar medidas más conservadoras para el tratamiento de los episodios de bajo riesgo, entre ellas la administración de regímenes orales ambulatorios de antibióticos de amplio espectro; ello sin demeritar la necesidad de aplicar un juicio clínico adecuado, hacer un buen seguimiento y tener acceso a la atención médica inmediata. La neutropenia es una de las consecuencias graves de la quimioterapia para el cáncer, y se ha demostrado que el tratamiento del paciente neutropénico febril con antibióticos intravenosos reduce la mortalidad. La terapia oral podría ser una alternativa aceptable para pacientes bien seleccionados. Ella puede mejorar la calidad de vida de los pacientes con cáncer, evitar las complicaciones asociadas con la terapia intravenosa y disminuir los costos del tratamiento.

    Treatment of patients with neoplasia and febrile neutropenia, as a consequence of chemotherapy, poses many doubts, among them the need for hospitalization, since this implies exposure to potentially resistant nosocomial microorganisms. Even under the best isolation techniques, there may

  7. Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

    Directory of Open Access Journals (Sweden)

    Hae Rim Kim

    2013-12-01

    Full Text Available Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

  8. Water hammer caused by rapid steam production in a severe accident in a light water reactor

    International Nuclear Information System (INIS)

    Inasaka, Fujio; Adachi, Masaki; Murata, Hiroyuki; Aya, Izuo

    2007-01-01

    We conducted the experimental studies on the water hammer caused by striking of a water mass pushed up by a rapidly growing steam bubble, using a cylindrical model containment vessel of 0.4286 m in diameter. In the experiments, a rapid gas growth was simulated by injecting high-pressure steam into a water pool. It was clarified that coherency of the water mass movement and its water hammer caused by the condensable gas production considerably decreased in comparison with the case of the non-condensable gas production because the rising velocity of the water mass was suppressed due to the steam bubble condensation. On the basis of the data, experimental correlations for estimating the water hammer on the structures in the containment vessel were proposed. (author)

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

    Directory of Open Access Journals (Sweden)

    Milačić Nena

    2015-07-01

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

  10. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    OpenAIRE

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, ...

  11. Frequency, severity and causes of unexpected allergic reactions to food: A systematic literature review

    NARCIS (Netherlands)

    Versluis, A.; Knulst, A.C.; Kruizinga, A.G.; Michelsen, A.; Houben, G.F.; Baumert, J.L.; Os-Medendorp, H. van

    2015-01-01

    Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

  12. Teachers' Assumptions Regarding the Severity, Causes, and Outcomes of Behavioral Problems in Preschoolers: Implications for Referral.

    Science.gov (United States)

    Walker, Elaine; And Others

    1984-01-01

    Asked preschool teachers (N=100) to rate severity, long-term outcome, stability, and importance of constitutional and environmental determinants for case vignettes describing three syndromes: aggression, hyperactivity, and withdrawal, and to judge the need for referral. Results indicated little evidence of sex bias in teachers' evaluations of the…

  13. Frequency, severity and causes of unexpected allergic reactions to food : A systematic literature review

    NARCIS (Netherlands)

    Versluis, A.; Knulst, A. C.; Kruizinga, A. G.; Michelsen, A.; Houben, G. F.; Baumert, J. L.; van Os-Medendorp, H.

    2015-01-01

    Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

  14. Trends and causes of severity, size, and number of fires in northwestern California, USA

    Science.gov (United States)

    J. D. Miller; Carl Skinner; H. D. Safford; Eric E. Knapp; C. M. Ramirez

    2012-01-01

    Research in the last several years has indicated that fire size and frequency are on the rise in western U.S. forests. Although fire size and frequency are important, they do not necessarily scale with ecosystem effects of fire, as different ecosystems have different ecological and evolutionary relationships with fire. Our study assessed trends and patterns in fire...

  15. Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

    Science.gov (United States)

    Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

    2018-01-01

    A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

  16. Contesting the Cause and Severity of the Black Death: A Review Essay

    OpenAIRE

    Noymer, A.

    2007-01-01

    The essay is a book review of Ole J. Benedictow's "The Black Death, 1346-1353: The Complete History". It discusses the history, demography, and epidemiology of the Black Death, an epidemic that struck fourteenth-century Europe with a severity that has not be equaled by any other epidemic in recorded history, before or since.

  17. Severe pain as a possible cause of dropped head syndrome that was attenuated after amputation of an ischemic lower limb.

    Science.gov (United States)

    Maki, Satoshi; Koda, Masao; Furuya, Takeo; Takahashi, Kazuhisa; Yamazaki, Masashi

    2016-03-02

    Dropped head syndrome (DHS) is defined as weakness of the neck extensor muscles causing a correctable chin-on-the-chest deformity. Here we report the case of a patient with severe pain from lower leg ischemia showing DHS whose symptoms were attenuated by pain relief after amputation of the severely ischemic lower leg. To our knowledge this is the first report indicating that severe pain can cause DHS. A 64-year-old Asian woman was referred to our department with a 1-month history of DHS. She also suffered from severe right foot pain because of limb ischemia. She began to complain of DHS as her gangrenous foot pain worsened. She had neck pain and difficulty with forward gaze. We found no clinical or laboratory findings of neuromuscular disorder or isolated neck extensor myopathy. We amputated her leg below the knee because of progressive foot gangrene. Her severe foot pain resolved after the surgery and her DHS was attenuated. Severe pain can cause DHS. If a patient with DHS has severe pain in another part of the body, we recommend considering aggressive pain relief as a treatment option.

  18. A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery

    Directory of Open Access Journals (Sweden)

    Nicola C. Frenkel

    2017-01-01

    Full Text Available Brunner’s gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner’s glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner’s glands without signs of malignancy.

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

    LENUS (Irish Health Repository)

    Fogarty, H

    2018-05-01

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

  20. X-ray analysis of 80 patients with severe endemic fluorosis caused by coal burning

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.P.; Yuan, M.B.; Liu, G.F. [Luzhou Medical College, Luzhou (China)

    1996-05-01

    Radiographs of 80 patients with severe endemic fluorosis of coalburning type (CBFF) - 49 males and 31 females aged 30 to 70 years - were analysed to examine the changes to the bone substance, peripheral structure of bone, and joints. The changes to bone substance were: (1) osteosclerosis type, 62 cases (77.5%); (2) mixed type, 16 cases (21.25%); (3) osteoporosis type, one case (1.25%); (4) osteomalacia type, one case (1.25%). The changes to the joints were found in the hips and elbows in 79 cases (98.75%), and in the knees in 75 cases (93.75%). When combinations of the above three changes occur, the classification of the disease is according to the most severe one of the three. Our findings can increase the accuracy of X-ray diagnosis, making it more consistent with clinical diagnosis, thus improving prevention and treatment of CBEF.

  1. Severe Acute Infection Due to Serratia marcescens Causing Respiratory Distress in An Immunocompetent Adult.

    Science.gov (United States)

    Ruiz-Sada, Pablo; Escalante, Mikel; Lizarralde, Eva

    2016-01-01

    The role of Serratia marcescens changed from a harmless saprophytic microorganism to an important opportunistic human pathogen. It often causes nosocomial device-associated outbreaks and rarely serious invasive community acquired infections. We present a case of a community-acquired Serratia marcescens bacteremia leading to Respiratory Distress Syndrome in a previously healthy 51-year-old man without identifiable risk factors. Full recovery was achieved with solely medical treatment and observation in ICU during three days. To our knowledge it is an extremely uncommon presentation and just few cases have been previously reported in the literature.

  2. Mitral Perivalvular Leak after Blunt Chest Trauma: A Rare Cause of Severe Subacute Mitral Regurgitation.

    Science.gov (United States)

    Marchese, Nicola; Facciorusso, Antonio; Vigna, Carlo

    2015-12-01

    Blunt chest trauma is a very rare cause of valve disorder. Moreover, mitral valve involvement is less frequent than is aortic or tricuspid valve involvement, and the clinical course is usually acute. In the present report, we describe the case of a 49-year-old man with a perivalvular mitral injury that became clinically manifest one year after a violent, nonpenetrating chest injury. This case is atypical in regard to the valve involved (isolated mitral damage), the injury type (perivalvular leak in the absence of subvalvular abnormalities), and the clinical course (interval of one year between trauma and symptoms).

  3. Pigeon fancier’s lung – An under-diagnosed cause of severely debilitating and chronic breathlessness

    Directory of Open Access Journals (Sweden)

    Vishal Chopra

    2017-07-01

    Full Text Available Pigeon fanciers lung or Bird fanciers lung (BFL is one of the common and preventable causes of hypersensitivity pneumonitis. It is an under diagnosed cause of severe incapacitating breathlessness and can be acute, sub-acute or chronic. We report a case of 53 year old female who presented with severe chronic breathlessness due to regular exposure to pigeons for last 35 years. Clinicians should take a detailed history of exposure in patients with unexplained breathlessness as the avoidance of exposure to the antigens can reverse the disease preventing the morbidity and mortality of the patient.

  4. Alkaptonuria: A rare cause of recurrent severe back pain in the emergency department

    Directory of Open Access Journals (Sweden)

    MSeidahmed

    2012-09-01

    Full Text Available We report a 45 year-old male patient who presented to the emergency department of Hamad General Hospital with recurrent severe low back pain. Clinical examination revealed characteristic deposition of blue-brownish pigment in the sclera and ear. X-ray revealed diffuse intervertebral disc calcification. Alkaptonuria was suspected and the diagnosis was confirmed by detection of high levels of homogentisic acid in the urine.

  5. Comprehensive Treatment of Severe Periodontal and Periimplant Bone Destruction Caused by Iatrogenic Factors

    Directory of Open Access Journals (Sweden)

    Gregor-Georg Zafiropoulos

    2018-01-01

    Full Text Available Dental implant success requires placement after periodontal therapy, with adequate bone volume, plaque control, primary stability, control of risk factors, and use of well-designed prostheses. This report describes the surgical and prosthetic management of a patient with severe iatrogenic periodontal/periimplant bone destruction. Methods. A 55-year-old female smoker with fixed partial dentures (FPDs supported on teeth and implants presented with oral pain, swelling, bleeding, and a 10-year history of multiple implant placements and implants/prosthesis failures/replacements. Radiographs showed severe bone loss, subgingival caries, and periapical lesions. All implants and teeth were removed except implants #4 and #10 which served to retain an interim maxillary restoration. Bone defects were covered with nonresorbable dPTFE membranes. In the mandible, three new implants were placed and loaded immediately with a bar-retained temporary denture. Results. Seven months postoperatively, the bone defects were regenerated, and three additional mandibular implants were placed. All mandibular implants were splinted and loaded with a removable overdenture. Conclusions. In this case, periimplant infection and tissue destruction resulted from the lack of periodontal treatment/maintenance and failure to use evidence-based surgical and loading protocols. Combination therapy resolved the disease and the patient's severe discomfort while providing immediate function and an aesthetic solution.

  6. A Woman with Black Beads in Her Stomach: Severe Gastric Ulceration Caused by Yttrium-90 Radioembolization

    Directory of Open Access Journals (Sweden)

    Indu S. Voruganti

    2018-01-01

    Full Text Available Radioembolization (RE is a selective internal radiation therapy (SIRT delivering targeted, high-dose, intra-arterial radiation directly to the vascular supply of liver tumors. Complications can occur due to aberrant deposition or migration of radiation microspheres into nontarget locations, including normal hepatic parenchyma, lungs, pancreas, and upper gastrointestinal (UGI tract. We report a case of gastric ulcers due to yttrium-90 (90Y seed migration to the stomach to alert clinicians to this rare cause of gastric injury. A 57-year-old woman with stage IV breast cancer with liver and lung metastases presented to the hospital with 2 months of worsening nausea and vomiting. Two months prior, she had received SIRT with 90Y microspheres without complications. Upper GI endoscopy showed diffuse gastritis and extensive antral ulceration. Biopsies revealed black, spherical foreign bodies, consistent with 90Y microspheres, documenting radiation injury. Radiation-induced UGI ulceration is caused by direct radiation injury from beta-radiation. Delay in diagnosis may be due to the nonspecificity of symptoms and temporal delay of symptom onset from SIRT, which was 2 months in our patient. Also, complaints may be attributed erroneously to adjuvant chemotherapy or widespread metastatic disease. Clinicians must consider radiation-associated toxicity in any SIRT-treated patient developing abdominal symptoms.

  7. Acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia: acute onset and complete recovery.

    Science.gov (United States)

    Tu, Guo-Wei; Song, Jie-Qiong; Ting, Simon Kang Seng; Ju, Min-Jie; He, Hong-Yu; Dong, Ji-Hong; Luo, Zhe

    2015-02-03

    Critical illness polyneuropathy and myopathy are multifaceted complications that follow severe illnesses involving the sensorimotor axons and proximal skeletal muscles. These syndromes have rarely been reported among renal transplant recipients. In this paper, we report a case of acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia. The muscle strength in the patient's extremities improved gradually after four weeks of comprehensive treatment, and his daily life activities were normal a year after being discharged.

  8. Mycoplasma ovipneumoniae - A Primary Cause of Severe Pneumonia Epizootics in the Norwegian Muskox (Ovibos moschatus) Population

    DEFF Research Database (Denmark)

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality...... heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed...

  9. [Chronic and severe anemia caused by Ancylostoma duodenale in Ecuador. Diagnosis by duodenoscopy].

    Science.gov (United States)

    Calvopiña, Manuel; Flores, Jessica; Guaman, Isabel; Lara, Gabriela; Abarca, Jeyson

    2017-10-01

    For 11 years, a 38-year-old male residing in a subtropical region of Ecuador, was repeatedly diagnosed with chronic anemia, and treated with blood transfusions in a hospital of province of Cotopaxi, Ecuador. He was transferred to Quito for severe anemia, having hemoglobin of 4 g/dL. Duodenoscopy was performed and adult nematodes, identified later as Ancylostoma duodenale, were observed. The patient was successfully treated with albendazole for five consecutive days and given blood transfusions. In the control visit at eight months, without anemia and no hookworm ova in the stool examined were found.

  10. Water hammer caused by rapid gas production in a severe accident in a light water reactor

    International Nuclear Information System (INIS)

    Inasaka, Fujio; Adachi, Masaki; Aya, Izuo; Nariai, Hideki; Shiozaki, Kohki

    2005-01-01

    We investigated the water hammer caused by striking of water mass pushed up by a rapidly growing bubble and its scale effects using two cylindrical model containment vessels of 1.0 and 0.428 m diameters. We also closely observed the movement of water mass and the growing bubble in the vessels. In these experiments, rapid bubble growth was simulated by injecting high-pressure air into a water pool. It was clarified that the water mass was pushed up without any air penetration until the water level reached a certain elevation. On the basis of all data, experimental correlations for estimating the height and striking velocity of the water mass with coherency were proposed, and the water hammer pressure for exerting large forces on the structures was quantitatively evaluated. (author)

  11. Growth restriction in gastroschisis: quantification of its severity and exploration of a placental cause

    Directory of Open Access Journals (Sweden)

    Olsen Sam

    2011-10-01

    Full Text Available Abstract Background Gastroschisis patients are commonly small for gestational age (SGA, birth weight [BW] th centile. However, the extent, symmetry and causes of that growth restriction remain controversial. Methods We compared BW, crown-heel length (LT, occipitofrontal circumference (OFC and ponderal index (PI in 179 gastroschisis cases and 895 matched controls by univariate and multiple regression. Fetal ultrasounds (N = 80 were reviewed to determine onset of growth restriction. Placental histology was examined in 31 gastroschisis patients whose placental tissue was available and in 29 controls. Results Gastroschisis cases weighed less than controls (BW = 2400 ± 502 g vs. 2750 ± 532 g, p Conclusions Marked, relatively symmetric intrauterine growth restriction is an intrinsic part of gastroschisis. It begins early in the second trimester, and is associated with placental chorangiosis.

  12. A case of severe rectal hemorrhage possibly caused by radiation recall after administration of gemcitabine

    International Nuclear Information System (INIS)

    Nishimoto, Koshiro; Akise, Yushi; Uchida, Atsushi; Miyazawa, Masaharu; Kutsuki, Shoji; Hashimoto, Subaru

    2016-01-01

    Radiation recall is an acute inflammatory reaction that can be triggered when systemic agents are administered long time after radiotherapy. Because radiotherapy is now indicated for many types of cancer, care should be taken regarding possible toxic events relating to radiotherapy in combination with radio-sensitizing agents. Gemcitabine, one such anti-cancer agent, is widely used, especially for urologic cancers. We report an intriguing case of possible radiation recall in the rectum caused by gemcitabine administration 37 years after radiation therapy. From a review of the literature, it appears that there have been no reported cases of radiation recall in the rectum with such a long interval between radiation therapy and chemotherapy. Here, we describe the case and provide a literature review. (author)

  13. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

    Science.gov (United States)

    Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

    2008-04-15

    Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

  14. Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

    Energy Technology Data Exchange (ETDEWEB)

    McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

    1996-11-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

  15. Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

    Science.gov (United States)

    Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

    2015-10-01

    Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

  16. Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Lorand-Metze Irene

    2010-05-01

    Full Text Available Abstract Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang - are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10 presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31. These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.

  17. Severe anemia caused by babesiosis in a maned wolf (Chrysocyon brachyurus).

    Science.gov (United States)

    Phair, Kristen A; Carpenter, James W; Smee, Nicole; Myers, Carl B; Pohlman, Lisa M

    2012-03-01

    An 8-yr-old, captive, spayed, female maned wolf (Chrysocyon brachyurus) developed progressive lethargy and weakness over a 24-hr period. Clinical signs included vomiting, recumbency, horizontal nystagmus, possible blindness, pale icteric mucus membranes, and port-wine colored urine. A complete blood cell count revealed severe anemia (packed cell volume [PCV], 6%) and intraerythrocytic piroplasms consistent with a Babesia species. Polymerase chain reaction testing later confirmed babesiosis. The wolf was treated with imidocarb dipropionate, antibiotics, and fluid therapy. A whole-blood transfusion from a sibling maned wolf also was performed. Despite aggressive treatment, the wolf failed to improve and was euthanized. To the authors' knowledge, this is the first documented case of babesiosis in a captive maned wolf in North America. Surveillance of infectious diseases in captive and wild maned wolf populations should be expanded to include screening for Babesia species. Tick control also should be implemented to prevent and decrease transmission of the disease to this endangered species.

  18. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

    2011-05-01

    This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Severe Pleuropulmonary Paragonimiasis Caused by Paragonimus mexicanus Treated as Tuberculosis in Ecuador.

    Science.gov (United States)

    Calvopina, Manuel; Romero-Alvarez, Daniel; Macias, Rubén; Sugiyama, Hiromu

    2017-01-11

    A 30-year-old male, from a subtropical region of Ecuador, was hospitalized with a 5-year history of persistent cough with rusty brown sputum, chest pain, and progressive dyspnea. The patient underwent thoracic surgery 3 years ago for pleural effusion and subsequently received a 9-month regimen treatment of tuberculosis. However, there was no clinical resolution and symptoms became progressively worse. A chest radiograph and computerized tomography scan showed several small nodules in both lungs. Eggs of Paragonimus spp. were observed in sputum smears, but the smears were negative for acid-fast bacilli. Molecular characterization of eggs by the internal transcribed spacer-2 regions identified them as Paragonimus mexicanus The patient was treated with praziquantel and tested negative parasitologically for 12 months. There was clinical resolution of the cough and expectoration, but dyspnea and chest pain persisted. © The American Society of Tropical Medicine and Hygiene.

  20. Hyperparathyroidism-jaw Tumor Syndrome: An Overlooked Cause of Severe Hypercalcemia.

    Science.gov (United States)

    Mathews, Joseph Wolfgang; Winchester, Rhonda; Alsaygh, Nebras; Bartlett, Anne M; Luttrell, Louis

    2016-09-01

    Ossifying fibromas of the maxillofacial bones are an uncommon form of benign neoplasm usually treated by surgical excision. Up to 30% of patients with hyperparathyroidism-jaw tumor syndrome, a rare form of multiple endocrine neoplasia resulting from autosomal dominant inactivating mutation of the Hrpt2 tumor suppressor gene, initially present with ossifying fibromas. Coincident hypercalcemia because of the presence of parathyroid adenoma is common in these patients, of whom 15% may have or may develop parathyroid carcinoma. The authors present a case of severe postsurgical hypercalcemia after removal of a large maxillary ossifying fibroma in a patient with previously unrecognized hyperparathyroidism-jaw tumor AU3 syndrome. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  1. [Severe hypercalcemia of unusual cause, looking for the culprit: Case report and review of the literature].

    Science.gov (United States)

    Jalbert, M; Mignot, A; Gauchez, A-S; Dobrokhotov, A-C; Fourcade, J

    2018-04-27

    Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found. A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia. Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D. We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule. Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  2. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes

    NARCIS (Netherlands)

    van de Pol, L.A.; Wolf, N.I.; van Weissenbruch, M.M.; Stam, C.J.; Weiss, M.M.; Waisfisz, Q.; Kevelam, S.H.; Bugiani, M.; van de Kamp, J.M.; Knaap, M.

    2015-01-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an

  3. Causes of severe visual impairment and blindness in students in schools for the blind in Northwest Ethiopia.

    Science.gov (United States)

    Asferaw, Mulusew; Woodruff, Geoffrey; Gilbert, Clare

    2017-01-01

    To determine the causes of severe visual impairment and blindness (SVI/BL) among students in schools for the blind in Northwest Ethiopia and to identify preventable and treatable causes. Students attending nine schools for the blind in Northwest Ethiopia were examined and causes assigned using the standard WHO record form for children with blindness and low vision in May and June 2015. 383 students were examined, 357 (93%) of whom were severely visually impaired or blind (blind and four were SVI, total 104. The major anatomical site of visual loss among those 0-15 years was cornea/phthisis (47.1%), usually due to measles and vitamin A deficiency, followed by whole globe (22.1%), lens (9.6%) and uvea (8.7%). Among students aged 16 years and above, corneal/phthisis (76.3%) was the major anatomical cause, followed by lens (6.3%), whole globe (4.7%), uvea (3.6%) and optic nerve (3.2%). The leading underlying aetiology among students aged blindness, mainly as the result of measles and vitamin A deficiency, is still a public health problem in Northwest Ethiopia, and this has not changed as observed in other low-income countries. More than three-fourth of causes of SVI/BL in students in schools for the blind are potentially avoidable, with measles/vitamin A deficiency and cataract being the leading causes.

  4. Morphological adjustments in a meandering reach of the middle Yangtze River caused by severe human activities

    Science.gov (United States)

    Zhou, Meirong; Xia, Junqiang; Lu, Jinyou; Deng, Shanshan; Lin, Fenfen

    2017-05-01

    In the past 50 years, the Shishou reach in the middle Yangtze River underwent significant channel evolution owing to the implementation of an artificial cutoff, the construction of bank revetment works and the operation of the Three Gorges Project (TGP). Based on the measured hydrological data and topographic data, the processes of channel evolution in this reach were investigated mainly from the adjustments in planform and cross-sectional geometries. The variation in planform geometry obtained in this study indicates that (i) the artificial cutoff at Zhongzhouzi caused the river regime to adjust drastically, with the mean rate of thalweg migration at reach scale of 42.0 m/a over the period 1966-1975; (ii) then the effect of this artificial cutoff reduced gradually, with the mean migration rate decreasing to 40 m/a owing to the occurrence of high water levels in 1993-1998; and (iii) the average annual rate of thalweg migration decreased to 29.3 m/a because of the impacts of various bank protection engineering and the TGP operation during the period 2002-2015. However, remarkable thalweg migration processes still occurred in local regions after the TGP operation, which resulted in significant bankline migration in local reaches of Beimenkou, Shijiatai, and Tiaoxiankou. In addition, the adjustments of bankfull channel geometry were investigated at section and reach scales after the TGP operation. Calculated results show that lateral channel migration in this reach was restricted by various river regulation works and that channel evolution was mainly characterized by an increase in bankfull depth and cross-sectional area. Empirical relationships were developed between the reach-scale bankfull dimensions (depth and area), the bankfull widths at specified sections, and the previous 5-year average fluvial erosion intensity during flood seasons, with high correlation degrees between them being obtained.

  5. Clonal Clusters and Virulence Factors of Group C and G Streptococcus Causing Severe Infections, Manitoba, Canada, 2012-2014.

    Science.gov (United States)

    Lother, Sylvain A; Demczuk, Walter; Martin, Irene; Mulvey, Michael; Dufault, Brenden; Lagacé-Wiens, Philippe; Keynan, Yoav

    2017-07-01

    The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012-2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.

  6. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis

    Science.gov (United States)

    Ichikawa, Shoji; Imel, Erik A.; Kreiter, Mary L.; Yu, Xijie; Mackenzie, Donald S.; Sorenson, Andrea H.; Goetz, Regina; Mohammadi, Moosa; White, Kenneth E.; Econs, Michael J.

    2007-01-01

    Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). Herein we report a homozygous missense mutation (H193R) in the KLOTHO (KL) gene of a 13-year-old girl who presented with severe tumoral calcinosis with dural and carotid artery calcifications. This patient exhibited defects in mineral ion homeostasis with marked hyperphosphatemia and hypercalcemia as well as elevated serum levels of parathyroid hormone and FGF23. Mapping of H193R mutation onto the crystal structure of myrosinase, a plant homolog of KL, revealed that this histidine residue was at the base of the deep catalytic cleft and mutation of this histidine to arginine should destabilize the putative glycosidase domain (KL1) of KL, thereby attenuating production of membrane-bound and secreted KL. Indeed, compared with wild-type KL, expression and secretion of H193R KL were markedly reduced in vitro, resulting in diminished ability of FGF23 to signal via its cognate FGF receptors. Taken together, our findings provide what we believe to be the first evidence that loss-of-function mutations in human KL impair FGF23 bioactivity, underscoring the essential role of KL in FGF23-mediated phosphate and vitamin D homeostasis in humans. PMID:17710231

  7. [Severe inflammation of the muzzle caused by a nose ring in a breeding bull].

    Science.gov (United States)

    Braun, U; Gautschi, A; Reichle, S; Gerspach, C

    2010-09-01

    This report describes the findings in a bull with severe inflammation of the muzzle and nose attributable to a nose ring. The most striking finding was that the bull continually licked the right side of the upper lip. The muzzle and right upper lip were swollen, hard, reddened and partially depigmented. Mucopurulent nasal discharge and salivation were also noted, and palpation of the right upper lip was extremely painful. Based on the findings, purulent infection of the right side of the muzzle, right naris and external nasal passage was diagnosed. After removing the nose ring the affected areas were washed daily for four days with a camomile-containing solution after which a chlorhexidine and dexpanthenol salve was applied. The bull also received ceftiofur and ketoprofen. The general condition and appetite of the bull normalised within a few days, and the inflammatory lesions resolved with the exception of the areas of depigmentation. After ten days of treatment, the bull was considered healthy and discharged from the clinic.

  8. Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

    Science.gov (United States)

    Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

    2017-08-03

    Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

    Science.gov (United States)

    Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

    2015-02-05

    Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Homozygous PMS2 deletion causes a severe colorectal cancer and multiple adenoma phenotype without extraintestinal cancer.

    Science.gov (United States)

    Will, Olivia; Carvajal-Carmona, Luis G; Gorman, Patricia; Howarth, Kimberley M; Jones, Angela M; Polanco-Echeverry, Guadalupe M; Chinaleong, Jo-Anne; Günther, Thomas; Silver, Andrew; Clark, Susan K; Tomlinson, Ian

    2007-02-01

    We report a patient of Indian descent with parental consanguinity, who developed 10 carcinomas and 35 adenomatous polyps at age 23 and duodenal adenocarcinoma at age 25. He also had dysmorphic features, mental retardation, and café-au-lait spots but no brain tumor. We aimed to establish his molecular diagnosis. Germ-line screening for APC and MYH/MUTYH mutations was normal as was immunohistochemistry for MLH1 and MSH2 proteins. Investigation by array-comparative genomic hybridization revealed deletion of a small region on chromosome 7. Using polymerase chain reaction, this region was refined to a 400-kilobase deletion, which included exons 9-15 of the PMS2 gene, and all coding regions of oncomodulin, TRIAD3, and FSCN1. The deletion was confirmed as homozygous, and both parents were carriers. Immunohistochemistry showed absent PMS2 expression in all tumors and normal tissue. Most tumors showed microsatellite instability, more marked at dinucleotide than mononucleotide repeats. The tumors harbored no somatic mutations in APC, BRAF, AXIN2, or beta-catenin, but KRAS2 and TGFBR2 mutations were found. Our patient represents a novel phenotype for homozygous PMS2 mutation and perhaps the most severe colorectal cancer phenotype-in terms of numbers of malignancies at an early age-described to date. PMS2 mutations-and perhaps other homozygous mismatch repair mutations-should be considered in any patient presenting with multiple gastrointestinal tumors, since our patient could not be distinguished clinically from cases with attenuated familial adenomatous polyposis or MUTYH-associated polyposis.

  11. Mycoplasma ovipneumoniae - A Primary Cause of Severe Pneumonia Epizootics in the Norwegian Muskox (Ovibos moschatus) Population

    Science.gov (United States)

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko; Vikøren, Turid; Ayling, Roger D.; Bergsjø, Bjarne; Sigurðardóttir, Ólöf G.; Bretten, Tord

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing) of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004–2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus) on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two species were a

  12. Laryngeal giant cell tumour presenting as a tongue base lesion causing severe dysphagia

    Directory of Open Access Journals (Sweden)

    Mohd Razi M. Saud, MBBS

    2018-04-01

    Full Text Available الملخص: أورام الخلايا العملاقة هي آفات حميدة وغير مألوفة تظهر في الحنجرة. قد يصاب المريض بصعوبة في البلع، وبحة في الصوت وتورم في الجهة الأمامية من الرقبة. أورام الخلايا العملاقة هي نادرة للغاية، وهناك حالات قليلة في الأدبيات المنشورة. نعرض لحالة إمرأة مسنة قدمت بصعوبة شديدة في البلع، وورم في قاعدة اللسان. أظهرت نتيجة الورم بأنه ورم الخلايا العملاقة في الحنجرة وتم علاجه بنجاح باستخدام المعالجة الكيميائية. Abstract: Giant cell tumours are benign lesions that are uncommonly found in the larynx. Patients with these tumours may present with dysphagia, hoarseness and anterior neck swelling. Giant cell tumours are extremely rare and only a few cases have been reported. We present a case of an elderly woman who presented with severe dysphagia and a mass at the base of her tongue. The mass was found to be a laryngeal giant cell tumour and was successfully treated with chemotherapy. الكلمات المفتاحية: أورام الخلايا العملاقة, الحنجرة, صعوبة البلع, دينوسوماب, المعالجة الكيميائية, Keywords: Chemotherapy, Denosumab, Dysphagia, Giant cell tumour, Larynx

  13. Identification of the cause of severe skin infection by Fournier transform infrared spectroscopy: a case of Fournier's gangrene caused by fish bone.

    Science.gov (United States)

    Shimizu, Takae; Harada, Kazutoshi; Akazawa, Satoshi; Yamaguchi, Miyuki; Inozume, Takashi; Kawamura, Tatsuyoshi; Shibagaki, Naotaka; Momosawa, Akira; Shimada, Shinji

    2014-06-01

    Fournier's gangrene (FG) is an infrequent but highly lethal infection. Here we report a 74-year-old man who presented with genital swelling and severe malaise. Based on the physical and imaging examination results, the diagnosis of FG was confirmed. Intraoperative findings showed dirty necrosis of soft tissue, and a splinter-shaped foreign body was found in the perirectal region. The foreign body was thought to be the cause of the condition, and it was analyzed using Fourier transform infrared spectroscopy. We found that the foreign body was a mixture of calcium phosphate and protein, suggesting that the splinter was a bone. Moreover, during the medical interview, the patient mentioned about intake of fish around the time of onset of symptoms. Therefore, to confirm the results of the analysis, DNA was extracted from the foreign body, and genomic PCR with subsequent sequence analysis was performed. The DNA sequence was identical to that of Oncorhynchus kisutch, a salmon that is a very popular food in Japan. On the basis of these findings, we concluded that FG in this case was caused by the penetration into the rectum of an accidentally ingested fish bone. Although some cases of intra-abdominal abscess due to accidental ingestion of fish bone have been reported, FG caused by fish bone is extremely rare. © 2014 Japanese Dermatological Association.

  14. Severe rickets in a young girl caused by celiac disease: the tragedy of delayed diagnosis: a case report.

    Science.gov (United States)

    Al-Sharafi, Butheinah A; Al-Imad, Shafiq A; Shamshair, Amani M; Al-Faqeeh, Derhim H

    2014-10-08

    Celiac disease is a systemic immune mediated disease which usually presents with gastrointestinal symptoms, but it may present with extra gastrointestinal manifestations such as metabolic bone disease and failure to thrive. This may lead to a delay in the diagnosis. We present a 13 year old female from the middle east with an 8 year history of severe rickets causing multiple bone deformities leaving the child crippled with bowing of both of her arms and legs. The patient was also found to have growth failure, anemia and on further workup she was found to have celiac disease. We are presenting this case because it shows a severe case of rickets after malabsorption for many years. Celiac disease should be kept in mind as a cause of rickets in patients not responding to usual forms of treatment or when associated with other manifestations of malabsorption.

  15. Research on water hammer forces caused by rapid growth of bubbles at severe accidents of water cooled reactors

    International Nuclear Information System (INIS)

    Inasaka, Fujio; Adachi, Masaki; Aya, Izuo

    2004-01-01

    At severe accidents of Water Cooled Reactors a great deal of gas is expected to be produced in a short time within the water of lower part of nuclear pressure vessel and containment vessel caused by hydrogen production with a metal water reaction and steam explosions with direct contact of melting core and water. Water hammer forces caused by rapid growth of bubbles shall work on the wall of containment vessel and affect its integrity. Coherency of water block movement is not clear, whether simultaneous or in the same direction. Water block behavior and water hammer forces caused by rapid growth of bubbles have been tested using a modified scale model and analyzed to obtain experimental correlated equation to estimate water block's rising distance and velocity from water hammer data. Numerical analysis using RELAP5-3D (Reactor Excursion and Leak Analysis Program) has been conducted to evaluate water hammer forces and makes clear its modifications needed. (T. Tanaka)

  16. Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.

    Science.gov (United States)

    Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran

    2010-03-01

    Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Severe hemolytic disease of fetus and newborn caused by red blood cell antibodies undetected at first-trimester screening (CME).

    Science.gov (United States)

    Dajak, Slavica; Stefanović, Vedran; Capkun, Vesna

    2011-07-01

    The objective was to determine clinical consequences of anti-D and non-D antibodies undetected at first-trimester screening for infant or fetus. This retrospective cohort study included all pregnant women with red blood cell (RBC) antibodies who were tested between 1993 and 2008. Data were obtained from the forms for tracking immunization at the transfusion department. Each form was analyzed for three data sets: the order of screening at which the antibodies were detected (initial or repeated screening), the order of pregnancy (first pregnancy or higher), and whether the antibodies caused severe hemolytic disease of fetus and newborn (HDFN). In D- women, anti-D was detected in 1.3% of cases. The anti-D was undetected in 72 (37%) cases on the first-trimester screening, of which eight cases were complicated by severe HDFN. In this group, three patients were primigravidae. An overall non-D incidence of 0.2% was observed. In 16 cases, non-D were undetected on the first-trimester screening (10 anti-c, two anti-E, two anti-C, one anti-S, and one case of anti-Rh17). Non-D antibodies undetected on initial screening caused 11 cases of severe HDFN (27% of all severe non-D HDFN). Ten of them were in multiparous women. Seven of 11 cases with severe HDFN that were missed were caused by anti-c. The third-trimester screening may detect RBC antibodies that were not present or detected on the first-trimester screening. Such screening may be especially relevant in D+ multiparous women due to the risk of HDFN. © 2010 American Association of Blood Banks.

  18. Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene.

    Science.gov (United States)

    de Pablos, Augusto Luque; García-Nieto, Victor; López-Menchero, Jesús C; Ramos-Trujillo, Elena; González-Acosta, Hilaria; Claverie-Martín, Félix

    2014-05-01

    Bartter syndrome Type IV is a rare subtype of the Bartter syndromes that leads to both severe renal salt wasting and sensorineural deafness. This autosomal recessive disease is caused by mutations in the gene encoding barttin, BSND, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. Patients differ in the severity of renal symptoms, which appears to depend on the modification of channel function by the mutant barttin. To date, only a few BSND mutations have been reported, most of which are missense or nonsense mutations. In this study, we report the identification of the first insertion mutation, p.W102Vfs*7, in the BSND gene of a newborn girl with acute clinical symptoms including early-onset chronic renal failure. The results support previous data indicating that mutations that are predicted to abolish barttin expression are associated with a severe phenotype and early onset renal failure.

  19. Did Eucalyptus contribute to environment degradation? Implications from a dispute on causes of severe drought in Yunnan and Guizhou, China

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2012-06-01

    Full Text Available Various viewpoints were proposed to explain the causes of recent years' severe drought occurred in Yunnan and Guizhou, China. In general there are two parties of viewpoints, the Eucalyptus cause and climate change cause. I think Yunnan-Guizhou drought has been mainly caused by abnormal climate change. Eucalyptus was not significant in the formation of Yunnan-Guizhou drought. However, the forestation effect of Eucalyptus in China was not good. Environment quality and biodiversity in Eucalyptus plantation forests has been degrading in last decades. Enhancement of alleopathy of Eucalyptus trees under drought conditions would partly contribute to biodiversity reduction and environment degradation in Eucalyptus plantation forests. For existing Eucalyptus plantation forests of Yunnan, I suggest that some improvement measures should be adopted. Artificial weeding and cleaning in Eucalyptus plantation forests should be banned. Density of Eucalyptus trees needs to be reduced. Biodiversity should be artificially improved in Eucalyptus plantation forests. In the future, the mountains and lands with better vegetation cover must not be reclaimed for Eucalyptus planting. Eucalyptus plantation forests should be made in barren mountains and lands with poor biodiversity.

  20. Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

    Directory of Open Access Journals (Sweden)

    Jillian N Pearring

    2017-04-01

    Full Text Available Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.

  1. Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

    Directory of Open Access Journals (Sweden)

    Peterson Josh F

    2006-12-01

    Full Text Available Abstract Background Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. Methods We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm3 and fever (a temperature above 38°C or 100.4°F, who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. Results Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI 31% – 50% of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8. When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5 and $18,925 (95% CI 3,289 – 34,563, respectively. Conclusion Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial.

  2. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

    NARCIS (Netherlands)

    Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

    Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in

  3. Upper gastrointestinal bleeding in severely burned patients: a case-control study to assess risk factors, causes, and outcome.

    Science.gov (United States)

    Kim, Young Jin; Koh, Dong Hee; Park, Se Woo; Park, Sun Man; Choi, Min Ho; Jang, Hyun Joo; Kae, Sea Hyub; Lee, Jin; Byun, Hyun Woo

    2014-01-01

    To determine the risk factors, causes, and outcome of clinically important upper gastrointestinal bleeding that occurs in severely burned patients. The charts of all patients admitted to the burn intensive care unit were analyzed retrospectively over a 4-year period (from January 2006 to December 2009). Cases consisted of burned patients who developed upper gastrointestinal bleeding more than 24 hours after admission to the burn intensive care unit. Controls were a set of patients, in the burn intensive care unit, without upper gastrointestinal bleeding matched with cases for age and gender. Cases and controls were compared with respect to the risk factors of upper gastrointestinal bleeding and outcomes. During the study period, clinically important upper gastrointestinal bleeding occurred in 20 patients out of all 964 patients. The most common cause of upper gastrointestinal bleeding was duodenal ulcer (11 of 20 cases, 55%). In the multivariate analysis, mechanical ventilation (p = 0.044) and coagulopathy (p = 0.035) were found to be the independent predictors of upper gastrointestinal bleeding in severely burned patients. Upper gastrointestinal hemorrhage tends to occur more frequently after having prolonged mechanical ventilation and coagulopathy.

  4. Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

    Science.gov (United States)

    Glasser, Lewis; Meloni-Ehrig, Aurelia; Joseph, Plakyil; Mendiola, Jennifer

    2006-04-01

    We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. Copyright 2006

  5. Severe extremity amputations in surviving Palestinian civilians caused by explosives fired from drones during the Gaza War.

    Science.gov (United States)

    Heszlein-Lossius, Hanne; Al-Borno, Yahya; Shaqoura, Samar; Skaik, Nashwa; Giil, Lasse Melvær; Gilbert, Mads

    2018-02-21

    During four separate Israeli military attacks on Gaza (2006, 2009, 2012, and 2014), about 4000 Palestinians were killed and more than 17 000 injured (412 killed and 1264 injured in 2006; 1383 killed and more than 5300 injured in 2009; 130 killed and 1399 injured in 2012; and 2251 killed and 11 231 injured in 2014). An unknown number of people had traumatic amputations of one or more extremities. Use of unmanned Israeli drones for surveillance and armed attacks on Gaza was evident, but exact figures on numbers of drone strikes on Gaza are not available. The aim of this study was to explore the medical consequences of strikes on Gaza with different weapons, including drones. We studied a cohort of civilians in the Gaza Strip who had one of more traumatic limb amputation during the Israeli military attacks between 2006 and 2016. The study was done at The Artificial Limb and Polio Center (ALPC) in the Gaza Strip where most patients are treated and trained after amputation. We used standardised forms and validated instruments to record date and mechanism of injury, self-assessed health, socioeconomic status, anatomical location and length of amputation, comorbidity, and the results of a detailed clinical examination. The studied cohort consisted of 254 Paletinian civilians (234 [92%] men, 20 [8%] women, and 43 [17%] children aged 18 years and younger) with traumatic amputations caused by different weapons. 216 (85%) people had amputations proximal to wrist or ankle, 131 (52%) patients had more than one major amputation or an amputation above the knee, or both, and 136 (54%) people were injured in attacks with Israeli drones, including eight (40%) of the women. The most severe amputations were caused by drone attacks (p=0·0001). Extremity injuries after drone attacks led to immediate amputation more often than with other weapons (p=0·014). Patients injured during cease-fire periods were younger than patients injured during periods of declared Israeli military

  6. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

    Directory of Open Access Journals (Sweden)

    Dussaillant Catalina

    2012-11-01

    Full Text Available Abstract Background Severe hypertriglyceridemia (HTG has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel. Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

  8. APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

    Science.gov (United States)

    Dussaillant, Catalina; Serrano, Valentina; Maiz, Alberto; Eyheramendy, Susana; Cataldo, Luis Rodrigo; Chavez, Matías; Smalley, Susan V; Fuentes, Marcela; Rigotti, Attilio; Rubio, Lorena; Lagos, Carlos F; Martinez, José Alfredo; Santos, José Luis

    2012-11-15

    Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

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

    KAUST Repository

    Lancellotti, S.

    2015-08-13

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

  10. Diabetes mellitus caused by secondary hemochromatosis after multiple blood transfusions in 2 patients with severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Hyun Jin Kim

    2017-03-01

    Full Text Available Hemochromatosis is an inherited or secondary disorder caused by excessive iron storage leading to multiple organ damage. We describe 2 patients with diabetes mellitus caused by hemochromatosis secondary to multiple blood transfusions due to severe aplastic anemia. Subject 1, who was diagnosed with severe aplastic anemia at 15 years of age, received multiple red blood cell transfusions before he underwent autologous peripheral blood stem cell transplantation (PBSCT at 22 years of age. At 21 years of age, hyperglycemia was detected with increased hemoglobin A1c and serum ferritin levels, 9.7% and 12,910 ng/mL (normal range, 20–320 ng/mL, respectively. The 24-hour urine C-peptide level was normal with negative antiglutamic acid decarboxylase antibody. Subsequently, metformin and an iron-chelating agent were administered. However, an intensive insulin regimen was necessary 2 years after the onset of diabetes. Subject 2, who was diagnosed with severe aplastic anemia at 2 years of age, received multiple blood transfusions until she underwent haploidentical PBSCT at 13 years of age. At 11 years of age, she developed diabetes mellitus with a high serum ferritin level (12,559.8 ng/mL. She is currently 18 years old and has been treated with an intensive insulin regimen and estrogen/progesterone replacement therapy because of hypogonadotropic hypogonadism. It is presumed that the loss of insulin secretory capacity and insulin resistance played a role in the pathogenesis of diabetes mellitus due to hemochromatosis in these cases.

  11. Causes of Severe Visual Impairment and Blindness: Comparative Data From Bhutanese and Laotian Schools for the Blind.

    Science.gov (United States)

    Farmer, Lachlan David Mailey; Ng, Soo Khai; Rudkin, Adam; Craig, Jamie; Wangmo, Dechen; Tsang, Hughie; Southisombath, Khamphoua; Griffiths, Andrew; Muecke, James

    2015-01-01

    To determine and compare the major causes of childhood blindness and severe visual impairment in Bhutan and Laos. Independent cross-sectional surveys. This survey consists of 2 cross-sectional observational studies. The Bhutanese component was undertaken at the National Institute for Vision Impairment, the only dedicated school for the blind in Bhutan. The Laotian study was conducted at the National Ophthalmology Centre and Vientiane School for the Blind. Children younger than age 16 were invited to participate. A detailed history and examination were performed consistent with the World Health Organization Prevention of Blindness Eye Examination Record. Of the 53 children examined in both studies, 30 were from Bhutan and 23 were from Laos. Forty percent of Bhutanese and 87.1% of Laotian children assessed were blind, with 26.7% and 4.3%, respectively, being severely visually impaired. Congenital causes of blindness were the most common, representing 45% and 43.5% of the Bhutanese and Laotian children, respectively. Anatomically, the primary site of blinding pathology differed between the cohorts. In Bhutan, the lens comprised 25%, with whole globe at 20% and retina at 15%, but in Laos, whole globe and cornea equally contributed at 30.4%, followed by retina at 17.4%. There was an observable difference in the rates of blindness/severe visual impairment due to measles, with no cases observed in the Bhutanese children but 20.7% of the total pathologies in the Laotian children attributable to congenital measles infection. Consistent with other studies, there is a high rate of blinding disease, which may be prevented, treated, or ameliorated.

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

    KAUST Repository

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

    2015-01-01

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

  13. Clinical study of columnar balloon dilatation therapy for severe dysphagia caused by upper esophageal sphincter achalasia after stroke

    Directory of Open Access Journals (Sweden)

    Wei-bo SHAO

    2017-03-01

    Full Text Available Objective To investigate the mechanism and effect of columnar balloon dilatation therapy on treating patients with severe dysphagia caused by upper esophageal sphincter (UES achalasia after stroke. Methods Sixty -four patients with severe dysphagia caused by UES achalasia after stroke were diagnosed through Video Fluoroscopic Swallowing Study (VFSS and esophageal dynamics testing. The patients were randomly divided into control group (N = 32 and treatment group (N = 32. Patients in control group were treated with routine drug treatment and routine rehabilitation training, while patients in treatment group were treated with columnar balloon dilatation therapy on the basis of routine treatment. The treatment end point was either the patient resuming an oral diet or after 4-weeks treatment. All cases were evaluated by swallowing function of VFSS, high resolution manometry (HRM and scores of the severity of dysphagia before treatment and at treatment end point. Results Compared with before treatment, UES resting pressure (P = 0.000 and residual pressure (P = 0.000 were significantly decreased, peak pressure was significantly increased (P = 0.000, duration of relaxation was prolonged (P = 0.000, and scores of the severity of dysphagia were significantly increased (P = 0.000, 0.000 in both groups after treatment. Compared with control group, UES resting pressure (P = 0.001 and residual pressure (P = 0.000 were significantly decreased, peak pressure was significantly increased (P = 0.002, duration of relaxation was prolonged (P = 0.000, and scores of the severity of dysphagia were significantly increased (P = 0.000 in treatment group after treatment. Until the treatment end point or after 4-week treatment, the total effective rate in treatment group was significantly higher than that in control group [93.75% (30/32 vs. 81.25% (26/32; χ2 = 4.010, P = 0.000]. Conclusions Columnar balloon dilatation therapy is effective for reducing the tension of upper

  14. Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Shahideh Amini

    2014-01-01

    Full Text Available The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient. About 222 episodes (82% were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001.The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05.It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection.

  15. Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

    Science.gov (United States)

    Vulto-van Silfhout, Anneke T; Rajamanickam, Shivakumar; Jensik, Philip J; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J; Raghavan, Ramya; Reardon, Sara N; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L; Huggenvik, Jodi I; McKnight, G Stanley; Rose, Gregory M; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W M; Lugtenberg, Dorien; de Vries, Petra F; Veltman, Joris A; van Bokhoven, Hans; Brunner, Han G; Rauch, Anita; de Brouwer, Arjan P M; Carvill, Gemma L; Hoischen, Alexander; Mefford, Heather C; Eichler, Evan E; Vissers, Lisenka E L M; Menten, Björn; Collard, Michael W; de Vries, Bert B A

    2014-05-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    Science.gov (United States)

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

  17. Is serum albumin an independent predictor of post chemotherapy febrile neutropenia?

    International Nuclear Information System (INIS)

    Saleem, L.; Zahid, N.A.

    2017-01-01

    Objective: To evaluate the association between serum albumin and risk of post chemotherapy febrile neutropenia. Study Design: Cross sectional study. Place and Duration of Study: Department of oncology, Liaquat National Hospital, from 1st Jan 2015 to 31st Dec 2016. Material and Method: One hundred and sixty-six biopsy proven cancer patients with Eastern cooperative oncology group (ECOG) performance status <2 and without significant co-morbidities received first cycle of chemotherapy during two years study period. Different chemotherapies with moderate to severe risk of FN were used. Patient's pre-treatment serum albumin was measured and patients followed for occurrence of FN. Association between serum albumin and post chemotherapy FN was analyzed. Results: Data of 166 patients was available for final analysis. Post chemotherapy FN was observed in 19.9% (33/166) patients. Pre-chemotherapy serum albumin level was <3.5 mg/dl in (35/166) 21.1% of patients, out of which (15/35) 42.9% developed FN. Serum albumin (p=0.0005) was highly significantly associated with a risk of FN. On analysis of other factors age, gender, body surface area (BSA) and pre-chemotherapy hemoglobin level were not significantly associated with a risk of FN while body mass index (p=0.0005) was found to be associated with risk of FN. Conclusion: Pre-chemotherapy serum albumin levels were found to be statistically significant predictor of postchemotherapy febrile neutropenia.

  18. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    Science.gov (United States)

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism

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    Dimitrios Angelis

    2015-01-01

    Full Text Available Maternal Graves’ disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves’ disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves’ disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves’ disease.

  20. Research on waterhammer caused by a rapid gas production in the severe accident of a light water reactor

    International Nuclear Information System (INIS)

    Inasaka, Fujio; Adachi, Masaki; Shiozaki, Kohki; Aya, Izuo; Nariai, Hideki

    2004-01-01

    In the severe accident of an LWR (Light Water Reactor), it is supposed that a large quantity of gas is generated in a water pool of the containment vessel due to a water-metal reaction or a steam explosion. A rapid bubble growth, if the water mass is pushed up having a coherency in time and direction in its movement, would give a severe waterhammer to the structure. In this study, we conducted experiments using two cylindrical model containment vessels with 1.0 and 0.428 m diameters, and investigated the behavior of water mass pushed up by a growing bubble and the scale effect of this phenomenon. In addition, we also closely observed the heavier of a growing bubble. In these experiments, a rapid bubble growth was simulated by injecting high-pressure air into a water pool. It was observed that the water mass was pushed up without an air penetration until the water level reached a certain elevation. On the basis of all data, experimental correlations which gave a rise distance or velocity of the water mass with coherency were proposed and the waterhammer pressure which affected the structure was quantitatively evaluated. The applicability of the existing two-phase flow numerical analysis code, RELAP5-3D to the waterhammer phenomenon caused by a rapid gas production was also verified. (author)

  1. Biosimilars in the management of neutropenia: focus on filgrastim

    Directory of Open Access Journals (Sweden)

    Caselli D

    2016-02-01

    Full Text Available Désirée Caselli,1 Simone Cesaro,2 Maurizio Aricò1 1Medical Department, Pediatric Unit, Azienda Sanitaria Provinciale Ragusa, Ragusa, 2Department of Pediatrics, Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Abstract: Advances in chemotherapy and surgery allows the majority of patients to survive cancer diseases. Yet, the price may be a proportion of patients dying of complications due to treatment-induced infectious complications, such as neutropenia. With the aim of decreasing morbidity and mortality related to infectious complications, recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia. A biosimilar is a copy of an approved original biologic medicine whose data protection has expired. The patent for filgrastim expired in Europe in 2006 and in the US in 2013. This review analyses the available evidence to be considered in order to design a strategy of use of G-CSF and its biosimilars. The clinical and safety outcomes of biosimilars are well within the range of historically reported data for originator filgrastim. This underscores the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. Biosimilars can play an important role by offering the opportunity to reduce costs, thus contributing to the financial sustainability of treatment programs. Keywords: neutropenia, filgrastim, biosimilars, G-CSF, fever, prophylaxis

  2. Poikiloderma with Neutropenia in Morocco: a Report of Four Cases.

    Science.gov (United States)

    Aglaguel, Ayoub; Abdelghaffar, Houria; Ailal, Fatima; Habti, Norddine; Hesse, Sebastian; Kohistani, Naschla; Klein, Christoph; Bousfiha, Ahmed Aziz

    2017-05-01

    Poikiloderma with Neutropenia (PN) is inherited genodermatosis which results from a biallelic mutation in the USB1 gene (U Six Biogenesis 1). PN, first described in Navajo Native Americans, is characterized by early onset poikiloderma, pachyonychia, palmo-plantar hyperkeratosis, and permanent neutropenia. This condition results in frequent respiratory tract infections during infancy and childhood. From 2011 to 2013, four cases of PN were diagnosed in Morocco. In this paper, we report the first four cases of PN diagnosed in Morocco, out of three unrelated consanguinous families. We investigated the genetic, immunological, and clinical features of four Moroccan patients with PN from three unrelated consanguinous families. Mean age at onset was 3 months and mean age at diagnosis was 7.5 years. The diagnosis of these PN patients was made based on clinical features and confirmed by molecular analysis for three cases. We identified two undescribed homozygous mutations in the USB1 gene: c.609 + 1G>A in two siblings and c.518 T>G(p.(Leu173Arg)) in the other case. This report confirms the clinical and genetic identity of Poikiloderma with Neutropenia syndrome.

  3. Left ventricular global longitudinal strain is predictive of all-cause mortality independent of aortic stenosis severity and ejection fraction.

    Science.gov (United States)

    Ng, Arnold C T; Prihadi, Edgard A; Antoni, M Louisa; Bertini, Matteo; Ewe, See Hooi; Ajmone Marsan, Nina; Leung, Dominic Y; Delgado, Victoria; Bax, Jeroen J

    2017-07-28

    Left ventricular (LV) global longitudinal strain (GLS) may identify subclinical myocardial dysfunction in patients with aortic stenosis (AS). The aims of the present retrospective single centre study were to determine the independent prognostic value of LV GLS over LV ejection fraction (EF) and the role of LV GLS to further risk stratify severe AS patients before aortic valve replacement. A total of 688 patients (median age 72 years, 61.2% men) with mild (n = 130), moderate (n = 264) and severe AS (n = 294) were included. LV GLS was determined by 2D speckle tracking echocardiography. A total of 114 (16.6%) patients died before surgery during the study. When patients with severe AS and normal LVEF were dichotomized based on the median LV GLS value (-14.0%), patients with normal LVEF and 'preserved' LV GLS of ≤ -14% had significantly higher survival than patients with 'impaired' LV GLS of > -14%. There was no difference in survival between patients with normal LVEF but 'impaired' LV GLS ( > -14%) and patients with impaired LVEF (log-rank P = 0.34). LV GLS was independently associated with all-cause mortality on multivariable Cox regression analysis (hazard ratio 1.17, 95% confidence interval 1.09-1.26; P optimal timing of aortic valve replacement. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  4. Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

    Directory of Open Access Journals (Sweden)

    Paola Villafuerte-Gutierrez

    2014-01-01

    Full Text Available Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.

  5. [Nordic accident classification system used in the Danish National Hospital Registration System to register causes of severe traumatic brain injury].

    Science.gov (United States)

    Engberg, Aase Worsaa; Penninga, Elisabeth Irene; Teasdale, Thomas William

    2007-11-05

    The purpose was to illustrate the use of the accident classification system worked out by the Nordic Medico-Statistical Committee (NOMESCO). In particular, registration of causes of severe traumatic brain injury according to the system as part of the Danish National Hospital Registration System was studied. The study comprised 117 patients with very severe traumatic brain injury (TBI) admitted to the Brain Injury Unit of the University Hospital in Hvidovre, Copenhagen, from 1 October 2000 to 30 September 2002. Prospective NOMESCO coding at discharge was compared to independent retrospective coding based on hospital records, and to coding from other wards in the Danish National Hospital Registration System. Furthermore, sets of codes in the Danish National Hospital Registration System for consecutive admissions after a particular accident were compared. Identical results of prospective and independent retrospective coding were found for 65% of 588 single codes, and complete sets of codes for the same accident were identical only in 28% of cases. Sets of codes for the first admission in a hospital course corresponded to retrospective coding at the end of the course in only 17% of cases. Accident code sets from different wards, based on the same injury, were identical in only 7% of cases. Prospective coding by the NOMESCO accident classification system proved problematic, both with regard to correctness and completeness. The system--although logical--seems too complicated compared to the resources invested in the coding. The results of this investigation stress the need for better management and for better instruction to those who carry out the registration.

  6. An outbreak of severe infections among Australian infants caused by a novel recombinant strain of human parechovirus type 3.

    Science.gov (United States)

    Nelson, Tiffanie M; Vuillermin, Peter; Hodge, Jason; Druce, Julian; Williams, David T; Jasrotia, Rekha; Alexandersen, Soren

    2017-03-14

    Human parechovirus types 1-16 (HPeV1-16) are positive strand RNA viruses in the family Picornaviridae. We investigated a 2015 outbreak of HPeV3 causing illness in infants in Victoria, Australia. Virus genome was extracted from clinical material and isolates and sequenced using a combination of next generation and Sanger sequencing. The HPeV3 outbreak genome was 98.7% similar to the HPeV3 Yamagata 2011 lineage for the region encoding the structural proteins up to nucleotide position 3115, but downstream of that the genome varied from known HPeV sequences with a similarity of 85% or less. Analysis indicated that recombination had occurred, may have involved multiple types of HPeV and that the recombination event/s occurred between March 2012 and November 2013. However the origin of the genome downstream of the recombination site is unknown. Overall, the capsid of this virus is highly conserved, but recombination provided a different non-structural protein coding region that may convey an evolutionary advantage. The indication that the capsid encoding region is highly conserved at the amino acid level may be helpful in directing energy towards the development of a preventive vaccine for expecting mothers or antibody treatment of young infants with severe disease.

  7. Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

    Science.gov (United States)

    Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

    2017-09-01

    To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

  8. Successful use of N-acetylcysteine to treat severe hepatic injury caused by a dietary fitness supplement.

    Science.gov (United States)

    El Rahi, Cynthia; Thompson-Moore, Nathaniel; Mejia, Patricia; De Hoyos, Patricio

    2015-06-01

    In the absence of adequate premarketing efficacy and safety evaluations, adverse events from over-the-counter supplements are emerging as a public health concern. Specifically, bodybuilding products are being identified as a frequent cause of drug-induced liver injury. We present a case of a 20-year-old Hispanic male who presented with acute nausea and vomiting accompanied by severe right upper quadrant abdominal pain, shivering, and shortness of breath. Laboratory data pointed to mixed cholestatic and hepatocellular damage, and after exclusion of known alternate etiologies, the patient was diagnosed with acute drug-induced liver injury secondary to the use of "Friction," a bodybuilding supplement. Treatment with N-acetylcysteine (NAC) 20% oral solution was initiated empirically at a dose of 4000 mg [DOSAGE ERROR CORRECTED] (70 mg/kg) every 4 hours and was continued once the diagnosis was made. Within 48 hours of admission to our hospital, the patient began to show clinical resolution of right abdominal pain and tolerance to oral diet associated with a significant decline toward normal in his liver function tests and coagulopathy. The WHO-UMC causality assessment system suggested a "certain causality" between exposure to the supplement and the acute liver injury. In the event of suspected drug-induced liver injury, treatment with NAC should be considered given its favorable risk-benefit profile. © 2015 Pharmacotherapy Publications, Inc.

  9. Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency

    Directory of Open Access Journals (Sweden)

    Neal Sondheimer

    2017-09-01

    Full Text Available Coenzyme Q10 (CoQ10 or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10–dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ10 biosynthesis. To date, mutations in COQ1 (PDSS1 and PDSS2, COQ2, COQ4, COQ6, COQ7, COQ8A/ADCK3, COQ8B/ADCK4, and COQ9 genes have been identified in patients with primary form of CoQ10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ10 deficiency.

  10. Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency.

    Science.gov (United States)

    Sondheimer, Neal; Hewson, Stacy; Cameron, Jessie M; Somers, Gino R; Broadbent, Jane Dunning; Ziosi, Marcello; Quinzii, Catarina Maria; Naini, Ali B

    2017-09-01

    Coenzyme Q 10 (CoQ 10 ) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ 10 synthesis are usually associated with the impaired function of CoQ 10 -dependent complexes I, II and III. The recessively transmitted CoQ 10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ 10 biosynthesis. To date, mutations in COQ1 ( PDSS1 and PDSS2 ), COQ2 , COQ4 , COQ6 , COQ7 , COQ8A / ADCK3 , COQ8B/ADCK4 , and COQ9 genes have been identified in patients with primary form of CoQ 10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ 10 deficiency.

  11. Hemodialysis-associated neutropenia and hypoxemia: the effect of dialyzer membrane materials.

    Science.gov (United States)

    Hakim, R M; Lowrie, E G

    1982-01-01

    The fall in white blood cells (WBC) and arterial oxygen pressure that occurs during hemodialysis was investigated as a function of different dialysis membranes and different sterilization methods. 8 chronic hemodialysis patients were studied and each was dialyzed with three different membranes: cellulosic hollow fiber, polyacrylonitrile flat sheet and polymethylmethacrylate hollow fiber. Each dialyzer was studied with a dry sterilization method and after formalin treatment. Arterialized blood gas, bicarbonate and WBC were drawn at various intervals throughout dialysis. The effect of the sterilization method was minimal. Cellulosic membranes were shown to cause significantly more neutropenia (p less than 0.001) and hypoxemia (p less than 0.01) than the other two membranes. No significant differences was seen in pH, PCO2 and bicarbonate. The results indicate differences in biocompatibility between different membranes. Clinical implications are discussed.

  12. Novas diretrizes na abordagem clínica da neutropenia febril e da sepse em oncologia pediátrica New guidelines for the clinical management of febrile neutropenia and sepsis in pediatric oncology patients

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2007-05-01

    precoce são fundamentais para a melhora da sobrevida.OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and therapeutic management of febrile neutropenia and sepsis in children with oncological diseases, with special attention to new protocols and guidelines. SOURCES: A review of the scientific literature utilizing an electronic bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED using the keywords febrile, neutropenic, cancer, children, sepsis, intensive, care. Articles published between 1987 and 2007 were selected, with preference given to review articles, protocols, systematic reviews, epidemiological studies, task force recommendations and phase III clinical trials. Consensus documents published by the Infectious Diseases Society of America, the Center for Diseases Control and the Infectious Diseases Working Party of the German Society of Hematology and Oncology, in addition to the recommendations of the World Federation of Pediatric Intensive and Critical Care Societies and Society of Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of aggressive chemotherapy regimens, bone marrow transplantation and intensive care resources have increased the survival rates of children with cancer and also their infectious morbidity, with septic complications as the principal cause of mortality. Several risk factors have been identified, such as neutropenia, oncology type, clinical signs and inflammatory response markers (polymerase chain reaction, procalcitonin and also increased resistance to antimicrobials and antifungal agents. Protocols for risk classification, diagnosis and treatment should be established at each service, taking into account the microbiological flora of each population. Pediatric intensive care has increased the short and long-term survival of these patients. CONCLUSIONS: Oncology patients are particularly vulnerable to infectious complications. Early identification and treatment are

  13. Neutropenia and agranulocytosis in England and Wales: incidence and risk factors

    NARCIS (Netherlands)

    van Staa, T. P.; Boulton, F.; Cooper, C.; Hagenbeek, A.; Inskip, H.; Leufkens, H. G. M.

    2003-01-01

    The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or

  14. CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2012-10-01

    Full Text Available We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

  15. Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

    Science.gov (United States)

    Mhaskar, Rahul; Clark, Otavio Augusto Camara; Lyman, Gary; Engel Ayer Botrel, Tobias; Morganti Paladini, Luciano; Djulbegovic, Benjamin

    2014-10-30

    Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897

  16. Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients

    NARCIS (Netherlands)

    Vos, Xander G.; Smit, Natalie; Endert, Erik; Brosschot, Jos F.; Tijssen, Jan G. P.; Wiersinga, Wilmar M.

    2009-01-01

    Objective: The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but

  17. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia.

    Science.gov (United States)

    Nustede, Rainer; Klimiankou, Maksim; Klimenkova, Olga; Kuznetsova, Inna; Zeidler, Cornelia; Welte, Karl; Skokowa, Julia

    2016-01-01

    A number of studies have demonstrated induction of the unfolded protein response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is unclear. We evaluated the effects of ELANE mutants on UPR induction in myeloid cells from CN and CyN patients, and analysed whether additional CN-specific defects contribute to the differences in UPR induction between CN and CyN patients harbouring identical ELANE mutations. We investigated CN-specific p.C71R and p.V174_C181del (NP_001963.1) and CN/CyN-shared p.S126L (NP_001963.1) ELANE mutants. We found that transduction of haematopoietic cells with p.C71R, but not with p.V174_C181del or p.S126L ELANE mutants induced expression of ATF6, and the ATF6 target genes PPP1R15A, DDIT3 and HSPA5. Recently, we found that levels of secretory leucocyte protease inhibitor (SLPI), a natural ELANE inhibitor, are diminished in myeloid cells from CN patients, but not CyN patients. Combined knockdown of SLPI by shRNA and transduction of ELANE p.S126L in myeloid cells led to elevated levels of ATF6, PPP1R15A and HSPA5 RNA, suggesting that normal levels of SLPI in CyN patients might protect them from the UPR induced by mutant ELANE. In summary, different ELANE mutants have different effects on UPR activation, and SLPI regulates the extent of ELANE-triggered UPR. © 2015 John Wiley & Sons Ltd.

  18. Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Wiesmeier

    Full Text Available Severe congenital neutropenia (SCN is characterised by a differentiation block in the bone marrow and low neutrophil numbers in the peripheral blood, which correlates with increased risk of bacterial infections. Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE gene are frequently found in SCN and cyclic neutropenia. Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR have been proposed to be responsible for neutrophil survival and maturation defects. However, the detailed molecular mechanisms still remain unclear, in part due to the lack of appropriate in vitro and in vivo models. Here we used a system of neutrophil differentiation from immortalised progenitor lines by conditional expression of Hoxb8, permitting the generation of mature near-primary neutrophils in vitro and in vivo. NE-deficient Hoxb8 progenitors were reconstituted with murine and human forms of typical NE mutants representative of SCN and cyclic neutropenia, and differentiation of the cells was analysed in vitro and in vivo. ER stress induction by NE mutations could be recapitulated during neutrophil differentiation in all NE mutant-reconstituted Hoxb8 cells. Despite ER stress induction, no change in survival, maturation or function of differentiating cells expressing either murine or human NE mutants was observed. Further analysis of in vivo differentiation of Hoxb8 cells in a murine model of adoptive transfer did not reveal any defects in survival or differentiation in the mouse. Although the Hoxb8 system has been found to be useful for dissection of defects in neutrophil development, our findings indicate that the use of murine systems for analysis of NE-mutation-associated pathogenesis is complicated by differences between humans and mice in the physiology of granulopoiesis, which may go beyond possible

  19. Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

    Science.gov (United States)

    Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

    2013-08-01

    Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

  20. Higher Total Serum Cholesterol Levels Are Associated With Less Severe Strokes and Lower All-Cause Mortality

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Christensen, Rune Haubo Bojesen; Kammersgaard, Lars

    2007-01-01

    Background and Purpose - Evidence of a causal relation between serum cholesterol and stroke is inconsistent. We investigated the relation between total serum cholesterol and both stroke severity and poststroke mortality to test the hypothesis that hyperch....

  1. Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients.

    Science.gov (United States)

    Vos, Xander G; Smit, Natalie; Endert, Erik; Brosschot, Jos F; Tijssen, Jan G P; Wiersinga, Wilmar M

    2009-02-01

    The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but also self-reported stress. We tested the hypothesis whether advancing age is associated with less exposure to stress, resulting in a lower immunological response, and less severe Graves' hyperthyroidism. Cross-sectional multicenter study. Two hundred and sixty-three consecutive untreated patients with a first episode of Graves' hyperthyroidism were included. The severity of Graves' hyperthyroidism was evaluated biochemically (freeT(4)-index and freeT(3)-index, thyrotropin-binding inhibitory immunoglobulin (TBII)) and clinically by the hyperthyroid symptom scale score (HSS score). Stress exposure was quantitated by three questionnaires. Advancing age was associated with less severe Graves' hyperthyroidism, both biochemically by lower serum freeT(3)-index and freeT(4)-index (Phyperthyroidism. Advancing age was associated with lower scores for stress exposure. Multivariate regression analysis showed that HSS score was independently related to the tendency to report negative feelings (Phyperthyroidism. Because no direct relationship exists between stress exposure and TBII or freeT(3)-index and freeT(4)-index, we reject our hypothesis that less stress is causally related to biochemically less severe Graves' hyperthyroidism in old age. HSS score is primarily determined by negative feelings and not by age.

  2. [Association of atypical pulmonary TB, polyserositis, severe leukopenia and panniculitis. Case report].

    Science.gov (United States)

    Mihălţan, F; Lupu, A; Ungureanu, D; Halic, G; Badea, C; Marcu, C

    2001-01-01

    Many reports have associated tuberculosis with haematological abnormalities. These reports suggest that severe pulmonary tuberculosis, if associated with reduced tissue cellular reaction, may cause blood discrasias. Anemia was present in 32 percent of patients. Leucopenia with neutropenia and lymphopenia was observed in 15 percent in patients with very severe clinical tuberculosis. Active tuberculosis was associated with significant reductions in absolute numbers of total T, T4 and B lymphocytes, but there were no significant differences in total T8 counts. T4 lymphopenia causes reversal of T4/T8 ratio. Also, many histopathologic diagnosis of panniculitis have been reported in tuberculosis patients--the incidence of panniculitis caused by tuberculosis was 8.2%. We present a case of secondary pulmonary tuberculosis with atypically Rx changes, associated with polyserositis and severe leucopenia, which debuted with a panniculitis.

  3. Evaluation of the Incidence and Severity of Olive Leaf Spot caused by Spilocaea oleaginain different olive cultivars in Palestine

    Directory of Open Access Journals (Sweden)

    Ruba Abuamsha

    2013-12-01

    Full Text Available Twelve olive (Olea europaea L. cultivars including Nabali Baladi, Nabali Mohassan, Santa Augustino, Nasohi Jaba`a 1, Nasohi Jaba`a 2, Yunani, Talmasani, Chemlali, Arbequino, Frantoio, Coca and Barouni, were sampled for their susceptibility to Spilocaea oleagina the causal agent for Olive leaf spot (OLS disease on olive trees in Palestine. Investigations were carried out to measure the incidence and severity of the disease at Qabatyia station in Jenin district area Susceptible olive cultivars grown commercially in Palestine include Arbequino, Frantoio and ?Barouni’.The “Nabali” is the most dominant and highly susceptible olive cultivar grown in Palestine. Disease incidence varied greatly among the cultivars F=59.4, df=11, 251, p?0.0001 and was correlated with the severity (y = 0.42x + 9.3, P ? 0.0001, R² = 0.84, y = disease severity and x = disease incidence. Disease severity also varied among different cultivars F=13.9, df=11, 251, p?0.0001. Nabali Mohassan was the most affected susceptible while Barouni was most resistant. Progress of disease severity over time fit the logistic function for all cultivars except for highly susceptible cultivars F=1.56, df=6, 83, p?0.169. The assessment method may be useful to screen olive cultivars for OLS resistance in Palestine.

  4. Prevalence and causes of severe visual impairment and blindness among children in the lorestan province of iran, using the key informant method.

    Science.gov (United States)

    Razavi, Hessom; Kuper, Hannah; Rezvan, Farhad; Amelie, Khatere; Mahboobi-Pur, Hassan; Oladi, Mohammad Reza; Muhit, Mohammad; Hashemi, Hassan

    2010-03-01

    To estimate the prevalence and causes of severe visual impairment and blindness among children in Lorestan province of Iran, and to assess the feasibility of the Key Informant Method in this setting. Potential cases were identified using the Key Informant Method, in 3 counties of Lorestan province during June through August 2008, and referred for examination. Causes of severe visual impairment/blindness were determined and categorized using standard World Health Organization methods. Of 123 children referred for examination, 27 children were confirmed to have severe visual impairment/blindness or blindness. The median age was11 years (interquartile range 6-13), and 59% were girls. After adjusting for non-attenders, the estimated prevalence of severe visual impairment/blindness was 0.04% (0.03-0.05). The main site of abnormality was retina (44%), followed by disorders of the whole eye (33%). The majority of causes had a hereditary etiology (70%), which was associated with a family history of blindness (P = 0.002). Potentially avoidable causes of severe visual impairment/blindness were found in 14 children (52%). Almost all children with severe visual impairment/blindness had a history of parental consanguinity (93%). Our findings suggest a moderate prevalence of childhood blindness in the Lorestan province of Iran, a high proportion of which may be avoidable, given improved access to ophthalmic and genetic counselling services in rural areas. The Key Informant Method is feasible in Iran; future research is discussed.

  5. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause

    Directory of Open Access Journals (Sweden)

    Jérôme Franques

    2017-03-01

    Full Text Available Vitamin B12 (B12 deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.

  6. Anesthetic management of a patient with sustained severe metabolic alkalosis and electrolyte abnormalities caused by ingestion of baking soda.

    Science.gov (United States)

    Soliz, Jose; Lim, Jeffrey; Zheng, Gang

    2014-01-01

    The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies.

  7. Optico-cochleo-dentate degeneration associated with severe peripheral neuropathy and caused by peroxisomal D-bifunctional protein deficiency

    NARCIS (Netherlands)

    Schröder, J. M.; Hackel, V.; Wanders, R. J. A.; Göhlich-Ratmann, G.; Voit, T.

    2004-01-01

    The clinical, neuroradiological, neuropathological and biochemical findings in a patient with optico-cochleo-dentate degeneration (OCDD; OMIM 258700) are presented in a severe case succumbing at the age of 4 years. The electron microscopic and biochemical data showed for the first time that OCDD may

  8. Anesthetic Management of a Patient with Sustained Severe Metabolic Alkalosis and Electrolyte Abnormalities Caused by Ingestion of Baking Soda

    Directory of Open Access Journals (Sweden)

    Jose Soliz

    2014-01-01

    Full Text Available The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies.

  9. HLA-B*44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population

    Directory of Open Access Journals (Sweden)

    Liciana Xavier Eurico de Alencar

    2013-01-01

    Full Text Available Human leukocyte antigen (HLA alleles have been correlated with susceptibility or resistance to severe dengue; however, few immunogenetic studies have been performed in Latin American (LA populations. We have conducted immunogenetic studies of HLA class I and II alleles in a cohort of 187 patients with DENV-3 infection and confirmed clinical diagnosis of either severe dengue, known as dengue hemorrhagic fever (DHF, or the less severe form, dengue fever (DF, in Recife, Pernambuco, Brazil. An association analysis was performed using Fisher’s association test, with odds ratios (ORs calculated using conditional maximum likelihood estimates. HLA-B*44 (P=0.047, OR = 2.025, 95% CI = 0.97–4.24 was found to be associated with increased susceptibility to DHF in response to DENV-3 infection. In addition, HLA-B*07 (P=0.048, OR = 0.501, one-sided 95% CI = 0–0.99 and HLA-DR*13 (P=0.028, OR = 0.511, one-sided 95% CI = 0–0.91 were found to be associated with resistance to secondary dengue infection by DENV-3. These results suggest that HLA-B*44 supertype alleles and their respective T-cell responses might be involved in susceptibility to severe dengue infections, whereas the HLA-B*07 supertype alleles and DR*13 might be involved in cross-dengue serotype immunity.

  10. Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi (Kirin Brewery Co., Ltd., Gunma (Japan). Pharmaceutical Research Laboratory); Fushiki, Masato

    1994-08-01

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 [mu]g/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author).

  11. Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

    International Nuclear Information System (INIS)

    Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi; Fushiki, Masato.

    1994-01-01

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 μg/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author)

  12. Cause-Specific Mortality after Stroke: Relation to Age, Sex, Stroke Severity, and Risk Factors in a 10-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Mogensen, UB; Olsen, TS; Andersen, KK

    2013-01-01

    We investigated cause-specific mortality in relation to age, sex, stroke severity, and cardiovascular risk factor profile in the Copenhagen Stroke Study cohort with 10 years of follow-up. In a Copenhagen community, all patients admitted to the hospital with stroke during 1992-1993 (n = 988) were.......2% for nonvascular disease. Death after stroke was associated with older age, male sex, greater stroke severity, and diabetes regardless of the cause of death. Previous stroke and hemorrhagic stroke were associated with death by stroke, ischemic heart disease was associated with death by heart/arterial disease...... registered on admission. Evaluation included stroke severity, computed tomography scan, and a cardiovascular risk profile. Cause of death within 10 years according to death certificate information was classified as stroke, heart/arterial disease, or nonvascular disease. Competing-risks analyses were...

  13. A brucellosis case presenting with vesicular and maculopapular rash and febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Selmin Dirgen Çaylak

    2014-03-01

    Full Text Available Brucellosis is a systemic disease in which all kind of tissues and organs can be affected. Brucellosis may present with different symptoms and symptoms are non-specific. A broad spectrum of clinical manifestations can be seen, therefore diagnosis can be difficult. Cutaneous complications and febrile neutropenia have been rarely reported. Here, a rare brucellosis case was reported that he applied with fever, skin eruption and neutropenia. We emphasized that especially in endemic areas brucellosis should always be kept on mind in the differential diagnosis of patient with skin eruption and febril neutropenia.J Microbiol Infect Dis 2014;4(1: 39-41

  14. The Importance of Serum Cytokine Levels in Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    Nuray Buyukberber

    2003-02-01

    Full Text Available The most important evaluation of the neutropenic patients is to determine the risk group. The desired approach to patients with low risks should be either not to hospitalize or to hospitalize for a short period of time which both decreases the cost and exposure to the resistant flora. The early diagnosis of sepsis in patients with high risk may be life saving. Recently, the determination of low and high-risk groups only by the clinical variables is not found to be a reliable method. The laboratory parameters supported by the clinical variables may be more practical. The determination of serum cytokines levels in febrile neutropenia may be helpful for the early risk diagnosis, new treatment approaches, and prognosis. [Archives Medical Review Journal 2003; 12(1.000: 12-19

  15. Perceived causes of severe mental disturbance and preferred interventions by the Borana semi-nomadic population in southern Ethiopia: a qualitative study

    Science.gov (United States)

    2012-01-01

    Background Culture affects the way people conceptualize causes of severe mental disturbance which may lead to a variation in the preferred intervention methods. There is a seemingly dichotomous belief regarding what causes severe mental disturbance: people living in western countries tend to focus mainly on biological and psychosocial risk factors; whereas, in non-western countries the focus is mainly on supernatural and religious factors. These belief systems about causation potentially dictate the type of intervention preferred. Studying such belief systems in any society is expected to help in planning and implementation of appropriate mental health services. Methods A qualitative study was conducted among the Borana semi-nomadic population in southern Ethiopia to explore perceived causes of severe mental disturbance and preferred interventions. We selected, using purposive sampling, key informants from three villages and conducted a total of six focus group discussions: three for males and three for females. Results The views expressed regarding the causes of mental disturbance were heterogeneous encompassing supernatural causes such as possession by evil spirits, curse, bewitchment, ‘exposure to wind’ and subsequent attack by evil spirit in postnatal women and biopsychosocial causes such as infections (malaria), loss, ‘thinking too much’, and alcohol and khat abuse. The preferred interventions for severe mental disturbance included mainly indigenous approaches, such as consulting Borana wise men or indigenous healers, prayer, holy water treatment and seeking modern mental health care as a last resort. Conclusions These findings will be of value for health care planners who wish to expand modern mental health care to this population, indicating the need to increase awareness about the causes of severe mental disturbance and their interventions and collaborate with influential people and indigenous healers to increase acceptability of modern mental

  16. Beliefs about causes, symptoms, and stigma associated with severe mental illness among 'highly acculturated' Chinese-American patients.

    Science.gov (United States)

    Lin, Susan Y

    2013-12-01

    Literature about experiences of mental illness among ethnic minority has tended to focus on first-generation migrants. This study fills that gap by exploring experiences among highly acculturated Chinese-American patients with mental illness. Twenty-nine participants completed semi-structured interviews based on Kleinman's explanatory model, which were audio-taped, transcribed and coded for qualitative analysis. Beliefs about the causes of mental illness included biological factors, head trauma and personal losses. Issues relating to stigma and shame were also discussed. Highly acculturated ethnic minority patients may ascribe to a biomedical model at the same time as ascribing to culture-specific beliefs.

  17. Periarticular Morphine-Induced Sphincter of Oddi Spasm Causing Severe Pain and Bradycardia in an Awake Patient Under Spinal Anesthesia: An Important Diagnostic Consideration.

    Science.gov (United States)

    Koumpan, Yuri; Engen, Dale; Tanzola, Robert; Saha, Tarit

    2016-10-01

    Sphincter of Oddi spasm from opioids has been documented, presenting as severe epigastric pain and potentially overlooked in a differential diagnosis. We present a case of sphincter of Oddi spasm from periarticular morphine in a patient under spinal anesthesia, causing severe distress and treated effectively with glucagon. It is important for anesthesiologists using opioids to consider it as a cause of perioperative pain and be familiar with treatment as it may be refractory by conventional use of opioids for pain relief. It is also important to consider the systemic effects of periarticular absorption, as evident by our case.

  18. Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway.

    Science.gov (United States)

    Zhang, Qing; Kaga, Kimitaka; Hayashi, Akimasa

    2011-07-01

    A 27-year-old female showed auditory agnosia after long-term severe hydrocephalus due to congenital spina bifida. After years of hydrocephalus, she gradually suffered from hearing loss in her right ear at 19 years of age, followed by her left ear. During the time when she retained some ability to hear, she experienced severe difficulty in distinguishing verbal, environmental, and musical instrumental sounds. However, her auditory brainstem response and distortion product otoacoustic emissions were largely intact in the left ear. Her bilateral auditory cortices were preserved, as shown by neuroimaging, whereas her auditory radiations were severely damaged owing to progressive hydrocephalus. Although she had a complete bilateral hearing loss, she felt great pleasure when exposed to music. After years of self-training to read lips, she regained fluent ability to communicate. Clinical manifestations of this patient indicate that auditory agnosia can occur after long-term hydrocephalus due to spina bifida; the secondary auditory pathway may play a role in both auditory perception and hearing rehabilitation.

  19. Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.

    Directory of Open Access Journals (Sweden)

    Jenniffer Angulo

    2017-07-01

    Full Text Available Andes virus (ANDV is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1β concentration were observed in ANDV-infected patients (p = 0.9672, whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001. Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively. Notably, IL-6 levels were significantly higher (40-fold in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001. Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3-63.1. In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.

  20. Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements

    OpenAIRE

    Whibley, Annabel; Urquhart, Jill; Dore, Jonathan; Willatt, Lionel; Parkin, Georgina; Gaunt, Lorraine; Black, Graeme; Donnai, Dian; Raymond, F Lucy

    2010-01-01

    Monoamine oxidases (MAO-A and MAO-B) have a key role in the degradation of amine neurotransmitters, such as dopamine, norepinephrine and serotonin. We identified an inherited 240 kb deletion on Xp11.3–p11.4, which encompasses both monoamine oxidase genes but, unlike other published reports, does not affect the adjacent Norrie disease gene (NDP). The brothers who inherited the deletion, and thus have no monoamine oxidase function, presented with severe developmental delay, intermittent hypoton...

  1. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Science.gov (United States)

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

  2. Common Variable Immunodeficiency Caused by FANC Mutations.

    Science.gov (United States)

    Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

    2017-07-01

    Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

  3. Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand

    Directory of Open Access Journals (Sweden)

    Q Sue Huang

    2014-05-01

    Full Text Available Background: Recent experience with pandemic influenza A(H1N1pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. Methods/Design: All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. Discussion: Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9 virus infections and seasonal influenza prevention and control.

  4. Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice

    Science.gov (United States)

    Bassett, J. H. Duncan; Boyde, Alan; Zikmund, Tomas; Evans, Holly; Croucher, Peter I.; Zhu, Xuguang; Park, Jeong Won

    2014-01-01

    A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation. PMID:24914936

  5. Did enhanced afforestation cause high severity peat burn in the Fort McMurray Horse River wildfire?

    Science.gov (United States)

    Wilkinson, S. L.; Moore, P. A.; Flannigan, M. D.; Wotton, B. M.; Waddington, J. M.

    2018-01-01

    Climate change mediated drying of boreal peatlands is expected to enhance peatland afforestation and wildfire vulnerability. The water table depth-afforestation feedback represents a positive feedback that can enhance peat drying and consolidation and thereby increase peat burn severity; exacerbating the challenges and costs of wildfire suppression efforts and potentially shifting the peatland to a persistent source of atmospheric carbon. To address this wildfire management challenge, we examined burn severity across a gradient of drying in a black spruce dominated peatland that was partially drained in 1975-1980 and burned in the 2016 Fort McMurray Horse River wildfire. We found that post-drainage black spruce annual ring width increased substantially with intense drainage. Average (±SD) basal diameter was 2.6 ± 1.2 cm, 3.2 ± 2.0 cm and 7.9 ± 4.7 cm in undrained (UD), moderately drained (MD) and heavily drained (HD) treatments, respectively. Depth of burn was significantly different between treatments (p threshold will aid in developing effective adaptive management techniques and protecting boreal peatland carbon stocks.

  6. Association of oesophageal radiation dose volume metrics, neutropenia and acute radiation oesophagitis in patients receiving chemoradiotherapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Everitt, Sarah; Duffy, Mary; Bressel, Mathias; McInnes, Belinda; Russell, Christine; Sevitt, Tim; Ball, David

    2016-01-01

    The relationship between oesophageal radiation dose volume metrics and dysphagia in patients having chemoradiation (CRT) for non-small cell lung cancer (NSCLC) is well established. There is also some evidence that neutropenia is a factor contributing to the severity of oesophagitis. We retrospectively analysed acute radiation oesophagitis (ARO) rates and severity in patients with NSCLC who received concurrent chemotherapy and high dose radiation therapy (CRT). We investigated if there was an association between grade of ARO, neutropenia and radiation dose volume metrics. Patients with NSCLC having concurrent CRT who had RT dose and toxicity data available were eligible. Exclusion criteria included previous thoracic RT, treatment interruptions and non-standard dose regimens. RT dosimetrics included maximum and mean oesophageal dose, oesophagus dose volume and length data. Fifty four patients were eligible for analysis. 42 (78 %) patients received 60 Gy. Forty four (81 %) patients received carboplatin based chemotherapy. Forty eight (89 %) patients experienced ARO ≥ grade 1 (95 % CI: 78 % to 95 %). ARO grade was associated with mean dose (r s = 0.27, p = 0.049), V20 (r s = 0.31, p = 0.024) and whole oesophageal circumference receiving 20 Gy (r s = 0.32 p = 0.019). In patients who received these doses, V20 (n = 51, r s = 0.36, p = 0.011), V35 (n = 43, r s = 0.34, p = 0.027) and V60 (n = 25, r s = 0.59, P = 0.002) were associated with RO grade. Eleven of 25 (44 %) patients with ARO ≥ grade 2 also had ≥ grade 2 acute neutropenia compared with 5 of 29 (17 %) patients with RO grade 0 or 1 (p = 0.035). In addition to oesophageal dose-volume metrics, neutropenia may also be a risk factor for higher grades of ARO

  7. Incidence and main causes of severe maternal morbidity in São Luís, Maranhão, Brazil: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Ana Paula Pierre Moraes

    Full Text Available CONTEXT AND OBJECTIVE: Evaluation of severe maternal morbidity has been used in monitoring of maternal health. The objective of this study was to estimate its incidence and main causes in São Luís, Maranhão, Brazil. DESIGN AND SETTING: Prospective longitudinal study, carried out in two public high-risk maternity hospitals and two public intensive care units (ICUs for referral of obstetric cases from the municipality. METHODS: Between March 1, 2009, and February 28, 2010, all cases of severe maternal morbidity according to the Mantel and Waterstone criteria were identified. The sociodemographic and healthcare characteristics of the extremely severe cases were compared with the less severe cases, using the Fisher, Χ2, Student t and Mann-Whitney tests, with a significance level of < 0.05. RESULTS: 127 cases of severe maternal morbidity were identified among 8,493 deliveries, i.e. an incidence of 15.0/1000 deliveries. Out of 122 cases interviewed, 121 cases were within the Waterstone criteria and 29 were within the Mantel criteria, corresponding to incidences of 14.1/1000 and 3.4/1000 deliveries, respectively. These rates were lower than those described in the literature, possibly due to case loss. The main causes were hypertension during pregnancy, which was more frequent in less severe cases (P = 0.001 and obstetric hemorrhage, which was more common among extremely severe cases (P = 0.01. CONCLUSIONS: Direct obstetric disorders were the main causes of severe maternal morbidity in São Luís, Maranhão. Investigation and monitoring of severe morbidity may contribute towards improving obstetric care in the municipality.

  8. A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor.

    Science.gov (United States)

    Armario, Antonio; Vallès, Astrid; Dal-Zotto, Silvina; Márquez, Cristina; Belda, Xavier

    2004-09-01

    Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild

  9. Increasing severity of damage caused by floods in the Spanish Mediterranean coast (1960-2014), climate change or vulnerability?

    Science.gov (United States)

    Perez, Alfredo; Gil, Salvador; Lopez, Francisco; Barriendos, Mariano

    2016-04-01

    In recent decades, there has been an increase in physical and economic losses (WMO, CRED and UCL, 2014) that raises serious concerns in society. Climate change projections may explain the rise in flood losses; however, these shouldn't be considered yet (Bouwer, 2011). According to IPCC (2014), there is low confidence in anthropogenic climate change affecting the frequency and magnitude of fluvial floods on a global scale. In other words, this increase in flood events is not completely related to the higher frequency of heavy rainfall. To illustrate the aforementioned, a spatial example can be seen in the study area. In the Spanish Mediterranean coast, we see an increase in economic losses within the last 50 years due to flood events (Gil et al., 2014). It seems that the socio-economic growth and the rise of housing construction (Gaja, 2008) have led to an increase in vulnerability and exposure which are mainly responsible for those losses and the increase in severity of flood events (Pérez et al., 2015). Furthermore, this situation will probably become more precarious if some climate forecasts are met [IPCC, 2014; AEMET, 2015], and if the economic model fails to adopt efficient adaptive measures. Therefore, it is interesting to focus attention on social factors either within the present or future scenario in order to minimise the potential consequences and improve the adaptation. The main objective of this work focuses on the study of the evolution of the severity of the floods in the Spanish Mediterranean coast for the period (1960-2015). To do that, a statistical analysis of the data base [Gil et al., 2014; extended to the entire Spanish Mediterranean coast (MEDIFLOOD)] and a multiscale mapping (local, provincial and regional level) of the frequency of these events will take place in order to make comparisons and show spatiotemporal patterns according to the severity events evolution. Preliminary results show some interesting statistically significant

  10. Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations

    Science.gov (United States)

    Boissel, Sarah; Reish, Orit; Proulx, Karine; Kawagoe-Takaki, Hiroko; Sedgwick, Barbara; Yeo, Giles S.H.; Meyre, David; Golzio, Christelle; Molinari, Florence; Kadhom, Noman; Etchevers, Heather C.; Saudek, Vladimir; Farooqi, I. Sadaf; Froguel, Philippe; Lindahl, Tomas; O'Rahilly, Stephen; Munnich, Arnold; Colleaux, Laurence

    2009-01-01

    FTO is a nuclear protein belonging to the AlkB-related non-haem iron- and 2-oxoglutarate-dependent dioxygenase family. Although polymorphisms within the first intron of the FTO gene have been associated with obesity, the physiological role of FTO remains unknown. Here we show that a R316Q mutation, inactivating FTO enzymatic activity, is responsible for an autosomal-recessive lethal syndrome. Cultured skin fibroblasts from affected subjects showed impaired proliferation and accelerated senescence. These findings indicate that FTO is essential for normal development of the central nervous and cardiovascular systems in human and establish that a mutation in a human member of the AlkB-related dioxygenase family results in a severe polymalformation syndrome. PMID:19559399

  11. Severe hypokinesis caused by paraneoplastic anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes.

    Science.gov (United States)

    Matsumoto, Lumine; Yamamoto, Tomotaka; Higashihara, Mana; Sugimoto, Izumi; Kowa, Hisatomo; Shibahara, Junji; Nakamura, Koichiro; Shimizu, Jun; Ugawa, Yoshikazu; Goto, Jun; Dalmau, Josep; Tsuji, Shoji

    2007-04-15

    We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic "carcinoma in situ" of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits.

  12. Cost Minimization Analysis of the Use of Meropenem and Ceftazidime in Febrile Neutropenia Therapy

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    Rizky Abdulah

    2016-06-01

    Full Text Available Use of antibiotics is required in febrile neutropenia therapy. The variety choice on the use of antibiotics has increased the role of pharmacoeconomics study to determine the most effective and efficient antibiotic in a specific area. The purpose of this study was to investigate the lowest cost antibiotic between meropenem and ceftazidime that were used as one of febrile neutropenia treatments at one of referral hospitals in West Java province during 2011–2013. This study was a retrospective, observational and analytical study that was performed on February 2014 by collecting medical record data related to febrile neutropenia inpatient who received meropenem or ceftazidime therapy. The result showed that although it was not statistically significant, the total cost for ceftazidime therapy was IDR7,082,523, which was lower than meropenem therapy (IDR11,094,147. Hopefully, this result can assist the health professionals in the management of febrile neutropenia therapy.

  13. Neutropenia associated with osteomyelitis due to Hepatozoon canis infection in a dog.

    Science.gov (United States)

    Shimokawa Miyama, Takako; Umeki, Saori; Baba, Kenji; Sada, Kumiko; Hiraoka, Hiroko; Endo, Yasuyuki; Inokuma, Hisashi; Hisasue, Masaharu; Okuda, Masaru; Mizuno, Takuya

    2011-10-01

    A 4-year-old, intact male Shiba dog was referred to Yamaguchi University Animal Medical Center, Yamaguchi, Japan, for the following complaints: anorexia, lethargy, intermittent fever, gingival bleeding and abdominal purpura. The dog presented with persistent neutropenia. Histopathological examination of a bone marrow sample revealed round to oval structures that resembled Hepatozoon micromerozoites and formed a "wheel-spoke" pattern. Furthermore, mature neutrophils were observed around these structures. PCR and sequencing using bone marrow aspirate confirmed Hepatozoon canis (H. canis) infection. These findings suggest that the neutropenia observed in this case was associated with osteomyelitis due to H. canis infection. This is the first report of neutropenia associated with H. canis infection. H. canis infection can be included in the differential diagnosis in canine cases of neutropenia in areas where the disease is endemic.

  14. [A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

    Science.gov (United States)

    Ikegaya, Satoshi; Iwasaki, Hiromichi; Kinoshita, Keiichi; Urasaki, Yoshimasa; Tsutani, Hiroshi; Ueda, Takanori

    2004-03-01

    Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

  15. Familial benign chronic neutropenia associated with periodontal disease. A case report.

    Science.gov (United States)

    Deasy, M J; Vogel, R I; Macedo-Sobrinho, B; Gertzman, G; Simon, B

    1980-04-01

    A rare case report of periodontal disease associated with familial benign chronic neutropenia is presented. The medical, dental and family histories as well as clinical and histologic observations are described and discussed.

  16. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

    Science.gov (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

    2016-11-03

    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  17. Causes of severe visual impairment and blindness in children in schools for the blind in eastern Africa: changes in the last 14 years.

    Science.gov (United States)

    Njuguna, Margaret; Msukwa, Gerald; Shilio, Bernadeth; Tumwesigye, Cillasy; Courtright, Paul; Lewallen, Susan

    2009-01-01

    To determine the causes of severe visual impairment and blindness in children attending schools for the blind in Kenya, Malawi, Uganda, and Tanzania and to compare the findings with those of a 1994 study. Children attending schools for the blind or annexes in 4 eastern African countries were examined. The major anatomical site of and underlying etiology of severe visual impairment and blindness was recorded using the standardized World Health Organization (WHO) reporting form. A total of 1062 children aged below 16 years were examined of whom 701 (65.2%) had severe visual impairment or blindness. The major anatomical sites of visual loss overall (% and 95% CI) were cornea scar/phthisis bulbi (19%,16.1-21.9), whole globe lesions (15.7%,13.0-18.4), retina (15.4 %, 12.7-18.1), lens related disorders (13.1%, 10.7-15.5), and optic nerve disorders (12.3%, 9.9-14.7). Corneal scar/phthisis was not distributed equally among the countries and was highest in Malawi, similar to findings in 1995. The major etiology of visual loss was childhood factors (29.9%) and an estimated 40% of severe visual impairment and blindness was due to potentially avoidable causes. The major causes of severe visual impairment and blindness overall have not changed appreciably since 1995. There are important differences among countries, however, and using overall estimates for planning may be misleading.

  18. Reprodaetion of an animal model of multiple intestinal injuries mimicking "lethal triad" caused by severe penetrating abdominal trauma

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    Peng-fei WANG

    2011-03-01

    Full Text Available Objective To reproduce an animal model of multi-intestinal injuries with "lethal triad" characterized by low body temperature,acidosis and coagulopathy.Methods Six female domestic outbred pigs were anesthetized,and the carotid artery and jugular vein were cannulated for monitoring the blood pressure and heart rate and for infusion of fluid.The animals were shot with a gun to create a severe penetrating abdominal trauma.Immediately after the shooting,50% of total blood volume(35ml/kg hemorrhage was drawn from the carotid artery in 20min.After a 40min shock period,4h of pre-hospital phase was mimicked by normal saline(NS resuscitation to maintain systolic blood pressure(SBP > 80mmHg or mean arterial pressure(MAP > 60mmHg.When SBP > 80mmHg or MAP > 60mmHg,no fluid infusion or additional bleeding was given.Hemodynamic parameters were recorded,and pathology of myocardium,lung,small intestine and liver was observed.Results There were multiple intestinal perforations(8-10 site injuries/pig leading to intra-abdominal contamination,mesenteric injury(1-2 site injuries/pig resulted in partial intestinal ischemia and intra-abdominal hemorrhage,and no large colon and mesenteric vascular injury.One pig died before the completion of the model establishment(at the end of pre-hospital resuscitation.The typical symptoms of trauma-induced hemorrhagic shock were observed in survival animals.Low temperature(33.3±0.5℃,acidosis(pH=7.242±0.064,and coagulopathy(protrombin time and activated partial thromboplasting time prolonged were observed after pre-hospital resuscitation.Pathology showed that myocardium,lung,small intestine and liver were severely injured.Conclusions A new model,simulating three stages of "traumatic hemorrhagic shock,pre-hospital recovery and hospital treatment" and inducing the "lethal triad" accompanied with abdominal pollution,has been successfully established.This model has good stability and high reproducibility.The survival animals can be

  19. A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.

    Science.gov (United States)

    Yamaguchi, Shintaro; Maruyama, Tatsuya; Wakino, Shu; Tokuyama, Hirobumi; Hashiguchi, Akinori; Tada, Shinichiro; Homma, Koichiro; Monkawa, Toshiaki; Thomas, James; Miyashita, Kazutoshi; Kurihara, Isao; Yoshida, Tadashi; Konishi, Konosuke; Hayashi, Koichi; Hayashi, Matsuhiko; Itoh, Hiroshi

    2015-11-11

    Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not

  20. Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

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    Laura R. R. Ribeiro

    2015-01-01

    Full Text Available Cysteinyl leukotrienes (CysLTs and lipoxins (LXs are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J and susceptible (B10.A mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

  1. Assessment of intrafamilial clinical variability of poikiloderma with neutropenia by a 10-year follow-up of three affected siblings.

    Science.gov (United States)

    Concolino, Daniela; Sestito, Simona; Falvo, Francesca; Romano, Giusy; Ceravolo, Miriam; Anastasio, Elisa; Pensabene, Licia; Colombo, Elisa A; Larizza, Lidia

    2018-05-23

    Clericuzio-type poikiloderma with neutropenia is a well-defined nosological entity, but despite a remarkable number of clinical reports, no long term follow-up data has been presented to date regarding patients with this rare condition. Here we describe the results of clinical follow-up of three siblings, one male (Patient 1) and two females (Patients 2 and 3), subsequent to their first clinical and then molecular diagnosis of Clericuzio-type poikiloderma with neutropenia syndrome due to mutation of USB1gene. Patient 1 always expressed the most severe phenotype, while patients 2 and 3 showed an intermediate and mild phenotype, respectively, as observed since their first clinical evaluation. None of the patients developed skin cancer and/or myelodysplastic disorders considering the peripheral haematological findings. Lens opacity, never reported before, was found in two of the three patients. The long term follow-up observations confirm the stability over time of the pronounced intra-familial heterogeneity of clinical manifestations observed prior to and upon molecular diagnosis. We conclude that prolonged follow-up is an adjunct tool to monitor intra-familial variability of PN clinical spectrum which may favour surveillance of more serious complications of the disease among siblings, when a patient-specific clinical expressivity is present. Copyright © 2018. Published by Elsevier Masson SAS.

  2. Mycoplasma ovipneumoniae--a primary cause of severe pneumonia epizootics in the Norwegian Muskox (Ovibos moschatus population.

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    Kjell Handeland

    Full Text Available The Norwegian muskox (Ovibos moschatus population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004-2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two

  3. ENU mutagenesis identifies mice with morbid obesity and severe hyperinsulinemia caused by a novel mutation in leptin.

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    Chen-Jee Hong

    Full Text Available BACKGROUND: Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. Leptin is central to the regulation of energy metabolism and control of body weight in mammals. METHODOLOGY/PRINCIPAL FINDINGS: To better recapitulate the complexity of human obesity syndrome, we applied N-ethyl-N-nitrosourea (ENU mutagenesis in combination with a set of metabolic assays in screening mice for obesity. Mapping revealed linkage to the chromosome 6 within a region containing mouse Leptin gene. Sequencing on the candidate genes identified a novel T-to-A mutation in the third exon of Leptin gene, which translates to a V145E amino acid exchange in the leptin propeptide. Homozygous Leptin(145E/145E mutant mice exhibited morbid obesity, accompanied by adipose hypertrophy, energy imbalance, and liver steatosis. This was further associated with severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperleptinemia, characteristics of human obesity syndrome. Hypothalamic leptin actions in inhibition of orexigenic peptides NPY and AgRP and induction of SOCS1 and SOCS3 were attenuated in Leptin(145E/145E mice. Administration of exogenous wild-type leptin attenuated hyperphagia and body weight increase in Leptin(145E/145E mice. However, mutant V145E leptin coimmunoprecipitated with leptin receptor, suggesting that the V145E mutation does not affect the binding of leptin to its receptor. Molecular modeling predicted that the mutated residue would form hydrogen bond with the adjacent residues, potentially affecting the structure and formation of an active complex with leptin receptor within that region. CONCLUSIONS/SIGNIFICANCE: Thus, our evolutionary, structural, and in vivo metabolic information suggests the residue 145 as of special function significance. The mouse model harboring leptin V145E mutation will provide new information on the current understanding of leptin biology and novel mouse

  4. Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children.

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    Wang, Yanqun; Li, Yamin; Lu, Roujian; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

    2016-03-10

    Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant.

  5. CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

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    Luciana Teofili

    2012-01-01

    Full Text Available

    We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

  6. Flow cytometric analysis of lymphocyte subset in patients with neutropenia among atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Nobutaka; Kimura, Akiro [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1998-12-01

    In 51 patients (atomic bomb survivors 50, unexposed persons 1) who have had neutropenia for two years or more under indistinct cause, cell surface antigen was analyzed by flow cytometry. Twenty-nine cases of survivors were diagnosed as NK cell leukemia or NK cell cytosis because analysis data showed CD3(-), CD56(+) and CD57(+/-). Six cases were diagnosed as NK like T cell hypercytosis because analysis data showed CD3(+), CD56(+/-) and CD57(+). As for 15 cases, CD56(+) cell number was in range of 15.96{+-}5.35 of a normal person, and no relation with NK cell was recognized. But, CD4/CD8 ratio was higher than 2.1, and gain of T helper cell was recognized. One unexposed persons was diagnosed as chronic NK cell leukemia because analysis data showed CD3(-), CD56(+) and CD57(+). Anti-neutrophil antibody wasn't recognized. Cytotoxic activity for K562 and Raji cell line showed high value compared with that of a normal person. Epstein Barr virus wasn't detected. (K.H.)

  7. Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex.

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    Zeng, Ling-Hui; Rensing, Nicholas R; Zhang, Bo; Gutmann, David H; Gambello, Michael J; Wong, Michael

    2011-02-01

    Tuberous Sclerosis Complex (TSC) is an autosomal dominant, multi-system disorder, typically involving severe neurological symptoms, such as epilepsy, cognitive deficits and autism. Two genes, TSC1 and TSC2, encoding the proteins hamartin and tuberin, respectively, have been identified as causing TSC. Although there is a substantial overlap in the clinical phenotype produced by TSC1 and TSC2 mutations, accumulating evidence indicates that TSC2 mutations cause more severe neurological manifestations than TSC1 mutations. In this study, the neurological phenotype of a novel mouse model involving conditional inactivation of the Tsc2 gene in glial-fibrillary acidic protein (GFAP)-positive cells (Tsc2(GFAP1)CKO mice) was characterized and compared with previously generated Tsc1(GFAP1)CKO mice. Similar to Tsc1(GFAP1)CKO mice, Tsc2(GFAP1)CKO mice exhibited epilepsy, premature death, progressive megencephaly, diffuse glial proliferation, dispersion of hippocampal pyramidal cells and decreased astrocyte glutamate transporter expression. However, Tsc2(GFAP1)CKO mice had an earlier onset and higher frequency of seizures, as well as significantly more severe histological abnormalities, compared with Tsc1(GFAP1)CKO mice. The differences between Tsc1(GFAP1)CKO and Tsc2(GFAP1)CKO mice were correlated with higher levels of mammalian target of rapamycin (mTOR) activation in Tsc2(GFAP1)CKO mice and were reversed by the mTOR inhibitor, rapamycin. These findings provide novel evidence in mouse models that Tsc2 mutations intrinsically cause a more severe neurological phenotype than Tsc1 mutations and suggest that the difference in phenotype may be related to the degree to which Tsc1 and Tsc2 inactivation causes abnormal mTOR activation.

  8. High levels of virus replication and an intense inflammatory response contribute to the severe pathology in lymphoid tissues caused by Newcastle disease virus genotype VIId.

    Science.gov (United States)

    Hu, Zenglei; Hu, Jiao; Hu, Shunlin; Song, Qingqing; Ding, Pingyun; Zhu, Jie; Liu, Xiaowen; Wang, Xiaoquan; Liu, Xiufan

    2015-03-01

    Some strains of Newcastle disease virus (NDV) genotype VIId cause more-severe tissue damage in lymphoid organs compared to other virulent strains. In this study, we aim to define the mechanism of this distinct pathological manifestation of genotype VII viruses. Pathology, virus replication, and the innate immune response in lymphoid tissues of chickens infected with two genotype VIId NDV strains (JS5/05 and JS3/05), genotype IX NDV F48E8 and genotype IV NDV Herts/33, were compared. Histopathologic examination showed that JS5/05 and JS3/05 produced more-severe lesions in the spleen and thymus, but these four virulent strains caused comparable mild lesions in the bursa. In addition, JS3/05 and JS5/05 replicated at significantly higher levels in the lymphatic organs than F48E8 and Herts/33. A microarray assay performed on the spleens of chickens infected with JS5/05 or Herts/33 revealed that JS5/05 elicited a more potent inflammatory response by increasing the number and expression levels of activated genes. Moreover, cytokine gene expression profiling showed that JS5/05 and JS3/05 induced a stronger cytokine response in lymphoid tissues compared to F48E8 and Herts/33. Taken together, our results indicate that the severe pathology in immune organs caused by genotype VIId NDV strains is associated with high levels of virus replication and an intense inflammatory response.

  9. Management of Infection and Febrile Neutropenia in Patients with Solid Cancer.

    Science.gov (United States)

    Aguado, José María; Cruz, Juan Jesús; Virizuela, Juan Antonio; Aguilar, Manuela; Carmona, Alberto; Cassinello, Javier; Gudiol, Carlota; Jiménez Fonseca, Paula; Lizasoain, Manuel; Marco, Francesc; Ruiz, Isabel; Ruiz, Maribel; Salavert, Miguel; Vicente, David; Carratalà, Jordi

    A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study

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    Francis Gordon A

    2011-09-01

    Full Text Available Abstract Background Severe hypertriglyceridemia (HTG is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined. Methods and Results A retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772 mg/dl between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%, with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%, with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79% and obesity (47.6% were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24% were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit. Conclusions These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

  11. Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

    Directory of Open Access Journals (Sweden)

    Ellen Krautkrämer

    2016-11-01

    Full Text Available Abstract Background Hantavirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and virus-specific factors are considered. Case presentation We analyzed severe cases of hantavirus disease in two young women. The first case was caused by Puumala virus (PUUV infection in Germany; the second case describes the infection with Dobrava-Belgrade virus (DOBV in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi. The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs, known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2, vascular endothelial growth factor (VEGF, and stromal derived factor-1 (SDF-1α were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Conclusions Severe hantavirus disease caused by different hantavirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  12. Inter-Ethnic Differences in Quantified Coronary Artery Disease Severity and All-Cause Mortality among Dutch and Singaporean Percutaneous Coronary Intervention Patients.

    Directory of Open Access Journals (Sweden)

    Crystel M Gijsberts

    Full Text Available Coronary artery disease (CAD is a global problem with increasing incidence in Asia. Prior studies reported inter-ethnic differences in the prevalence of CAD rather than the severity of CAD. The angiographic "synergy between percutaneous coronary intervention (PCI with taxus and cardiac surgery" (SYNTAX score quantifies CAD severity and predicts outcomes. We studied CAD severity and all-cause mortality in four globally populous ethnic groups: Caucasians, Chinese, Indians and Malays.We quantified SYNTAX scores of 1,000 multi-ethnic patients undergoing PCI in two tertiary hospitals in the Netherlands (Caucasians and Singapore (Chinese, Indians and Malays. Within each ethnicity we studied 150 patients with stable CAD and 100 with ST-elevated myocardial infarction (STEMI. We made inter-ethnic comparisons of SYNTAX scores and all-cause mortality.Despite having a younger age (mean age Indians: 56.8 and Malays: 57.7 vs. Caucasians: 63.7 years, multivariable adjusted SYNTAX scores were significantly higher in Indians and Malays than Caucasians with stable CAD: 13.4 [11.9-14.9] and 13.4 [12.0-14.8] vs. 9.4 [8.1-10.8], p<0.001. Among STEMI patients, SYNTAX scores were highest in Chinese and Malays: 17.7 [15.9-19.5] and 18.8 [17.1-20.6] vs. 15.5 [13.5-17.4] and 12.7 [10.9-14.6] in Indians and Caucasians, p<0.001. Over a median follow-up of 709 days, 67 deaths (stable CAD: 37, STEMI: 30 occurred. Among STEMI patients, the SYNTAX score independently predicted all-cause mortality: HR 2.5 [1.7-3.8], p<0.001 for every 10-point increase. All-cause mortality was higher in Indian and Malay STEMI patients than Caucasians, independent of SYNTAX score (adjusted HR 7.2 [1.5-34.7], p=0.01 and 5.8 [1.2-27.2], p=0.02.Among stable CAD and STEMI patients requiring PCI, CAD is more severe in Indians and Malays than in Caucasians, despite having a younger age. Moreover, Indian and Malay STEMI patients had a greater adjusted risk of all-cause mortality than Caucasians

  13. Appearance of febrile neutropenia episodes after cytostatic therapy on oncology patients

    International Nuclear Information System (INIS)

    Lami Casaus, Leonardo; Arbesu Michelena, Maria Antonieta; Sarmiento, Sofia Alsina; Brito Iglesia, Rosario

    2009-01-01

    Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and the presence of other factors that may to increase the risk to these reactions. A total of 42 patients were studied admitted with febrile neutropenia after above therapy from February to August, 2007. Biomedical variables from included patient group were achieved and the previously applied cytostatic therapy. The prevalent age-group was those patients aged over 50 and predominance of male sex and advanced stages with associated affections. The more frequent tumor locations were in breast, lung, and non-Hodgkin lymphoma. The cytostatic agent more used in cases of febrile neutropenia was Adriamycin (71.4 %) followed by Cyclophosphamide (52.4 %). The factors more associated with febrile neutropenia appearance were: Anthracycline chemotherapy, age over 50, advanced stages, and presence of associated diseases

  14. Microbiology and mortality of pediatric febrile neutropenia in El Salvador.

    Science.gov (United States)

    Gupta, Sumit; Bonilla, Miguel; Gamero, Mario; Fuentes, Soad L; Caniza, Miguela; Sung, Lillian

    2011-05-01

    Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions.

  15. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    Science.gov (United States)

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

  16. Outcome of severe infections in afebrile neutropenic cancer patients

    Science.gov (United States)

    Mahkovic-Hergouth, Ksenija; Novakovic, Barbara Jezersek; Seruga, Bostjan

    2016-01-01

    Abstract Background In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher’s exact test. Results We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Conclusions Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy. PMID:27904453

  17. CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients.

    Science.gov (United States)

    Jähn, Johanna; Caliebe, Almuth; von Spiczak, Sarah; Boor, Rainer; Stefanova, Irina; Stephani, Ulrich; Helbig, Ingo; Muhle, Hiltrud

    2013-07-01

    CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years. All 4 patients had epilepsy starting with focal seizures in the first 3 months of life, evolving to epileptic spasms between the ages of 2 and 6 years and later on to tonic seizures. In 3 patients, epilepsy was resistant to antiepileptic therapy. Although there was no common EEG pattern in all patients, late hypsarrhythmia until the age of 9 years was observed in 2 patients. CDKL5-related epileptic encephalopathies are a group of refractory seizure disorders starting in early infancy. The phenomenon of late hypsarrhythmia may help define a subgroup of patients with severe and adverse outcomes.

  18. Treatment of severe mitral regurgitation caused by lesions in both leaflets using multiple mitral valve plasty techniques in a small dog

    Directory of Open Access Journals (Sweden)

    Satoko Yokoyama

    2017-11-01

    Full Text Available Mitral valve plasty (MVP is preferred over mitral valve replacement (MVR for mitral regurgitation in humans because of its favorable effect on quality of life. In small dogs, it is difficult to repair multiple lesions in both leaflets using MVP. Herein, we report a case of severe mitral regurgitation caused by multiple severe lesions in the posterior leaflet (PL in a mixed Chihuahua. Initially, we had planned MVR with an artificial valve. However, MVP combined with artificial chordal reconstruction of both leaflets, semicircular suture annuloplasty, and valvuloplasty using a newly devised direct scallop suture for the PL was attempted in this dog. The dog recovered well and showed no adverse cardiac signs, surviving two major operations. The dog died 4 years and 10 months after the MVP due to non-cardiovascular disease. Our additional technique of using a direct scallop suture seemed useful for PL repair involving multiple scallops in a small dog.

  19. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

    DEFF Research Database (Denmark)

    Donskov, Frede; Michaelson, M Dror; Puzanov, Igor

    2015-01-01

    ), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand-foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer...... PFS (P=0.0276 and Pneutropenia was significantly associated...... with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63-0.67) for IMDC classification alone and 0.72 (95% CI: 0.70-0.74) when combined with hypertension and neutropenia...

  20. Outpatient management of febrile neutropenia: time to revise the present treatment strategy

    DEFF Research Database (Denmark)

    Carstensen, M.; Sørensen, Jens Benn

    2008-01-01

    We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low......-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis...... treatment failure (P febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically...

  1. Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

    Science.gov (United States)

    Aggarwal, N; Tee, S A; Saqib, W; Fretwell, T; Summerfield, G P; Razvi, S

    2016-12-01

    Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. Prospective study from August 2010 to December 2014. Endocrinology outpatient clinic in a single centre. Consecutive patients (n = 206) with newly diagnosed GD. ATD therapy. Prevalence and factors predicting neutropenia (treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy. © 2016 John Wiley & Sons Ltd.

  2. The use of rhG-CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history

    NARCIS (Netherlands)

    Kuijpers, T. W.; de Haas, M.; de Groot, C. J.; von dem Borne, A. E.; Weening, R. S.

    1996-01-01

    An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of

  3. Very early discharge versus early discharge versus non-early discharge in children with cancer and febrile neutropenia

    NARCIS (Netherlands)

    Loeffen, Erik A. H.; te Poele, Esther M.; Tissing, Wim J. E.; Boezen, H. Marike; de Bont, Eveline S. J. M.

    2016-01-01

    Background Chemotherapy-induced neutropenia is a common adverse effect in children with cancer. Due to the high relative risk of infections and infectious complications, standard care for children with cancer and febrile neutropenia consists of routine hospitalization and parenteral administration

  4. Retinopathy of prematurity as a major cause of severe visual impairment and blindness in children in schools for the blind in Guadalajara city, Mexico.

    Science.gov (United States)

    Zepeda-Romero, L C; Barrera-de-Leon, J C; Camacho-Choza, C; Gonzalez Bernal, C; Camarena-Garcia, E; Diaz-Alatorre, C; Gutierrez-Padilla, J A; Gilbert, C

    2011-11-01

    To determine the causes of blindness in students attending schools for the blind in Guadalajara city, Mexico and to assess the availability of screening for retinopathy of prematurity (ROP) in local neonatal intensive care units. Information on causes of blindness was obtained by interview with parents and teachers, review of records and examination. Causes of visual loss in children with a distance visual acuity of blind) were determined and classified according to the WHO's classification system for children. Of 153 children in the two participating schools, 144 were severely visual impaired or blind. Their ages ranged from 4 months to 15 years and 58% were female. ROP was the most common cause of visual loss (34.7%), followed by optic nerve lesions (17.4%) and glaucoma (14.6%). 25/59 (42.3%) children aged 0-4 years were blind from ROP compared with 6/32 (18.8%) children aged 10-15 years. 78% of children blind from ROP had psychomotor delay and less than half (46%) had not received treatment for ROP. All five privately funded neonatal intensive care units in the city regularly screen for ROP compared with only four of the 12 units in the public sector. ROP is the leading cause of blindness in children in Mexico despite national guidelines being in place. Health policies promoting primary prevention through improved neonatal care need to be implemented. Advocacy is required so that the time ophthalmologists spend screening and treating ROP is included in their job description and hence salaried.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

    Directory of Open Access Journals (Sweden)

    Mindy M. Sampson

    2017-01-01

    Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

  7. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history.

    Science.gov (United States)

    Donadieu, Jean; Beaupain, Blandine; Fenneteau, Odile; Bellanné-Chantelot, Christine

    2017-11-01

    This review focuses on the classification, diagnosis and natural history of congenital neutropenia (CN). CN encompasses a number of genetic disorders with chronic neutropenia and, for some, affecting other organ systems, such as the pancreas, central nervous system, heart, bone and skin. To date, 24 distinct genes have been associated with CN. The number of genes involved makes gene screening difficult. This can be solved by next-generation sequencing (NGS) of targeted gene panels. One of the major complications of CN is spontaneous leukaemia, which is preceded by clonal somatic evolution, and can be screened by a targeted NGS panel focused on somatic events. © 2017 John Wiley & Sons Ltd.

  8. Prevalidation of a model for predicting acute neutropenia by colony forming unit granulocyte/macrophage (CFU-GM) assay.

    Science.gov (United States)

    Pessina, A; Albella, B; Bueren, J; Brantom, P; Casati, S; Gribaldo, L; Croera, C; Gagliardi, G; Foti, P; Parchment, R; Parent-Massin, D; Sibiril, Y; Van Den Heuvel, R

    2001-12-01

    This report describes an international prevalidation study conducted to optimise the Standard Operating Procedure (SOP) for detecting myelosuppressive agents by CFU-GM assay and to study a model for predicting (by means of this in vitro hematopoietic assay) the acute xenobiotic exposure levels that cause maximum tolerated decreases in absolute neutrophil counts (ANC). In the first phase of the study (Protocol Refinement), two SOPs were assessed, by using two cell culture media (Test A, containing GM-CSF; and Test B, containing G-CSF, GM-CSF, IL-3, IL-6 and SCF), and the two tests were applied to cells from both human (bone marrow and umbilical cord blood) and mouse (bone marrow) CFU-GM. In the second phase (Protocol Transfer), the SOPs were transferred to four laboratories to verify the linearity of the assay response and its interlaboratory reproducibility. After a further phase (Protocol Performance), dedicated to a training set of six anticancer drugs (adriamycin, flavopindol, morpholino-doxorubicin, pyrazoloacridine, taxol and topotecan), a model for predicting neutropenia was verified. Results showed that the assay is linear under SOP conditions, and that the in vitro endpoints used by the clinical prediction model of neutropenia are highly reproducible within and between laboratories. Valid tests represented 95% of all tests attempted. The 90% inhibitory concentration values (IC(90)) from Test A and Test B accurately predicted the human maximum tolerated dose (MTD) for five of six and for four of six myelosuppressive anticancer drugs, respectively, that were selected as prototype xenobiotics. As expected, both tests failed to accurately predict the human MTD of a drug that is a likely protoxicant. It is concluded that Test A offers significant cost advantages compared to Test B, without any loss of performance or predictive accuracy. On the basis of these results, we proposed a formal Phase II validation study using the Test A SOP for 16-18 additional

  9. 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.

  10. The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

    Science.gov (United States)

    Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

    2012-01-01

    Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

  11. Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

    Science.gov (United States)

    Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

    2017-07-01

    Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.

    Science.gov (United States)

    Baumann, G; Maheshwari, H

    1997-11-01

    We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone-releasing hormone receptor (GHRH-R) locus on chromosome 7. Amplification and sequencing of the GHRH-R gene in affected subjects demonstrated an amber nonsense mutation (GAG-->TAG; Glu50-->Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH-R in its extracellular domain, which is likely to result in a severely disabled or non-existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone-releasing hormone (GHRH)--growth hormone--insulin-like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH-R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.

  13. First two cases of severe multifocal infections caused by Klebsiella pneumoniae in Switzerland: characterization of an atypical non-K1/K2-serotype strain causing liver abscess and endocarditis.

    Science.gov (United States)

    Babouee Flury, Baharak; Donà, Valentina; Buetti, Niccolò; Furrer, Hansjakob; Endimiani, Andrea

    2017-09-01

    We describe the first two multifocal invasive infections due to Klebsiella pneumoniae recently observed in Switzerland. Phenotypic (MIC assays and string test) and molecular analyses (PCR/Sequencing for bla, virulence factor genes and whole genome sequencing for one strain) were performed to characterize the causative K. pneumoniae isolates. Both K. pneumoniae isolates (Kp1 and Kp2) were pan-susceptible to antibiotics and produced narrow-spectrum SHV β-lactamases. However, only Kp1 was string test positive. Kp1 was of ST380 and caused liver abscess as well as pneumonia and orbital phlegmon in an Eritrean patient. It belonged to the hypervirulent capsular serotype K2 and harboured the classic virulence-associated rmpA and aerobactin genes, fulfilling both the clinical and microbiological definitions for an invasive K. pneumoniae syndrome. Kp2 was of ST1043 and caused both liver abscess and endocarditis in a Swiss patient. Moreover, it did not possess the classic virulence-associated genes. Whole genome sequencing identified less well-known virulence factors in Kp2 that might have contributed to its virulence. Among these there were genes important for intestinal colonization and/or invasion, such as genes involved in adhesion (e.g., fimABCD and mrkABCD), regulation of capsule polysaccharide biosynthesis (e.g., evgS-evgA), as well as iron uptake (iroN), energy conversion, and metabolism. This report confirms the continuous dissemination of hypervirulent K. pneumoniae strains among patients of non-Asian descent in Europe. Moreover, it highlights the genetic background of an atypical hypervirulent K. pneumoniae causing a severe invasive infection despite not possessing the classical virulence characteristics of hypermucoviscous strains. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  14. Large armored bridging over fractured vertebra with intraspinal tumor mimicking bony mass caused by migrated fragments of burst cervical vertebra presenting with severe cervical myelopathy

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    Satyarthee Guru Dutta

    2017-06-01

    Full Text Available Vertebral body may get displaced anterior or posteror with elements of rotation. However, burst cervical spine vertebral fracture may migrate anteriorly and posteriorly simultaneously. However anterior displaced fragment forming armor like mass is very rare. Similarly, the posteriorly propelled fragments migrating caudally and posterolaterally producing a large osseous mass inside spinal canal mimicking bony tumour causing severe cervical canal stenosis and presenting with marked myelopathy is extremely rare. To the best knowledge of authors, association of such traumatic dual pathology represents first of its kind in western literature, who was neglected early medical advice and presenting with marked compressive cervical myelopathy. She underwent successful surgical decompression with gradual recovery of spastic limb weakness and recovery of sensation. Authors also highlights the importance of early resuscitation and adequate maintainace of mean arterial pressure following acute spinal cord injury. Pertinent literature is briefly reviewed.

  15. Retinal vascular abnormalities and dragged maculae in a carrier with a new NDP mutation (c.268delC) that caused severe Norrie disease in the proband.

    Science.gov (United States)

    Lin, Phoebe; Shankar, Suma P; Duncan, Jacque; Slavotinek, Anne; Stone, Edwin M; Rutar, Tina

    2010-02-01

    Norrie disease (ND) is caused by mutations in the ND pseudoglioma (NDP) gene (MIM 300658) located at chromosome Xp11.4-p11.3. ND is characterized by abnormal retinal vascular development and vitreoretinal disorganization presenting at birth. Systemic manifestations include sensorineural deafness, progressive mental disorder, behavioral and psychological problems, growth failure, and seizures. Other vitreoretinopathies that are associated with NDP gene mutations include X-linked familial exudative vitreoretinopathy, Coats disease, persistent fetal vasculature, and retinopathy of prematurity. Phenotypic variability associated with NDP gene mutations has been well documented in affected male patients. However, there are limited data on signs in female carriers, with mild peripheral retinal abnormalities reported in both carrier and noncarrier females of families with NDP gene mutations. Here, we report a family harboring a single base-pair deletion, c.268delC, in the NDP gene causing a severe ND phenotype in the male proband and peripheral retinal vascular abnormalities with dragged maculae similar to those observed in familial exudative vitreoretinopathy in his carrier mother. Copyright (c) 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  16. Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2014-01-01

    a fever. OBJECTIVES: To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA...

  17. Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Dalbøge, Christina S

    2014-01-01

    and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were...

  18. A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

    NARCIS (Netherlands)

    Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

    We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

  19. Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Talita Garcia do Nascimento

    2014-04-01

    Full Text Available OBJECTIVES: to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer.METHODS: observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant.RESULTS: 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia.CONCLUSION: neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care.

  20. Cost Effectiveness of Primary Pegfilgrastim Prophylaxis in Patients With Breast Cancer at Risk of Febrile Neutropenia

    NARCIS (Netherlands)

    Aarts, Maureen J.; Grutters, Janneke P.; Peters, Frank P.; Mandigers, Caroline M.; Dercksen, M. Wouter; Stouthard, Jacqueline M.; Nortier, Hans J.; van Laarhoven, Hanneke W.; van Warmerdam, Laurence J.; van de Wouw, Agnes J.; Jacobs, Esther M.; Mattijssen, Vera; van der Rijt, Carin C.; Smilde, Tineke J.; van der Velden, Annette W.; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W.; van Gastel, Saskia M.; Joore, Manuela A.; Borm, George F.; Tjan-Heijnen, Vivianne C.

    2013-01-01

    Purpose Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary

  1. Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia

    NARCIS (Netherlands)

    Aarts, M.J.; Grutters, J.P.C.; Peters, F.P.; Mandigers, C.M.P.W.; Dercksen, M.W.; Stouthard, J.M.; Nortier, H.J.; Laarhoven, H.W.M. van; Warmerdam, L.J. van; Wouw, A.J. van de; Jacobs, E.M.G.; Mattijssen, V.; Rijt, C.C. van der; Smilde, T.J.; Velden, A.W. van der; Temizkan, M.; Batman, E.; Muller, E.W.; Gastel, S.M. van; Joore, M.A.; Borm, G.F.; Tjan-Heijnen, V.C.

    2013-01-01

    PURPOSE: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary

  2. Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

    Science.gov (United States)

    Diorio, Caroline; Martino, Julia; Boydell, Katherine Mary; Ethier, Marie-Chantal; Mayo, Chris; Wing, Richard; Teuffel, Oliver; Sung, Lillian; Tomlinson, Deborah

    2011-01-01

    To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process.

  3. Infusional β-lactam antibiotics in febrile neutropenia: has the time come?

    Science.gov (United States)

    Abbott, Iain J; Roberts, Jason A

    2012-12-01

    Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia. There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings. Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.

  4. Aplicación de un modelo pronóstico para predecir la evolución de la neutropenia febril en niños con leucemias agudas A new model applied in prediction of febrile neutropenia in children with acute leukemias

    Directory of Open Access Journals (Sweden)

    Alberto Arencibia Núñez

    2009-08-01

    Full Text Available Se realizó estudio analítico retrospectivo de casos controles en 62 episodios de neutropenia febril presentados por pacientes con hemopatías malignas admitidos en el Instituto de Hematología e Inmunología durante los años 2005 y 2006. Los episodios de neutropenia febril se dividieron en 2 grupos a partir de su evolución favorable (56 % o desfavorable (44 % y se compilaron los parámetros clínicos y de laboratorio en ambos grupos. Los factores que mayor asociación mostraron con la evolución desfavorable fueron la presencia de comorbilidad (sepsis, deshidratación, hipoxia, hipovolemia, mucositis severa, el diagnóstico de leucemia aguda no linfoblástica, el uso de quimioterapia en los 7 días previos al inicio de la fiebre, el compromiso del estado general, y el conteo absoluto de neutrófilos menor de 100 x mm³. Los pacientes con neutropenia febril de evolución desfavorable presentaron entre 3 y 5 factores de riesgo, mientras que los de evolución satisfactoria tuvieron menos de 2 factores de mal pronóstico. El valor predictivo positivo del modelo pronóstico fue del 91,4 % y el negativo del 92,6 %, con una sensibilidad y especificidad del 94,1 % y 89,3 %, respectivamente.A retrospective and analytical control cases study was carried out in 62 episodes of febrile neutropenia present in patients with malignant blood disease admitted in Hematology and Immunology Institute during 2005 and 2006. Above episodes were divided in 2 groups from its favorable course (56% or unfavorable (44% as well as the laboratory and clinical parameters compiled in both groups. Factors with higher association related to unfavorable course were the comorbidities presence (sepsis, dehydration, hypoxia, hypovolemia and severe mucositis, diagnosis of non-lymphoblastic, use of chemotherapy during the 7 previous days to fever onset, general status involvement, and the neutrophil absolute count lower than 100 x mm³. Patients presenting with a unfavorable course

  5. Outcome of severe infections in afebrile neutropenic cancer patients

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    Strojnik Ksenija

    2016-12-01

    Full Text Available In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia.

  6. Olive anthracnose: a yield- and oil quality-degrading disease caused by several species of Colletotrichum that differ in virulence, host preference and geographical distribution.

    Science.gov (United States)

    Talhinhas, Pedro; Loureiro, Andreia; Oliveira, Helena

    2018-03-08

    Olive anthracnose causes fruit rot leading to its drop or mummification, resulting in yield losses and the degradation of oil quality. The disease is caused by diverse species of Colletotrichum, mostly clustering in the C. acutatum species complex. Colletotrichum nymphaeae and C. godetiae are the prevalent species in the Northern Hemisphere, whereas C. acutatum sensu stricto is the most frequent species in the Southern Hemisphere, although it is recently and quickly emerging in the Northern Hemisphere. The disease has been reported from all continents, but it attains higher incidence and severity in the west of the Mediterranean Basin, where it is endemic in traditional orchards of susceptible cultivars. The pathogens are able to survive on vegetative organs. On the fruit surface, infections remain quiescent until fruit maturity, when typical anthracnose symptoms develop. Under severe epidemics, defoliation and death of branches can also occur. Pathogen species differ in virulence, although this depends on the cultivar. The selection of resistant cultivars depends strongly on pathogen diversity and environmental conditions, posing added difficulties to breeding efforts. Chemical disease control is normally achieved with copper-based fungicides, although this may be insufficient under highly favourable disease conditions and causes concern because of the presence of fungicide residues in the oil. In areas in which the incidence is high, farmers tend to anticipate harvest, with consequences in yield and oil characteristics. Olive production systems, harvest and post-harvest processing have experienced profound changes in recent years, namely new training systems using specific cultivars, new harvest and processing techniques and new organoleptic market requests. Changes are also occurring in both the geographical distribution of pathogen populations and the taxonomic framework. In addition, stricter rules concerning pesticide use are likely to have a strong impact

  7. Neutropenia Inmune - Aloinmune neonatal: IgG sérica reactiva y fenotipo específico de los neutrófilos evaluados por citometría de flujo Autoimmune-alloimmune neonatal neutropenia: Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry

    Directory of Open Access Journals (Sweden)

    Norma E. Riera

    2006-10-01

    Full Text Available La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con los neutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna a los antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20 en reacción autóloga (suero y células de un mismo individuo y heteróloga (suero y células de diferentes individuos. Los resultados se expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilución del suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune.Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4

  8. Viruses causing severe acute respiratory infections (SARI) in children ≤5 years of age at a tertiary care hospital in Rajasthan, India.

    Science.gov (United States)

    Malhotra, Bharti; Swamy, M Anjaneya; Janardhan Reddy, P V; Gupta, M L

    2016-12-01

    Severe acute respiratory infection (SARI) is one of the leading causes of death among children worldwide. As different respiratory viruses exhibit similar symptoms, simultaneous detection of these viruses in a single reaction mixture can save time and cost. The present study was done in a tertiary care children's hospital for rapid identification of viruses causing SARI among children less than or equal to five years of age using multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) kit. A total of 155 throat swabs were collected from equal number of children suspected to have SARI and processed for extraction of nucleic acids using automated extraction system. Multiplex real-time RT-PCR was done to identify the viruses in the samples. The overall positivity for viruses in the study was found to be 72.9 per cent with a co-infection rate of 19.5 per cent. Human metapneumovirus (HMPV) was the predominant virus detected in 25.7 per cent children followed by influenza A (H1N1)pdm09, human rhinovirus (HRV) and human adenovirus (HAdV) in 19.9, 11.0 and 8.8 per cent children, respectively. The HMPV was at its peak in February 2013, HAdV showed two peaks in March-April, 2012 and November 2012-March 2013 while HRV was detected throughout the year. Multiplex real-time PCR helped in rapid identification of viruses. Seventeen viruses were detected in SARI cases with overall positivity of 72.9 per cent. HMPV was the most predominant virus. However, for better clinico-virological correlation, studies are required with complete work up of all the aetiological agents, clinical profile of patients and treatment outcome.

  9. Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

    Science.gov (United States)

    Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

    2017-02-01

    Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies. Copyright © 2017 by the Genetics Society of America.

  10. Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

    Directory of Open Access Journals (Sweden)

    Kontny Udo

    2008-03-01

    Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

  11. A novel splice variant in the N-propeptide of COL5A1 causes an EDS phenotype with severe kyphoscoliosis and eye involvement.

    Directory of Open Access Journals (Sweden)

    Sofie Symoens

    Full Text Available BACKGROUND: The Ehlers-Danlos Syndrome (EDS is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. The classic subtype of EDS is caused by mutations in one of the type V collagen genes (COL5A1 and COL5A2. Most mutations affect the type V collagen helical domain and lead to a diminished or structurally abnormal type V collagen protein. Remarkably, only two mutations were reported to affect the extended, highly conserved N-propeptide domain, which plays an important role in the regulation of the heterotypic collagen fibril diameter. We identified a novel COL5A1 N-propeptide mutation, resulting in an unusual but severe classic EDS phenotype and a remarkable splicing outcome. METHODOLOGY/PRINCIPAL FINDINGS: We identified a novel COL5A1 N-propeptide acceptor-splice site mutation (IVS6-2A>G, NM_000093.3_c.925-2A>G in a patient with cutaneous features of EDS, severe progressive scoliosis and eye involvement. Two mutant transcripts were identified, one with an exon 7 skip and one in which exon 7 and the upstream exon 6 are deleted. Both transcripts are expressed and secreted into the extracellular matrix, where they can participate in and perturb collagen fibrillogenesis, as illustrated by the presence of dermal collagen cauliflowers. Determination of the order of intron removal and computational analysis showed that simultaneous skipping of exons 6 and 7 is due to the combined effect of delayed splicing of intron 7, altered pre-mRNA secondary structure, low splice site strength and possibly disturbed binding of splicing factors. CONCLUSIONS/SIGNIFICANCE: We report a novel COL5A1 N-propeptide acceptor-splice site mutation in intron 6, which not only affects splicing of the adjacent exon 7, but also causes a splicing error of the upstream exon 6. Our findings add further insights into the COL5A1 splicing order and show for the first time that a single COL5A1 acceptor-splice site

  12. Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development.

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    Christopher Reed

    Full Text Available Rift Valley fever virus (RVFV is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirin's failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential

  13. A series of abnormal climatic conditions caused the most severe outbreak of first-generation adults of the meadow moth ( Loxostege sticticalis L.) in China

    Science.gov (United States)

    Chen, Xiao; Zeng, Juan; Zhai, Baoping

    2016-06-01

    The meadow moth, Loxostege sticticalis L., is a destructive migratory pest in the northern temperate zone. The outbreak mechanism of first-generation adults in China remains unclear. In 2008, the density of first-generation larvae was very low or even negligible in most sites in China. However, a great number of first-generation adults appeared unexpectedly in late July, and their offspring caused the most severe infestation on record. The present study aims to determine where the large influx of immigrant adults originated from and how this unprecedented population was established. Source areas were explored by trajectory analysis, and climatic patterns related to the population increase were investigated. Results showed that the outbreak population mainly immigrated from Northeast Mongolia and the Chita State of Russia, and the buildup of such a large population could be attributed to an exceptional northward migration of overwintered adults from North China to East Mongolia in the spring of 2007 and unusually favourable climatic conditions in the next two growth seasons. These results indicated that the population dynamics of meadow moth in Northeast Asia would be difficult to predict when only considering local climatic factors and population size within one country. International joint monitoring and information sharing related to this pest between China, Mongolia and Russia should be implemented.

  14. Case report of a family with benign familial neutropenia and the implications for the general dental practitioner.

    Science.gov (United States)

    Casey, Christine; Brooke, Tony; Davies, Rebecca; Franklin, Deborah

    2011-03-01

    Benign familial neutropenia (BFN) is a condition where there is a decrease in circulating neutrophils in the blood and patients suffer from oral manifestations which include: persistant periodontal disease, recurrent neutropenic ulceration and candidal infections. This report discusses a family affected by BFN and the effects on their oral health. Benign familial neutropenia is a rare condition and this article aims to raise awareness among general dental practitioners so that prompt referral and management in secondary care can be arranged.

  15. Severe Psychological Distress of Evacuees in Evacuation Zone Caused by the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey.

    Science.gov (United States)

    Kunii, Yasuto; Suzuki, Yuriko; Shiga, Tetsuya; Yabe, Hirooki; Yasumura, Seiji; Maeda, Masaharu; Niwa, Shin-Ichi; Otsuru, Akira; Mashiko, Hirobumi; Abe, Masafumi

    2016-01-01

    Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey. We measured mental health status using the Kessler 6-item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores ≥13 and ≤12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models. The median K6 score was 5 (interquartile range: 1-10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002). The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by increased risk perception. To provide

  16. Overexpression of AtDREB1A causes a severe dwarf phenotype by decreasing endogenous gibberellin levels in soybean [Glycine max (L. Merr].

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    Haicui Suo

    Full Text Available Gibberellic acids (GAs are plant hormones that play fundamental roles in plant growth and developmental processes. Previous studies have demonstrated that three key enzymes of GA20ox, GA3ox, and GA2ox are involved in GA biosynthesis. In this study, the Arabidopsis DREB1A gene driven by the CaMV 35S promoter was introduced into soybean plants by Agrobacterium- mediated transformation. The results showed that the transgenic soybean plants exhibited a typical phenotype of GA-deficient mutants, such as severe dwarfism, small and dark-green leaves, and late flowering compared to those of the non-transgenic plants. The dwarfism phenotype was rescued by the application of exogenous GA(3 once a week for three weeks with the concentrations of 144 µM or three times in one week with the concentrations of 60 µM. Quantitative RT-PCR analysis revealed that the transcription levels of the GA synthase genes were higher in the transgenic soybean plants than those in controls, whereas GA-deactivated genes except GmGA2ox4 showed lower levels of expression. The transcript level of GmGA2ox4 encoding the only deactivation enzyme using C(20-GAs as the substrates in soybean was dramatically enhanced in transgenic plants compared to that of wide type. Furthermore, the contents of endogenous bioactive GAs were significantly decreased in transgenic plants than those of wide type. The results suggested that AtDREB1A could cause dwarfism mediated by GA biosynthesis pathway in soybean.

  17. Overexpression of AtDREB1A causes a severe dwarf phenotype by decreasing endogenous gibberellin levels in soybean [Glycine max (L.) Merr].

    Science.gov (United States)

    Suo, Haicui; Ma, Qibin; Ye, Kaixin; Yang, Cunyi; Tang, Yujuan; Hao, Juan; Zhang, Zhanyuan J; Chen, Mingluan; Feng, Yuqi; Nian, Hai

    2012-01-01

    Gibberellic acids (GAs) are plant hormones that play fundamental roles in plant growth and developmental processes. Previous studies have demonstrated that three key enzymes of GA20ox, GA3ox, and GA2ox are involved in GA biosynthesis. In this study, the Arabidopsis DREB1A gene driven by the CaMV 35S promoter was introduced into soybean plants by Agrobacterium- mediated transformation. The results showed that the transgenic soybean plants exhibited a typical phenotype of GA-deficient mutants, such as severe dwarfism, small and dark-green leaves, and late flowering compared to those of the non-transgenic plants. The dwarfism phenotype was rescued by the application of exogenous GA(3) once a week for three weeks with the concentrations of 144 µM or three times in one week with the concentrations of 60 µM. Quantitative RT-PCR analysis revealed that the transcription levels of the GA synthase genes were higher in the transgenic soybean plants than those in controls, whereas GA-deactivated genes except GmGA2ox4 showed lower levels of expression. The transcript level of GmGA2ox4 encoding the only deactivation enzyme using C(20)-GAs as the substrates in soybean was dramatically enhanced in transgenic plants compared to that of wide type. Furthermore, the contents of endogenous bioactive GAs were significantly decreased in transgenic plants than those of wide type. The results suggested that AtDREB1A could cause dwarfism mediated by GA biosynthesis pathway in soybean.

  18. Exposure to severe stressors causes long-lasting dysregulation of resting and stress-induced activation of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Belda, Xavier; Rotllant, David; Fuentes, Silvia; Delgado, Raúl; Nadal, Roser; Armario, Antonio

    2008-12-01

    Exposure to some predominantly emotional (electric shock) and systemic (interleukin-1beta) stressors has been found to induce long-term sensitization of the hypothalamic-pituitary-adrenal (HPA) responsiveness to further superimposed stressors. Since exposure to immobilization on wooden boards (IMO) is a severe stressor and may have interest regarding putative animal models of post-traumatic stress disorders (PTSD), we have characterized long-lasting effects of a single exposure to IMO and other stressors on the HPA response to the same (homotypic) and to novel (heterotypic) stressors and the putative mechanisms involved. A single exposure to IMO caused a long-lasting reduction of peripheral and central responses of the HPA axis, likely to be mediated by some brain areas, such as the lateral septum and the medial amygdala. This desensitization is not explained by changes in negative glucocorticoid feedback, and, surprisingly, it is positively related to the intensity of the stressors. In contrast, the HPA response to heterotypic stressors (novel environments) was enhanced, with maximal sensitization on the day after IMO. Sensitization progressively vanished over the course of 1-2 weeks and was not modulated by IMO-induced corticosterone release. Moreover, it could not be explained by changes in the sensitivity of the HPA axis to fast or intermediate/delayed negative feedback, as evaluated 1 week after exposure to IMO, using shock as the heterotypic stressor. Long-lasting stress-induced behavioral changes reminiscent of enhanced anxiety and HPA sensitization are likely to be parallel but partially independent phenomena, the former being apparently not related to the intensity of stressors.

  19. The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report

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    Sergio Matarasso

    2009-01-01

    Full Text Available Cyclic Neutropenia (CN is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC was ≥500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth (PD≤4 mm and an improvement of the oral hygiene conditions recorded at 6-month follow-up.

  20. Managing febrile neutropenia in adult cancer patients: an integrative review of the literature

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    Juliana Nunes Ferreira

    Full Text Available ABSTRACT Objective: To analyze the interventions performed by health professionals with a view to managing chemotherapy-induced febrile neutropenia. Method: Integrative literature review, the sample of 12 primary articles was selected from the following databases: LILACS, SciELO, BVS, PubMed, CINAHL and Web of Science. Results: There was a prevalence of studies, realized by doctors, focused on pharmacological treatment and on the association of methods for greater diagnostic accuracy of febrile neutropenia. A study was found on pharmaceutical management regarding antibiotic dosing efficacy and a study indicating that nurses could contribute to the identification of elderly patients who would benefit from prophylactic use of growth factor. Conclusion: There was a shortage of studies involving the participation of other health professionals, besides the doctors, and a knowledge gap regarding interprofessional practice in the management of interventions specific to their area of specialism, joint interventions and non-pharmacological interventions.

  1. Expression of fra(10)(q25) in peripheral blood and bone marrow in familial neutropenia.

    OpenAIRE

    Holmes, J A; Thompson, P W

    1988-01-01

    We report on the expression of fra(10)(q25) in a mother and daughter with familial chronic neutropenia. Differences in expression of the fragile site in bone marrow cells compared with peripheral blood lymphocytes were observed. Short term bone marrow cultures in complete medium showed high levels of spontaneous expression, whereas in 72 hour stimulated blood cultures it was virtually absent. There were also differences in the types of lesions found; chromosome type lesions predominated in th...

  2. Canadian supportive care recommendations for the management of neutropenia in patients with cancer

    OpenAIRE

    Kouroukis, C.T.; Chia, S.; Verma, S.; Robson, D.; Desbiens, C.; Cripps, C.; Mikhael, J.

    2008-01-01

    Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest...

  3. Impact of chemotherapy-induced neutropenia on quality of life: a prospective pilot investigation.

    Science.gov (United States)

    Fortner, Barry V; Schwartzberg, Lee; Tauer, Kurt; Houts, Arthur C; Hackett, James; Stolshek, Brad S

    2005-07-01

    In this exploratory, prospective study evaluated quality of life (QoL) changes in patients with diverse cancers during the first cycle of myelosuppressive chemotherapy. Of 80 patients enrolled, 71 were observed during one of five chemotherapy regimens: docetaxel; CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); carboplatin-paclitaxel; carboplatin-docetaxel; and carboplatin-gemcitabine. Complete blood counts were taken weekly. QoL and symptom burden measures were administered at baseline and throughout the cycle, and included SF-36, Cancer Care Monitor (CCM), Hospital Anxiety and Depression Scale (HADS), and Psychosocial Adjustment to Illness Scale (PAIS). Using generalized estimating equations, we modeled the change in each measure from baseline to the end of each week using the following covariates: baseline QoL measure, baseline SF-36 Physical and Mental Health Summary scores, sex, age, cycle week, grade 4 neutropenia any time in the past 7 days (yes/no), and the interaction of the latter two covariates. Of the 71 patients observed, 33 developed grade 4 neutropenia during the first 2 weeks. Changes from baseline in SF-36 Bodily Pain, HADS Anxiety, and PAIS Social Environment scores were significantly less favorable (P<0.05) when patients experienced grade 4 neutropenia any time in the past 7 days compared to when they did not (grade 0-3). A similar, but non-significant, trend was also observed for 12 other QoL measures. QoL may be adversely affected up to 7 days after patients experience grade 4 (versus grade 0-3) neutropenia. Such findings need to be examined further in studies with adequate statistical power to test a priori hypotheses regarding specific QoL measures.

  4. A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

    Science.gov (United States)

    Tamary, H; Yaniv, I; Stein, J; Dgany, O; Shalev, Z; Shechter, T; Resnitzky, P; Shaft, D; Zoldan, M; Kornreich, L; Levy, R; Cohen, A; Moser, R A; Kapelushnik, J; Shalev, H

    2003-09-01

    Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

  5. Alloimmune neonatal neutropenia in Croatia during the 1998-2008 period.

    Science.gov (United States)

    Tomicic, Maja; Starcevic, Mirta; Ribicic, Rebeka; Golubic-Cepulic, Branka; Hundric-Haspl, Zeljka; Jukic, Irena

    2014-05-01

    The aim of this study was to estimate the incidence of the disease and to analyze laboratory data of 23 newborns undergoing serologic testing for alloimmune neonatal neutropenia (ANN) during the 1998-2008 period in Croatia. Laboratory data on 23 newborns undergoing serologic testing for ANN during the 1998-2008 period and epidemiologic data on the number of live births in Croatia were analyzed. Laboratory testing for ANN included serologic screening of maternal and neonatal sera and granulocytes (neutrophils) by immunofluorescence (IF) method. The monoclonal antibody immobilization of neutrophil antigens (MAINA) was employed to determine anti-HNA antibody specificity. Anti-HNA antibodies were detected in seven (54%) of 13 cases of serologically positive ANN. Only anti-HLA class I antibodies were demonstrated in four (31%) of 13 cases In the 2007-2008 period of prospective data collection, the number of serologically verified ANN cases was one case per 17,323 live births. Results of the prospective study conducted at Maternity Ward, Department of Gynecology and Obstetrics, Sestre milosrdnice University Hospital Center yielded the ANN incidence of one case per 2843 live births. Monitoring of neutrophil count in neonatal blood and serologic testing for ANN in case of isolated neutropenia in the newborn contributed considerably to timely detection of ANN. Neonatal alloimmune neutropenia-incidence, serologic diagnosis, antineutrophil antibodies, anti-HNA, anti-HLA class I, Croatia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Neutropenia and eosinophilia among Ethiopian immigrants to Israel: Familial or environmental?

    Science.gov (United States)

    Tandeter, Howard; Glick, Karina; Moser, Asher

    2016-12-01

    Due to trends of population movements, Israeli family physicians are treating increasing numbers of African immigrants from Ethiopia. These immigrants were found to have complete blood counts (CBC) that are different from other ethnic groups, with a higher prevalence of eosinophilia and neutropenia. To evaluate haematological findings in an attempt to define whether they behave as familial (genetic) or environmental. Retrospective chart review of 300 patients from a primary care clinic: 100 individuals of Ethiopian heritage born in Ethiopia (EE); 100 individuals of Ethiopian heritage born in Israel, whose parents were born in Ethiopia (EI), and a control group of 100 patients who were not of Ethiopian heritage (C). Absolute eosinophilia (greater than 500/dl) was found in 13% of the EE study group significantly higher than the two other groups (P neutropenia (defined as less than 1500/dl) was found in 32% of EE group, 20% of EI, and 1% of C (P familial-genetic nature is probably the reason for the higher prevalence of neutropenia in this population, although some environmental influence may play a role. The knowledge of these findings may be useful for physicians treating people migrating from Africa.

  7. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa.

    Science.gov (United States)

    Hartel, Bas P; Löfgren, Maria; Huygen, Patrick L M; Guchelaar, Iris; Lo-A-Njoe Kort, Nicole; Sadeghi, Andre M; van Wijk, Erwin; Tranebjærg, Lisbeth; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Möller, Claes; Pennings, Ronald J E

    2016-09-01

    Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Síndrome diencéfalico como causa de desnutrición severa Diencephalic syndrome as a cause of severe malnutrition

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    Leonor Báez Segurola

    2013-03-01

    Full Text Available El síndrome diencefálico es un complejo de síntomas y signos causados por disfunción de esta área del encéfalo caracterizado por una marcada desnutrición aun cuando la ingesta calórica es normal. Se presentan dos casos, el primero de ellos una niña de 13 meses de edad con antecedentes de un fallo de medro a partir del tercer mes de vida, que ingresó en este servicio para el estudio de una desnutrición proteico energética severa que presentó en el transcurso de su evolución un apetito inestable y al mes de ingresada un evento paroxístico. Se le realizó resonancia magnética nuclear y se comprobó imagen hipodensa, redondeada, que medía aproximadamente 3 x 3 cm en región supraselar; fue intervenida quirúrgicamente en 2 ocasiones, se realizó exéresis del tumor, y se confirmó anatomopatológicamente un astrocitoma pilocítico de bajo grado. El segundo paciente, un lactante que ingresó con el diagnóstico confirmado de tumor intracraneal para estudio, semejante al caso presentado anteriormente, mostraba una marcada desnutrición proteico energética, se le realizó tomografía axial computarizada en la que se pudo apreciar una extensa masa tumoral supraselar con dilatación del sistema ventricular. Durante su evolución presentó marcada anorexia con pérdida de peso progresiva, por lo que se realizó gastrostomía. A los 59 días falleció como consecuencia de una pancitopenia, y la necropsia concluyó: astrocitoma pilocítico de bajo grado.Diencephalic syndrome is a set of symptoms and signs caused by dysfunction in this area of the encephalon and characterized by marked malnutrition despite adequate intake of calories. Two cases were reported in this paper. The first one was a 13-years old girl with a history of medro failure since her 3rd month of life, who was admitted to this service for the study of her severe protein/energy malnutrition. In the course of her hospitalization, she presented with unstable appetite and

  9. Coinheritance of biallelic SLURP1 and SLC39A4 mutations cause a severe genodermatosis with skin peeling and hair loss all over the body.

    Science.gov (United States)

    Harms, F L; Nampoothiri, S; Kortüm, F; Thomas, J; Panicker, V V; Alawi, M; Altmüller, J; Yesodharan, D; Kutsche, K

    2018-06-27

    Next-generation sequencing (NGS), especially multi-gene panels and whole-exome sequencing (WES), is a tool for identifying the cause of monogenic disorders and has played a role in uncovering the genetic cause of previously uncharacterized genodermatoses. 1 By the application of NGS, the concept of apparently novel or atypical clinical presentations has been challenged by the finding of two or more genetic diagnoses in affected individuals. Approximately 5% of cases in which WES was informative had dual or multiple molecular diagnoses. 2 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

    Directory of Open Access Journals (Sweden)

    Miguel E. Pinto

    2012-06-01

    Full Text Available Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf. After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

  11. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

    NARCIS (Netherlands)

    Hartel, B.P.; Lofgren, M.; Huygen, P.L.; Guchelaar, I.; Lo, A.N.K.N.; Sadeghi, A.M.; van Wijk, E.; Tranebjaerg, L.; Kremer, H.; Kimberling, W.J.; Cremers, C.W.R.J.; Moller, C.; Pennings, R.J.

    2016-01-01

    OBJECTIVES: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates

  12. Hypophosphatemia is a common complication in severely disabled individuals with neurological disorders and is caused by infection, refeeding and Fanconi syndrome.

    Science.gov (United States)

    Saito, Yoshiaki; Aoki, Yusuke; Takeshita, Eri; Saito, Takashi; Sugai, Kenji; Komaki, Hirofumi; Nakagawa, Eiji; Ishiyama, Akihiko; Takanoha, Satoko; Wada, Satoru; Sasaki, Masayuki

    2014-11-01

    To describe the characteristics of hypophosphatemia in severely disabled individuals with neurological disorders and to identify its causative factors. We retrospectively reviewed clinical data from 82 individuals with motor skills classified as sitting, rollover or bedridden. Age, gender and body mass index were compared in individuals with (n=19) and without (n=63) a history of hypophosphatemia (serum phosphate levels refeeding syndrome (n=4) and Fanconi syndrome (n=3), but was unidentifiable in one episode. Significant elevations in C-reactive protein levels and reductions in sodium levels were observed during hypophosphatemia episodes. Hypophosphatemia is a common complication in severely disabled individuals with frequent bacterial infections, refeeding following malnutrition and valproate administration for epilepsy treatment. Because severe hypophosphatemia is life threatening, serum phosphate levels should be closely monitored in this population. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Inter-Ethnic Differences in Quantified Coronary Artery Disease Severity and All-Cause Mortality among Dutch and Singaporean Percutaneous Coronary Intervention Patients

    NARCIS (Netherlands)

    Gijsberts, Crystel M; Seneviratna, Aruni; Höfer, IE; Agostoni, Pierfrancesco; Rittersma, Saskia Z. H.; Pasterkamp, Gerard; Hartman, Mikael; Pinto de Carvalho, Leonardo; Richards, A Mark; Asselbergs, Folkert W; de Kleijn, Dominique P V; Chan, Mark Y

    2015-01-01

    BACKGROUND: Coronary artery disease (CAD) is a global problem with increasing incidence in Asia. Prior studies reported inter-ethnic differences in the prevalence of CAD rather than the severity of CAD. The angiographic "synergy between percutaneous coronary intervention (PCI) with taxus and cardiac

  14. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    OpenAIRE

    Valeria Contreras; Sebastián Sepúlveda; Ana Heredia

    2016-01-01

    En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta p...

  15. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    Science.gov (United States)

    Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

    2016-02-24

    It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity.

  16. Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay.

    Science.gov (United States)

    Onodera, Rie; Kurita, Emi; Taniguchi, Kikuyo; Karakawa, Shuhei; Okada, Satoshi; Kihara, Hirotaka; Fujii, Teruhisa; Kobayashi, Masao

    2017-11-01

    Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed. We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA. The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody. EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. © 2017 AABB.

  17. The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

    NARCIS (Netherlands)

    Miedema, Karin G. E.; de Bont, Eveline S. J. M.; Elferink, Rob F. M. Oude; van Vliet, Michel J.; Nijhuis, Claudi S. M. Oude; Kamps, Willem A.; Tissing, Wim J. E.

    2011-01-01

    In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced

  18. Poliartritis y tenosinovitis grave por Streptococcus agalactiae en un paciente con hipoesplenia funcional Severe polyarthritis and tenosynovitis caused by Streptococcus agalactiae in a patient with functional hyposplenia

    Directory of Open Access Journals (Sweden)

    Domingo C. Balderramo

    2002-08-01

    Full Text Available La artritis por Streptococcus agalactiae es infrecuente. No conocemos publicaciones de casos sobre la afección tendinosa por este microorganismo. Se presenta una mujer de 46 años que consultó por fiebre, poliartralgias, mialgias, diarrea y vómitos. Como antecedentes presentaba carcinoma papilar de tiroides e hipoesplenia funcional. Al examen se encontraba hemodinámicamente inestable, febril, con artritis de mano izquierda, muñecas, codos, hombro derecho y tobillo izquierdo. Presentaba tenosinovitis en ambos pies y en la mano izquierda. Los hemocultivos y el cultivo de la bursa olecraniana derecha fueron positivos para S. agalactiae. La ecografía mostró signos de tenosinovitis del tibial anterior izquierdo. Completó 20 días de tratamiento endovenoso con cefazolina y 12 días de cefuroxima oral. El cuadro articular revirtió completamente en 60 días. El Streptococcus agalactiae puede causar, en forma infrecuente, un síndrome de poliartritis, tenosinovitis y fiebre similar al producido por la infección gonocócica.Cases of arthritis caused by Streptococcus agalactiae are infrequent and in our knowledge there are no case reports of tenosynovitis caused by S. agalactiae. A 46-year-old woman presented with fever, polyarthralgia, myalgia, diarrhea and vomiting. She had a history of papillary thyroid carcinoma and functional hyposplenia. She was febrile, with arthritis in hands, wrists, elbows, right shoulder and left ankle joints, and presented tenosynovitis in both feet and left hand. Blood and right olecranon bursa sample cultures were positive for S. agalactiae. An ultrasound scan made at the musculus tibialis anterior of left foot revealed signs of tenosynovitis. She was treated with intravenous cefazolin for 20 days and oral cefuroxime for 12 days. The joint involvement completely subsided in 60 days. Streptococcus agalactiae can cause, infrequently, a polyarthritis and tenosynovitis syndrome similar to disseminated gonococcal

  19. Sustained oxidative stress causes late acute renal failure via duplex regulation on p38 MAPK and Akt phosphorylation in severely burned rats.

    Directory of Open Access Journals (Sweden)

    Yafei Feng

    Full Text Available BACKGROUND: Clinical evidence indicates that late acute renal failure (ARF predicts high mortality in severely burned patients but the pathophysiology of late ARF remains undefined. This study was designed to test the hypothesis that sustained reactive oxygen species (ROS induced late ARF in a severely burned rat model and to investigate the signaling mechanisms involved. MATERIALS AND METHODS: Rats were exposed to 100°C bath for 15 s to induce severe burn injury (40% of total body surface area. Renal function, ROS generation, tubular necrosis and apoptosis, and phosphorylation of MAPK and Akt were measured during 72 hours after burn. RESULTS: Renal function as assessed by serum creatinine and blood urea nitrogen deteriorated significantly at 3 h after burn, alleviated at 6 h but worsened at 48 h and 72 h, indicating a late ARF was induced. Apoptotic cells and cleavage caspase-3 in the kidney went up slowly and turned into significant at 48 h and 72 h. Tubular cell ROS production shot up at 6 h and continuously rose during the 72-h experiment. Scavenging ROS with tempol markedly attenuated tubular apoptosis and renal dysfunction at 72 h after burn. Interestingly, renal p38 MAPK phosphorylation elevated in a time dependent manner whereas Akt phosphorylation increased during the first 24 h but decreased at 48 h after burn. The p38 MAPK specific inhibitor SB203580 alleviated whereas Akt inhibitor exacerbated burn-induced tubular apoptosis and renal dysfunction. Furthermore, tempol treatment exerted a duplex regulation through inhibiting p38 MAPK phosphorylation but further increasing Akt phosphorylation at 72 h postburn. CONCLUSIONS: These results demonstrate that sustained renal ROS overproduction induces continuous tubular cell apoptosis and thus a late ARF at 72 h after burn in severely burned rats, which may result from ROS-mediated activation of p38 MAPK but a late inhibition of Akt phosphorylation.

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

    Science.gov (United States)

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

    2009-10-01

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

  1. LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

    Science.gov (United States)

    Nocoń-Bohusz, Julita; Wikiera, Beata; Basiak, Aleksander; Śmigiel, Robert; Noczyńska, Anna

    2016-02-18

    Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed. © Polish Society for Pediatric Endocrinology and Diabetology.

  2. CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.

    Science.gov (United States)

    Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina

    2016-12-01

    Cyclin-dependent kinase-like 5 ( CDKL5 ) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future. Georg Thieme Verlag KG Stuttgart · New York.

  3. JPH3 Repeat Expansions Cause a Progressive Akinetic-Rigid Syndrome with Severe Dementia and Putaminal Rim in a Five-Generation African-American Family

    Science.gov (United States)

    Schneider, Susanne A.; Marshall, Kate E.; Xiao, Jianfeng; LeDoux, Mark S.

    2012-01-01

    We report the clinical, neuropsychological, genetic and radiological features of a large five-generation African-American kindred from the southern United States presenting with a progressive akinetic-rigid syndrome and severe dementia, but clinically insignificant chorea, due to mutations in JPH3. Overt disease onset was in the mid-twenties to late thirties with cognitive decline, REM sleep disturbance or psychiatric features, followed by development of a levodopa-unresponsive akinetic-rigid motor syndrome. Dystonia and myoclonus were present in some subjects. A bedridden, non-verbal severely akinetic-rigid state developed within 10 to 15 years after onset. CTG repeat expansions ranged from 47 to 53. Imaging revealed generalized cerebral atrophy with severe striatal involvement and putaminal rim hyperintensity. Analysis of our kindred indicates that JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. Moreover, chorea may not be overtly manifest at presentation or during significant parts of the disease course. PMID:22447335

  4. The Effect of Sharrows, Painted Bicycle Lanes and Physically Protected Paths on the Severity of Bicycle Injuries Caused by Motor Vehicles.

    Science.gov (United States)

    Wall, Stephen P; Lee, David C; Frangos, Spiros G; Sethi, Monica; Heyer, Jessica H; Ayoung-Chee, Patricia; DiMaggio, Charles J

    2016-01-01

    We conducted individual and ecologic analyses of prospectively collected data from 839 injured bicyclists who collided with motorized vehicles and presented to Bellevue Hospital, an urban Level-1 trauma center in New York City, from December 2008 to August 2014. Variables included demographics, scene information, rider behaviors, bicycle route availability, and whether the collision occurred before the road segment was converted to a bicycle route. We used negative binomial modeling to assess the risk of injury occurrence following bicycle path or lane implementation. We dichotomized U.S. National Trauma Data Bank Injury Severity Scores (ISS) into none/mild (0-8) versus moderate, severe, or critical (>8) and used adjusted multivariable logistic regression to model the association of ISS with collision proximity to sharrows (i.e., bicycle lanes designated for sharing with cars), painted bicycle lanes, or physically protected paths. Negative binomial modeling of monthly counts, while adjusting for pedestrian activity, revealed that physically protected paths were associated with 23% fewer injuries. Painted bicycle lanes reduced injury risk by nearly 90% (IDR 0.09, 95% CI 0.02-0.33). Holding all else equal, compared to no bicycle route, a bicycle injury nearby sharrows was nearly twice as likely to be moderate, severe, or critical (adjusted odds ratio 1.94; 95% confidence interval (CI) 0.91-4.15). Painted bicycle lanes and physically protected paths were 1.52 (95% CI 0.85-2.71) and 1.66 (95% CI 0.85-3.22) times as likely to be associated with more than mild injury respectively.

  5. The Effect of Sharrows, Painted Bicycle Lanes and Physically Protected Paths on the Severity of Bicycle Injuries Caused by Motor Vehicles

    Directory of Open Access Journals (Sweden)

    Stephen P. Wall

    2016-12-01

    Full Text Available We conducted individual and ecologic analyses of prospectively collected data from 839 injured bicyclists who collided with motorized vehicles and presented to Bellevue Hospital, an urban Level-1 trauma center in New York City, from December 2008 to August 2014. Variables included demographics, scene information, rider behaviors, bicycle route availability, and whether the collision occurred before the road segment was converted to a bicycle route. We used negative binomial modeling to assess the risk of injury occurrence following bicycle path or lane implementation. We dichotomized U.S. National Trauma Data Bank Injury Severity Scores (ISS into none/mild (0–8 versus moderate, severe, or critical (>8 and used adjusted multivariable logistic regression to model the association of ISS with collision proximity to sharrows (i.e., bicycle lanes designated for sharing with cars, painted bicycle lanes, or physically protected paths. Negative binomial modeling of monthly counts, while adjusting for pedestrian activity, revealed that physically protected paths were associated with 23% fewer injuries. Painted bicycle lanes reduced injury risk by nearly 90% (IDR 0.09, 95% CI 0.02–0.33. Holding all else equal, compared to no bicycle route, a bicycle injury nearby sharrows was nearly twice as likely to be moderate, severe, or critical (adjusted odds ratio 1.94; 95% confidence interval (CI 0.91–4.15. Painted bicycle lanes and physically protected paths were 1.52 (95% CI 0.85–2.71 and 1.66 (95% CI 0.85–3.22 times as likely to be associated with more than mild injury respectively.

  6. Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency

    DEFF Research Database (Denmark)

    McElvaney, Noel G; Burdon, Jonathan; Holmes, Mark

    2017-01-01

    BACKGROUND: Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect...... of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. METHODS: Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open...

  7. T−B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3ζ subunit of the T-cell antigen receptor complex

    OpenAIRE

    Roberts, Joseph L.; Lauritsen, Jens Peter H.; Cooney, Myriah; Parrott, Roberta E.; Sajaroff, Elisa O.; Win, Chan M.; Keller, Michael D.; Carpenter, Jeffery H.; Carabana, Juan; Krangel, Michael S.; Sarzotti, Marcella; Zhong, Xiao-Ping; Wiest, David L.; Buckley, Rebecca H.

    2007-01-01

    CD3ζ is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T−B+NK+ severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3ζ gene. The few T cells present contained no detectable CD3ζ protein, expressed low levels of cell surface CD3ε, and were nonfunctional. CD4+CD8−CD...

  8. Report of 15 injuries caused by lionfish (pterois volitans) in aquarists in Brazil: a critical assessment of the severity of envenomations.

    Science.gov (United States)

    Haddad, Vidal; Stolf, Hamilton Ometto; Risk, José Yamin; França, Francisco Os; Cardoso, João Luiz Costa

    2015-01-01

    Lionfish are venomous fish that belong to the Scorpaenidae family. Individuals of this family and those of the Synanceiidae family comprise most of the existing venomous fish in the world. Lionfish are originally found in the Indo-Pacific, but they have received special attention in the last years for their dissemination in the Atlantic Ocean, with the emergence of large populations in the USA, Caribbean and South America. Because of its beauty, this fish has always been present in private and commercial aquariums around the world. Herein, we describe 15 envenomations in aquarists registered in a period of eighteen years (1997-2014). The stings caused excruciating pain and marked inflammation, with local erythema, edema, heat, paleness and cyanosis. In one case, it was possible to observe vesicles and blisters. There were no skin necroses or marked systemic manifestations. We discuss the possible coming of the fish to South America and the circumstances and clinical impact of the envenomations.

  9. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

    DEFF Research Database (Denmark)

    Hartel, Bas P.; Lofgren, Maria; Huygen, Patrick L. M.

    2016-01-01

    Objectives Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates...... the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. Design...... A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA...

  10. Analisi Costo-Efficacia di Amfotericina B Liposomiale (L-AmB versus Amfotericina B Complesso Lipidico (ABLC nel trattamento empirico della neutropenia febbrile

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2005-12-01

    Full Text Available Current international guidelines for the management of immuno-compromised patients with febrile neutropenia recommend a systemic antimicrobial therapy if fever hasn’t receded after three days of antibiotic treatment. Amphotericin B remains the gold standard because of its broad spectrum fungicidal action and minimal resistance development risk. Nonetheless, therapeutic use of the standard formulation, Amphotericin B deoxycholate, is limited by its toxicity, especially on the kidneys. To counteract this, amphotericin B has been encapsulated in liposomes, a process which reduces its toxicity and allows higher doses to be given. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD, amB lipid complex (ABLC, and liposomal amB (L-AmB. These lipid formulations differ in pharmacodynamics and pharmacokinetics, and can’t therefore be considered interchangeable. Besides, they are more expensive than Amphotericin B deoxycholate. Aim of the study is to perform a cost/effectiveness analysis (CEA comparing L-AmB (3mg/kg/die or 5mg/kg/ die and ABLC (5mg/kg/die as first-line antimicrobial empirical treatments in immuno-compromised patients with febrile neutropenia resistant to broad spectrum antibiotics. Secondly, we present a cost-minimization analysis (CMA of the considered alternatives, assuming the same efficacy for all treatments. At the end we value the principal cost items from the point of view of the Italian Health Service, with a particular focus on the economic burden caused by adverse reactions.

  11. O papel da neutropenia no prognóstico do doente oncológico com pneumonia adquirida na comunidade The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Fátima Caeiro

    2009-08-01

    Full Text Available A doença infecciosa contribui para uma elevada morbilidade e mortalidade no doente oncológico, representando a pneumonia adquirida na comunidade a mais frequente. O desenvolvimento de PAC no doente neoplásico parece advir da modificação de mecanismos de defesa imunitária resultante, quer da patologia maligna, quer do tratamento oncológico. O risco de infecção relacionada com o tipo de neoplasia pode associar-se ao défice de imunidade humoral, celular ou do número de neutrófilos. As doenças hematológicas malignas podem predispor o doente às infecções devido à substituição da medula por células neoplásicas. Consequentemente, estes doentes têm neutropenia funcional, apesar de apresentarem, muitas vezes, um número normal ou aumentado de neutrófilos. Por outro lado, estes doentes podem ter neutropenia como efeito secundário da quimioterapia e/ou radioterapia (neutropenia absoluta. A gravidade da neutropenia foi considerada como principal factor de risco isolado no doente neoplásico, com particular relevância se o número de neutrófilos ≤500cel/mm³. A mortalidade global atribuída à neutropenia febril no doente neoplásico é de 30-50%. Nas últimas décadas, o tratamento das infecções na população oncológica foi direccionado, primariamente, para o manuseamento da neutropenia febril, devido ao facto de o local da infecção não ser determinado em 50-80% dos casos. As guidelines da American Thoracic Society de 2001 utilizavam a neutropenia para identificar os quadros mais graves de PAC nos doentes oncológicos. Os doen tes com patologia hematológica e neutropenia funcional ou indivíduos com qualquer tipo de neoplasia e neutropenia absoluta foram excluídos das referidas guidelines. A decisão de incluir doentes com tumores sólidos não neutropénicos foi baseada, apenas, na opinião de especialistas. Assim, os clínicos podiam sentir-se confiantes e tratar a PAC no doente oncológico não neutropénico como na

  12. A convenient model of severe, high incidence autoimmune gastritis caused by polyclonal effector T cells and without perturbation of regulatory T cells.

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    Eric Tu

    Full Text Available Autoimmune gastritis results from the breakdown of T cell tolerance to the gastric H(+/K(+ ATPase. The gastric H(+/K(+ ATPase is responsible for the acidification of gastric juice and consists of an α subunit (H/Kα and a β subunit (H/Kβ. Here we show that CD4(+ T cells from H/Kα-deficient mice (H/Kα(-/- are highly pathogenic and autoimmune gastritis can be induced in sublethally irradiated wildtype mice by adoptive transfer of unfractionated CD4(+ T cells from H/Kα(-/- mice. All recipient mice consistently developed the most severe form of autoimmune gastritis 8 weeks after the transfer, featuring hypertrophy of the gastric mucosa, complete depletion of the parietal and zymogenic cells, and presence of autoantibodies to H(+/K(+ ATPase in the serum. Furthermore, we demonstrated that the disease significantly affected stomach weight and stomach pH of recipient mice. Depletion of parietal cells in this disease model required the presence of both H/Kα and H/Kβ since transfer of H/Kα(-/- CD4(+ T cells did not result in depletion of parietal cells in H/Kα(-/- or H/Kβ(-/- recipient mice. The consistency of disease severity, the use of polyclonal T cells and a specific T cell response to the gastric autoantigen make this an ideal disease model for the study of many aspects of organ-specific autoimmunity including prevention and treatment of the disease.

  13. The use of stable xenon-enhanced computed tomographic studies of cerebral blood flow to define changes in cerebral carbon dioxide vasoresponsivity caused by a severe head injury.

    Science.gov (United States)

    Marion, D W; Bouma, G J

    1991-12-01

    Previous studies using the xenon-133 cerebral blood flow (CBF) method have documented the impairment of CO2 vasoresponsivity after a severe head injury, but only global values can be obtained reliably with this technique. We studied CO2 vasoresponsivity using the stable xenon-enhanced computed tomographic CBF method, which provided information about well-defined cortical regions and deep brain structures not available with the xenon-133 method. In 17 patients with admission Glasgow Coma Scale scores of 8 or less, hemispheric CO2 vasoresponsivity ranged from 1.3 to 8.5% per mm Hg change in partial CO2 pressure. Lobar, cerebellar, basal ganglia, and brain stem CO2 vasoresponsivity frequently varied from the mean global value by more than 25%. In all but one patient, local CO2 vasoresponsivity in one or more of these areas differed from the mean global value by more than 50%. The greatest variability occurred in patients with acute subdural hematomas and diffuse (bihemispheric) injuries. This variability in CO2 vasoresponsivity has important implications for the effective and safe management of intracranial hypertension that frequently accompanies severe head injury.

  14. Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility.

    Science.gov (United States)

    Haghighi, Amirreza; Haghighi, Alireza; Setoodeh, Aria; Saleh-Gohari, Nasrollah; Astuti, Dewi; Barrett, Timothy G

    2013-03-01

    Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G>A (p.Asp211Asn) in exon 5, and family 2: c.1456C>T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families.

  15. Prophylaxis against febrile neutropenia with pegfilgrastim in Italy: a budget impact analysis

    Directory of Open Access Journals (Sweden)

    Giovanni Rosti

    2011-09-01

    Full Text Available Introduction: prophylaxis with granulocyte colony-stimulating factors (G-CSF is indicated for reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy for malignancy.
Objective: to evaluate the budgetary impact for the Italian NHS.
Design: a decision-analytic model has been developed to analyze the budget impact from the national health care system perspective. Costs include direct healthcare costs to the public payer of G-CSFs as well as their administration costs and costs of FN-related events. The comparison has been done using prophylaxis with G‑CSF (filgrastim for 11 days, pegfilgrastim, lenograstim for 11 days and antibiotics.
Patients and participants: The population of interest for the analysis were patients with breast cancer in stage II and III and patients with non-Hodgkin’s lymphoma (NHL.
Main outcome measures and results: for all the three patients group (NHL, Breast II and III, and for all the chemotherapy regimens (CHOP 21 and R-CHOP 21 for NHL, AC-T, TAC and TC for Breast stage II and III the budget impact analyses shows a cost reduction for the Italian NHS, as a result of an increase of the use of pegfilgrastim.
Conclusions: in Italy, a treatment strategy including pegfilgrastim as either primary or secondary prophylaxis provides value for money.


  16. Distribution and clinical determinants of time-to-positivity of blood cultures in patients with neutropenia.

    Science.gov (United States)

    Lambregts, Merel M C; Warreman, Eva B; Bernards, Alexandra T; Veelken, Hendrik; von dem Borne, Peter A; Dekkers, Olaf M; Visser, Leo G; de Boer, Mark G

    2018-02-01

    Blood cultures (BCs) are essential in the evaluation of neutropenic fever. Modern BC systems have significantly reduced the time-to-positivity (TTP) of BC. This study explores the probability of bacteraemia when BCs have remained negative for different periods of time. All adult patients with neutropenia and bacteraemia were included (January 2012-February 2016). Predictive clinical factors for short (≤16 hours) and long (>24 hours) TTP were determined. The residual probability of bacteraemia was estimated for the scenario of negative BC 24 hours after collection. The cohort consisted of 154 patients, accounting for 190 episodes of bacteraemia. Median age of 61 years, 60.5% were male. In 123 (64.7%) episodes, BC yielded a single Gram-positive micro-organism and in 49 (25.8%) a Gram-negative micro-organism (median TTP 16.7, 14.5 hours respectively, P hours in 91.6% of episodes. Central line-associated bacteraemia was associated with long TTP. The probability of bacteraemia if BC had remained negative for 24 hours was 1%-3%. The expected TTP offers guidance in the management of patients with neutropenia and suspected bacteraemia. The knowledge of negative BC can support a change in working diagnosis, and impact clinical decisions as soon as 24 hours after BC collection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia.

    Science.gov (United States)

    Al-Badriyeh, Daoud; Liew, Danny; Stewart, Kay; Kong, David C M

    2012-05-01

    In two major clinical trials, voriconazole and caspofungin were recommended as alternatives to liposomal amphotericin B for empirical use in febrile neutropenia. This study investigated the health economic impact of using voriconazole vs. caspofungin in patients with febrile neutropenia. A decision analytic model was developed to measure downstream consequences of empirical antifungal therapy. Clinical outcomes measured were success, breakthrough infection, persistent base-line infection, persistent fever, premature discontinuation and death. Treatment transition probabilities and patterns were directly derived from data in two relevant randomised controlled trials. Resource use was estimated using an expert clinical panel. Cost inputs were obtained from latest Australian sources. The analysis adopted the perspective of the Australian hospital system. The use of caspofungin led to a lower expected mean cost per patient than voriconazole (AU$40,558 vs. AU$41,356), with a net cost saving of AU$798 (1.9%) per patient. Results were most sensitive to the duration of therapy and the alternative therapy used post-discontinuation. In uncertainty analysis, the cost associated with caspofungin is less than that with voriconazole in 65.5% of cases. This is the first economic evaluation of voriconazole vs. caspofungin for empirical therapy. Caspofungin appears to have a higher probability of having cost-savings than voriconazole for empirical therapy. The difference between the two medications does not seem to be statistically significant however. © 2011 Blackwell Verlag GmbH.

  18. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    Directory of Open Access Journals (Sweden)

    Valeria Contreras

    2016-03-01

    Full Text Available En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que adicionar aminoglicósidos a los betalactámicos en el tratamiento de la neutropenia febril en pacientes con cáncer aumenta la nefrotoxicidad y podría aumentar la mortalidad en comparación con la monoterapia con betalactámicos.

  19. Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia?

    Directory of Open Access Journals (Sweden)

    Erica Koch

    2016-06-01

    Full Text Available La neutropenia febril prolongada conlleva un alto riesgo de desarrollar infecciones fúngicas invasoras, por lo que habitualmente se administra terapia antifúngica empírica en estos casos. Sin embargo, esta se asocia a importantes efectos adversos, por lo que se ha propuesto como alternativa la estrategia "preemptive" o anticipada, es decir, la indicación de antifúngicos sólo ante la evidencia indirecta de infección fúngica invasora. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen doce estudios. Cuatro estudios aleatorizados evaluaron la pregunta abordada en este artículo. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si la estrategia "preemptive" tiene algún efecto sobre la mortalidad porque la certeza de la evidencia es muy baja, pero podría disminuir levemente el uso de antifúngicos en pacientes con neutropenia febril prolongada.

  20. Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes.

    Science.gov (United States)

    Yang, Bing-Bing; Savin, Michael A; Green, Michael

    2012-01-01

    Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim. Copyright © 2012 S. Karger AG, Basel.

  1. A pilot study of sensory feedback by transcutaneous electrical nerve stimulation to improve manipulation deficit caused by severe sensory loss after stroke.

    Science.gov (United States)

    Kita, Kahori; Otaka, Yohei; Takeda, Kotaro; Sakata, Sachiko; Ushiba, Junichi; Kondo, Kunitsugu; Liu, Meigen; Osu, Rieko

    2013-06-13

    Sensory disturbance is common following stroke and can exacerbate functional deficits, even in patients with relatively good motor function. In particular, loss of appropriate sensory feedback in severe sensory loss impairs manipulation capability. We hypothesized that task-oriented training with sensory feedback assistance would improve manipulation capability even without sensory pathway recovery. We developed a system that provides sensory feedback by transcutaneous electrical nerve stimulation (SENS) for patients with sensory loss, and investigated the feasibility of the system in a stroke patient with severe sensory impairment and mild motor deficit. The electrical current was modulated by the force exerted by the fingertips so as to allow the patient to identify the intensity. The patient had severe sensory loss due to a right thalamic hemorrhage suffered 27 months prior to participation in the study. The patient first practiced a cylindrical grasp task with SENS for 1 hour daily over 29 days. Pressure information from the affected thumb was fed back to the unaffected shoulder. The same patient practiced a tip pinch task with SENS for 1 hour daily over 4 days. Pressure information from the affected thumb and index finger was fed back to the unaffected and affected shoulders, respectively. We assessed the feasibility of SENS and examined the improvement of manipulation capability after training with SENS. The fluctuation in fingertip force during the cylindrical grasp task gradually decreased as the training progressed. The patient was able to maintain a stable grip force after training, even without SENS. Pressure exerted by the tip pinch of the affected hand was unstable before intervention with SENS compared with that of the unaffected hand. However, they were similar to each other immediately after SENS was initiated, suggesting that the somatosensory information improved tip pinch performance. The patient's manipulation capability assessed by the Box

  2. Orthodontic Treatment of Maxillary Incisors with Severe Root Resorption Caused by Bilateral Canine Impaction in a Class II Division 1 Patient.

    Science.gov (United States)

    Chang, Na-Young; Park, Jae Hyun; Lee, Mi-Young; Cho, Jin-Woo; Cho, Jin-Hyoung; An, Ki-Yong; Chae, Jong-Moon

    2016-01-01

    This case report shows the successful alignment of bilateral impacted maxillary canines. A 12-year-old male with the chief complaint of the protrusion of his maxillary anterior teeth happened to have bilateral maxillary canine impaction on the labial side of his maxillary incisors. Four maxillary incisors showed severe root resorption because of the impacted canines. The patient was diagnosed as skeletal Class II malocclusion with proclined maxillary incisors. The impacted canine was carefully retracted using sectional buccal arch wires to avoid further root resorption of the maxillary incisors. To distalize the maxillary dentition, two palatal miniscrews were used. After 25 months of treatment, the maxillary canines were well aligned without any additional root resorption of the maxillary incisors.

  3. A Convenient Model of Severe, High Incidence Autoimmune Gastritis Caused by Polyclonal Effector T Cells and without Perturbation of Regulatory T Cells

    Science.gov (United States)

    Tu, Eric; Ang, Desmond K. Y.; Hogan, Thea V.; Read, Simon; Chia, Cheryl P. Z.; Gleeson, Paul A.; van Driel, Ian R.

    2011-01-01

    Autoimmune gastritis results from the breakdown of T cell tolerance to the gastric H+/K+ ATPase. The gastric H+/K+ ATPase is responsible for the acidification of gastric juice and consists of an α subunit (H/Kα) and a β subunit (H/Kβ). Here we show that CD4+ T cells from H/Kα-deficient mice (H/Kα−/−) are highly pathogenic and autoimmune gastritis can be induced in sublethally irradiated wildtype mice by adoptive transfer of unfractionated CD4+ T cells from H/Kα−/− mice. All recipient mice consistently developed the most severe form of autoimmune gastritis 8 weeks after the transfer, featuring hypertrophy of the gastric mucosa, complete depletion of the parietal and zymogenic cells, and presence of autoantibodies to H+/K+ ATPase in the serum. Furthermore, we demonstrated that the disease significantly affected stomach weight and stomach pH of recipient mice. Depletion of parietal cells in this disease model required the presence of both H/Kα and H/Kβ since transfer of H/Kα−/− CD4+ T cells did not result in depletion of parietal cells in H/Kα−/− or H/Kβ−/− recipient mice. The consistency of disease severity, the use of polyclonal T cells and a specific T cell response to the gastric autoantigen make this an ideal disease model for the study of many aspects of organ-specific autoimmunity including prevention and treatment of the disease. PMID:22096532

  4. A Severe Accident Caused by an Ocellate River Stingray (Potamotrygon motoro) in Central Brazil: How Well Do We Really Understand Stingray Venom Chemistry, Envenomation, and Therapeutics?

    Science.gov (United States)

    da Silva, Nelson Jorge; Ferreira, Kalley Ricardo Clementino; Pinto, Raimundo Nonato Leite; Aird, Steven Douglas

    2015-06-18

    Freshwater stingrays cause many serious human injuries, but identification of the offending species is uncommon. The present case involved a large freshwater stingray, Potamotrygon motoro (Chondrichthyes: Potamotrygonidae), in the Araguaia River in Tocantins, Brazil. Appropriate first aid was administered within ~15 min, except that an ice pack was applied. Analgesics provided no pain relief, although hot compresses did. Ciprofloxacin therapy commenced after ~18 h and continued seven days. Then antibiotic was suspended; however, after two more days and additional tests, cephalosporin therapy was initiated, and proved successful. Pain worsened despite increasingly powerful analgesics, until debridement of the wound was performed after one month. The wound finally closed ~70 days after the accident, but the patient continued to have problems wearing shoes even eight months later. Chemistry and pharmacology of Potamotrygon venom and mucus, and clinical management of freshwater stingray envenomations are reviewed in light of the present case. Bacterial infections of stingray puncture wounds may account for more long-term morbidity than stingray venom. Simultaneous prophylactic use of multiple antibiotics is recommended for all but the most superficial stingray wounds. Distinguishing relative contributions of venom, mucus, and bacteria will require careful genomic and transcriptomic investigations of stingray tissues and contaminating bacteria.

  5. Dwarfism in Mice Lacking Collagen-binding Integrins α2β1 and α11β1 Is Caused by Severely Diminished IGF-1 Levels*

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F.; Ehlen, Harald W. A.; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C.; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-01-01

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis. PMID:22210772

  6. Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels.

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F; Ehlen, Harald W A; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-02-24

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis.

  7. A Severe Accident Caused by an Ocellate River Stingray (Potamotrygon motoro in Central Brazil: How Well Do We Really Understand Stingray Venom Chemistry, Envenomation, and Therapeutics?

    Directory of Open Access Journals (Sweden)

    Nelson Jorge da Silva

    2015-06-01

    Full Text Available Freshwater stingrays cause many serious human injuries, but identification of the offending species is uncommon. The present case involved a large freshwater stingray, Potamotrygon motoro (Chondrichthyes: Potamotrygonidae, in the Araguaia River in Tocantins, Brazil. Appropriate first aid was administered within ~15 min, except that an ice pack was applied. Analgesics provided no pain relief, although hot compresses did. Ciprofloxacin therapy commenced after ~18 h and continued seven days. Then antibiotic was suspended; however, after two more days and additional tests, cephalosporin therapy was initiated, and proved successful. Pain worsened despite increasingly powerful analgesics, until debridement of the wound was performed after one month. The wound finally closed ~70 days after the accident, but the patient continued to have problems wearing shoes even eight months later. Chemistry and pharmacology of Potamotrygon venom and mucus, and clinical management of freshwater stingray envenomations are reviewed in light of the present case. Bacterial infections of stingray puncture wounds may account for more long-term morbidity than stingray venom. Simultaneous prophylactic use of multiple antibiotics is recommended for all but the most superficial stingray wounds. Distinguishing relative contributions of venom, mucus, and bacteria will require careful genomic and transcriptomic investigations of stingray tissues and contaminating bacteria.

  8. Severe Pneumonia Caused by Influenza A (H1N1 Virus Successfully Managed with Extracorporeal Life Support in a Comorbid Former Preterm Infant

    Directory of Open Access Journals (Sweden)

    Genny Raffaeli

    2017-03-01

    Full Text Available Influenza A (H1N1 virus infection is a global health burden, leading to significant pediatric morbidity and mortality. Prematurity, young age and comorbidities are important risk factors for unfavorable outcomes. Preventive strategies, such as healthcare workers and household contacts vaccination as well as the implementation of infection control practices during the epidemic season, are crucial to protect the most vulnerable populations. Early diagnosis, timely administration of antiviral drugs and supportive therapy are crucial to lead to a complete recovery. When conventional treatment fails, extracorporeal life support (ECLS may be employed. In neonates and young infants, this high-tech support is burdened by specific technical complexity. Despite the potential risks related to this aggressive approach, ECLS is a life-saving procedure in 65% of pediatric viral pneumonia and in 73% of sepsis cases. Here, we report the successful outcome of a 51-day formerly preterm infant, suffering from a surgical necrotizing enterocolitis (NEC, complicated with hospital-acquired pneumonia due to influenza A (H1N1 virus. She developed a severe respiratory failure, unresponsive to conventional therapy, and successfully treated with ECLS. To our knowledge, this is the first report on the use of ECLS in a formerly preterm infant, suffering from NEC complicated by influenza A (H1N1 virus infection.

  9. Report of Chinese family with severe dermatitis, multiple allergies and metabolic wasting syndrome caused by novel homozygous desmoglein-1 gene mutation.

    Science.gov (United States)

    Cheng, Ruhong; Yan, Ming; Ni, Cheng; Zhang, Jia; Li, Ming; Yao, Zhirong

    2016-10-01

    Recently, homozygous mutations in the desmoglein-1 (DSG1) gene and heterozygous mutation in the desmoplakin (DSP) gene have been demonstrated to be associated with severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome (Mendelian Inheritance in Man no. 615508). We aim to identify the molecular basis for a Chinese pedigree of SAM syndrome. A Chinese pedigree of SAM syndrome was subjected to mutation detection in the DSG1 gene. Sequence analysis of the DSG1 gene and quantitative reverse transcriptase polymerase chain reaction analysis for gene expression of DSG1 using cDNA derived from the epidermis of patients and controls were both performed. Skin biopsies were also taken from patients for pathological study and transmission electron microscopy observation. Novel homozygous splicing mutation c.1892-1delG in the exon-intron border of the DSG1 gene has been demonstrated to be associated with SAM syndrome. We report a new family of SAM syndrome of Asian decent and expand the spectrum of mutations in the DSG1 gene. © 2016 Japanese Dermatological Association.

  10. A dominant mutation of TWISTED DWARF 1 encoding an alpha-tubulin protein causes severe dwarfism and right helical growth in rice.

    Science.gov (United States)

    Sunohara, Hidehiko; Kawai, Takayuki; Shimizu-Sato, Sae; Sato, Yutaka; Sato, Kanna; Kitano, Hidemi

    2009-06-01

    Dwarfism is a common type of mutation in many plant species. The pathways and factors regulating biosynthesis and signaling of several plant growth regulators have been clarified through analyses of dwarf mutants in rice, Arabidopsis, pea, and maize. However, the genetic mechanisms controlling dwarfism are not well characterized, and the causal genes underlying most dwarf mutants are still uncovered. Here, we report a dominant mutant, Twisted dwarf 1-1 (Tid1-1), showing dwarfism and twisted growth in rice. Tid1-1 exhibit right helical growth of the leaves and stem and shortening of the roots. They also show an increased number of cells in the shoot apical meristem. Cells in the leaves of Tid1-1 are often ill-shapen, possibly owing to irregular cell division. Cell elongation in roots is suppressed in the elongation zone, and cells in the root apical meristem are enlarged. Map-based cloning of TID1 revealed that it encodes an alpha-tubulin protein comprising microtubules and is an ortholog of Arabidopsis LEFTY genes. Our analysis of the Tid1-1 mutant revealed that the dynamics of microtubules affects not only anisotropic growth in both dicots and monocots, but also meristematic activity and gross plant morphology.

  11. Severe IgE-mediated anaphylaxis following consumption of fried frog legs: definition of alpha-parvalbumin as the allergen in cause.

    Science.gov (United States)

    Hilger, C; Grigioni, F; Thill, L; Mertens, L; Hentges, F

    2002-11-01

    IgE-mediated allergic reactions to bullfrog and edible frog have been reported. The implicated allergens have not been defined so far. The frog material and the patient's serum from a case of severe food-induced anaphylaxis were used to define the implicated allergen at the protein and DNA level. Immunoblotting techniques and N-terminal protein microsequencing were used to define the allergen recognized by the patient's serum. Back translation from the identified protein sequence was used to design degenerated primers to amplify the allergen's cDNA by polymerase chain reaction (PCR). We defined the nucleotide sequence of the allergen from the frog of Indonesian origin that was consumed by the patient, and the homologous cDNA from Rana esculenta. Protein microsequencing revealed that the implicated frog allergen belonged to the parvalbumin family. cDNAs coding for alpha- and beta-parvalbumin of R. esculenta and Rana species were cloned. Recombinant proteins were expressed in Escherichia coli. The patient's serum IgE antibodies recognized parvalbumin prepared from frog muscle and recombinant alpha-parvalbumin from R. species but not from R. esculenta. Recombinant beta-parvalbumin was not recognized by the IgE antibodies. This work defines at the protein and DNA levels alpha-parvalbumin as the allergen implicated in a case of IgE-mediated anaphylaxis to frog muscle. It also shows that a protein belonging to the parvalbumin family is implicated in type I allergies outside the fish species.

  12. Aparición de episodios de neutropenia febril tras la quimioterapia citostática en el paciente oncológico Appearance of febrile neutropenia episodes after cytostatic therapy on Oncology patients

    Directory of Open Access Journals (Sweden)

    Leonardo Lami Casaus

    2009-12-01

    Full Text Available El tratamiento con drogas citotóxicas en el paciente oncológico, tiene como toxicidad limitante de dosis más común la neutropenia y sus complicaciones infecciosas. Su aparición provoca retrasos y reducción de dosis en los ciclos posteriores de quimioterapia, así como deterioro en la calidad de vida de los pacientes. El colectivo de Medicina Oncológica, que incluye el Servicio de Farmacia, decidió realizar un estudio, con el objetivo de analizar la aparición de neutropenia febril tras la administración de la terapia citotóxica y la presencia de otros factores que pueden incrementar el riesgo de estas reacciones. Se estudiaron los 42 pacientes que ingresaron con neutropenia febril tras el tratamiento citotóxico en el periodo comprendido entre febrero y agosto del 2007. Se recogieron variables biomédicas del grupo de pacientes incluidos y se analizó el tratamiento citostático empleado previamente. El grupo de edad que prevaleció fue el de los pacientes mayores de 50 años, con un predomino del sexo masculino y los estadios avanzados con afecciones asociadas. Las localizaciones tumorales más frecuentes radicaron en mama, pulmón y linfoma no Hodgkin. El citostático más señalado en casos de neutropenia febril resultó la adriamicina con un 71,4 %, seguido de la ciclofosfamida con 52,4 %. Los factores que más se asociaron con la aparición de neutropenia febril fueron: quimioterapia con antraciclinas, la edad mayor de 50 años, estadios avanzados y presencia de enfermedades asociadas.Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and

  13. Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors.

    Science.gov (United States)

    Mastrodemou, Semeli; Stalika, Evangelia; Vardi, Anna; Gemenetzi, Katerina; Spanoudakis, Michalis; Karypidou, Maria; Mavroudi, Irene; Hadzidimitriou, Anastasia; Stavropoulos-Giokas, Catherine; Papadaki, Helen A; Stamatopoulos, Kostas

    2017-12-01

    Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8 + cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.

  14. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Changji City of Xinjiang Uygur Autonomous Region: the China Nine-Province survey].

    Science.gov (United States)

    Ma, Xian-zhi; Zhao, Jia-liang; Ellwein, Leon B; Wei, Bin; Chen, Jing; Ye, Ying; Tang, Xiao-dong; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Changji City of Xinjiang Uygur Autonomous Region, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5714 individuals aged ≥ 50 years in Changji City. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to received visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands seven hundreds and fourteen individuals were enumerated and 5250 persons were examined, the response rate was 91.88%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 0.74% (39/5250) and 3.83% (201/5250) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.33% (70/5250) and 8.02% (421/5250) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 617.06, P = 0.000) , illiterate (trend χ(2) = 222.35, P = 0.000) persons. Cataract and was the first leading cause of blindness and visual impairment, the retinal diseases, including age-related macular degeneration, high myopic retinopathy, and diabetic retinopathy, were the

  15. Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy.

    Science.gov (United States)

    Laoprasopwattana, Kamolwish; Khwanna, Thida; Suwankeeree, Pussayaban; Sujjanunt, Tipwan; Tunyapanit, Wanutsanun; Chelae, Sureerat

    2013-03-01

    Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, -23.0%; 95% confidence interval: -45.0% to -0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

  16. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Longyao County of Hebei Province:the China Nine-Province survey].

    Science.gov (United States)

    Lü, Jian-hua; Zhao, Jia-liang; Ellwein, Leon B; Li, Shan-yu; Han, Dong; Yan, Zhong-yang; Zhang, Hong-bin; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Longyao County, Hebei Province, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5527 individuals aged ≥ 50 years in Longyao County. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands five hundreds and twenty-seven individuals were enumerated and 5051 persons were examined, the response rate was 91.39%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 1.05% (53/5051) and 3.46% (175/5051) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.48% (75/5051) and 7.94% (401/5051) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 897.27, P = 0.000) , female (χ(2) = 30.32, P = 0.000), illiterate (trend χ(2) = 83.20, P = 0.000) persons. Cataract was still the first leading cause of blindness. Un-corrected refractive error also was the main cause of visual impairment. The prevalence of blindness and moderate and severe

  17. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yongchuan District of Chongqing City: the China Nine-Province survey].

    Science.gov (United States)

    Yin, Zheng-qin; Zhao, Jia-liang; Li, Ping-hua; Ellwein, Leon b; Song, Sheng-fang; Li, Fu-liang; Wang, Ting-gang; Ren, Yi-ming; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yongchuan of Chongqing City, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5663 individuals aged ≥ 50 years in Yongchuan District. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands six hundreds and sixty-three individuals were enumerated and 5390 persons were examined, the response rate was 95.18%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 2.12% (114/5390) and 5.40% (291/5390) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 2.49% (134/5390) and 10.71% (577/5390) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 951.32, P = 0.000) , female (χ(2) = 33.35, P = 0.000) and illiterate (trend χ(2) equals; 141.32, P = 0.000) persons. Cataract was still the first leading cause of blindness and visual impairment.Un-corrected refractive error also was the main cause of visual impairment. The prevalence

  18. Validasi Sistem Skoring Rondinelli untuk Mendeteksi Komplikasi Infeksi Berat pada Pasien Leukemia Limfoblastik Akut L1 dengan Demam Neutropenia Selama Kemoterapi Fase Induksi

    Directory of Open Access Journals (Sweden)

    Renno Hidayat

    2016-11-01

    Kesimpulan. Sistem skoring Rondinelli merupakan instrumen yang cukup baik untuk mendeteksi komplikasi infeksi berat pada anak dengan LLA-L1 yang mengalami demam neutropenia selama pemberian kemoterapi fase induksi.

  19. Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

    Science.gov (United States)

    Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

    2016-05-26

    Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

  20. Neutropenia febril em pacientes com câncer de mama submetidas à quimioterapia: experiência de 12 anos Febrile neutropenia in patients with breast cancer submitted to chemotherapy: a 12 year experience

    Directory of Open Access Journals (Sweden)

    Omero Benedicto Poli Neto

    2004-12-01

    Full Text Available OBJETIVOS: Identificar as características das pacientes com câncer de mama que desenvolveram neutropenia febril, estabelecer fatores de risco para a sua ocorrência e indicadores de evolução desfavorável. MÉTODOS: Realizamos um estudo caso-controle com 65 pacientes. Foram incluídas 13 pacientes que desenvolveram neutropenia febril e quatro controles por caso pareados por data e número de ciclos de quimioterapia prévios, drogas e doses empregadas. Os dados clínicos e laboratoriais foram obtidos dos prontuários médicos. Utilizamos odds ratio (OR e intervalo de confiança (IC de 95% para estimar a significância dos fatores de risco. RESULTADOS: Identificamos dois fatores de risco associados à ocorrência de neutropenia febril: a realização de quimioterapia nas primeiras 24 horas após a cirurgia (OR: 159,9 IC 95%: 9,5 a 2699 e a realização concomitante de quimioterapia e radioterapia da mama (OR: 108,3 IC 95%: 4,9 a 2391. Não observamos diferenças significativas entre casos e controles quanto à idade, índice de massa corporal e contagem de neutrófilos e monócitos antes da quimioterapia. Três pacientes foram a óbito (23,1%. Duas delas tinham idade superior a 60 anos, não apresentavam comorbidades, tinham recebido o primeiro ciclo de CMF nas primeiras 24 horas após a cirurgia e tiveram infecção de sítio cirúrgico. CONCLUSÕES: Os principais fatores de risco associados a neutropenia febril em pacientes com câncer de mama foram quimioterapia nas primeiras 24 horas após a cirurgia, e uso concomitante de quimioterapia e radioterapia da mama. Nosso estudo mostra, portanto, que estas situações devem ser evitadas.PURPOSE: To identify the characteristis of patients with breast cancer who developed febrile neutropenia and to establish risk factors for its incidence and parameters for an unfavorable evolution. PATIENTS AND METHODS: A case-control study was performed and included 65 patients: 13 patients presented febrile

  1. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Luxi County of Yunnan Province: the China Nine-Province survey].

    Science.gov (United States)

    Cai, Ning; Yuan, Yuan-sheng; Zhao, Jia-liang; Zhong, Hua; Ellwein, Leon B; Chen, Miao-miao; Dan, Ai-hua; Sun, Peng; Luo, Ting-hao; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Luxi County of Yunnan Province, China. It was a population-based cross-section study. Geographically defined cluster sampling was used in randomly selecting 5575 individuals aged ≥ 50 years in Luxi County. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands five hundreds and seventy-five individuals were enumerated and 5151 persons were examined, the response rate was 92.39%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 4.95% (255/5151) and 9.51% (490/5151) , respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 5.40% (278/5151) and 15.84% (816/5151) , respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (χ(2) = 1349.21, P = 0.000) , illiterate (χ(2) = 203.55, P = 0.000) persons. Cataract was still the first leading cause of blindness and visual impairment. The prevalence of blindness and moderate and severe visual impairment is highest in China Nine-Province Survey among older adults aged ≥ 50 years

  2. Magnitude and Causes of Low Vision Disability (Moderate and Severe Visual Impairment) among Students of Al-Noor Institute for the Blind in Al-Hassa, Saudi Arabia: A case series.

    Science.gov (United States)

    Al-Wadani, Fahad; Khandekar, Rajiv; Al-Hussain, Muneera A; Alkhawaja, Ahmed A; Khan, Mohammed Sarfaraz; Alsulaiman, Ramzy A

    2012-02-01

    This study aimed to estimate the magnitude and causes of low vision disability (severe visual impairment [SVI] and moderate visual impairment [MVI]) among students at Al-Noor Institute for the Blind (NIB) in Al-Hassa, Saudi Arabia in 2006. An optometrist conducted refraction of 122 eyes of the 61 students (27 boys and 34 girls) with MVI (vision visual acuity was ≥6/18 and in 28 (23%) eyes, it was visual impairment in 16 (13.1%) and 9 (7.4%) eyes. These students were prescribed optical and non-optical low vision aids. Retinal disease was the main cause of SVI and MVI in our series. Some students at Al-Noor Institute for the Blind have curable low vision conditions. Rehabilitation of low vision disability should be different from that offered to the absolutely blind.

  3. CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

    Directory of Open Access Journals (Sweden)

    M. V. Peshikova

    2005-01-01

    Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

  4. [Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

    Science.gov (United States)

    Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

    2015-09-01

    The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).

  5. 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.

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

    International Nuclear Information System (INIS)

    Ali, Syed Zama; Clarke, Michael John; Kannivelu, Anbalagan; Chinchure, Dinesh; Srinivasan, Sivasubramanian

    2014-01-01

    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 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 99m technetium sulfur colloid SPECT/CT imaging in this rare condition.

  7. Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

    Science.gov (United States)

    Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

    2016-07-01

    Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  8. Sunitinib-induced hypertension, neutropenia and thrombocytopenia as predictors of good prognosis in metastatic renal cell carcinoma patients

    DEFF Research Database (Denmark)

    Rautiola, Juhana; Donskov, Frede; Peltola, Katriina

    2016-01-01

    OBJECTIVES: To evaluate the clinical significance of hypertension, neutropenia and thrombocytopenia as possible new biomarkers of sunitinib efficacy in non-trial metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: 181 consecutive mRCC patients were treated with sunitinib. Thir...... of sunitinib efficacy patients with mRCC. Our results may help to individualize sunitinib dosing during therapy based on these common sunitinib-related AEs....

  9. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial.

    Science.gov (United States)

    Blackwell, Kimberly; Donskih, Roman; Jones, C Michael; Nixon, Allen; Vidal, Maria J; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-07-01

    Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count prevention of neutropenia in patients with early-stage breast cancer receiving TAC. The granulocyte colony-stimulating factor pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. Biosimilars are biologics with similar quality, safety, and efficacy to a reference product that may increase the affordability of treatment compared with their reference compounds. There are currently no approved biosimilars of pegfilgrastim in highly regulated markets. No previous phase III studies have been performed with LA-EP2006. PROTECT-2 was conducted to confirm the similarity of the proposed biosimilar LA-EP2006 to pegfilgrastim. Biosimilar pegfilgrastim (LA-EP2006) may benefit oncology patients by offering increased access to biological treatments that may improve clinical outcomes. This means that patients could potentially be treated prophylactically with biologics rather than only after complications have occurred. ©AlphaMed Press.

  10. A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned From the ANC Study Group.

    Science.gov (United States)

    Lyman, Gary H; Poniewierski, Marek S

    2017-12-01

    Neutropenia and its complications, including febrile neutropenia (FN), represent major toxicities associated with cancer chemotherapy, resulting in considerable morbidity, mortality, and costs. The myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) have been shown to reduce the risk of neutropenia complications while enabling safe and effective chemotherapy dose intensity. Concerns about the high costs of these agents along with limited physician adherence to clinical practice guidelines, resulting in both overuse and underuse, has stimulated interest in models for individual patient risk assessment to guide appropriate use of G-CSF. In a model developed and validated by the ANC Study Group, half of patients were classified as high risk and half as low risk based on patient-, disease-, and treatment-related factors. This model has been further validated in an independent patient population. Physician-assessed risk of FN, as well as the decision to use prophylactic CSF, has been shown to correlate poorly with the FN risk estimated by the model. Additional modeling efforts in both adults and children receiving cancer treatment have been reported. Identification of patients at a high individual risk for FN and its consequences may offer the potential for optimal chemotherapy delivery and patient outcomes. Likewise, identification of patients at low risk for neutropenic events may reduce costs when such supportive care is not warranted. This article reviews and summarizes FN modeling studies and the opportunities for personalizing supportive care in patients receiving chemotherapy. Copyright © 2017 by the National Comprehensive Cancer Network.

  11. Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in vitro sensitivity data and clinical response to empirical antibiotic therapy

    International Nuclear Information System (INIS)

    Ansari, S.H.; Nasim, S.; Ahmed, A.; Irfan, M.; Ishaque, A.; Farzana, T.; Panjwani, V.K.; Taj, M.; Shamsi, T.S.

    2006-01-01

    To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. (author)

  12. Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

    Science.gov (United States)

    Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

    2016-03-01

    This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of