Rubella associated with hemophagocytic syndrome. First report in a male and review of the literature

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Makram Koubaa

2012-08-01

Full Text Available A 22-year-old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C, generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positif and the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have rubella-associated hemophagocytic syndrome. We report herein the first case in a man and the sixth case of rubella-associated hemophagocytic syndrome in the literature by search in Pub Med till March 2012.

Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis.

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Su, I J; Hsu, Y H; Lin, M T; Cheng, A L; Wang, C H; Weiss, L M

1993-09-15

The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS.

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Wenli Yang

Full Text Available The hepatopulmonary syndrome (HPS develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2 play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL. We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064 induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.

A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

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Sekiguchi, Yasunobu; Shimada, Asami; Imai, Hidenori; Wakabayashi, Mutsumi; Sugimoto, Keiji; Nakamura, Noriko; Sawada, Tomohiro; Komatsu, Norio; Noguchi, Masaaki

2014-01-01

The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

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Larroche, C; Scieux, C; Honderlick, P; Piette, A M; Morinet, F; Blétry, O

2002-10-01

Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

Fulminant hemophagocytic lymphohistiocytosis induced by pandemic A (H1N1 influenza: a case report

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Wacrenier Agnès

2011-07-01

Full Text Available Abstract Introduction Hemophagocytic lymphohistiocytosis induced by viral diseases is a well recognized entity. Severe forms of H5N1 influenza are known to be associated with symptoms very similar to a reactive hemophagocytic syndrome. We report a case of fulminant lymphohistiocytosis associated with the pandemic A (H1N1 variant. Case presentation A 42-year-old Caucasian woman developed a syndrome of fatal hemophagocytic lymphohistiocytosis shortly after H1N1 influenza. Initial symptoms of the viral disease were unusual, with acute abdominal involvement. Our patient's course was complicated by diffuse skin rash and ileal ischemia. Our patient died of refractory shock and multi-organ failure. Skin, ileum and colon histology was consistent with an acute apoptosis combined with an increased cellular regeneration. Conclusions Influenza may be complicated by severe forms of hemophagocytic lymphohistiocytosis. To ensure early recognition and treatment, physicians should be aware of the possible induction of the syndrome by the novel H1N1 variant. The rapid occurrence of a multi-organ involvement with evocative biological features of macrophage activation should alert clinicians.

Generation of Hermansky Pudlak syndrome type 2 (HPS2 induced pluripotent stem cells (iPSCs

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Jean Ann Maguire

2016-03-01

Full Text Available Hermansky–Pudlak syndrome type 2 (HPS2 is a rare autosomal recessive disorder resulting from functional mutations in the adaptor-related protein complex 3, beta 1 subunit (AP3B1 gene. This gene plays a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Here we describe the generation of an HPS2 iPS cell line (CHOPHPS2 using a Cre-excisable polycistronic STEMCCA lentivirus. This line was derived from human fibroblasts isolated from a patient carrying two mutations in the AP3B1 gene. The patient presented with severe neutropenia, ocular albinism, interstitial pulmonary fibrosis, hemorrhagic diathesis, and an absence of platelet-dense granules.

Hemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis in the setting of Acquired Immunodeficiency Syndrome (AIDS).

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Asanad, Samuel; Cerk, Brendan; Ramirez, Veronica

2018-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease involving immune system over-activation leading to hemophagocytosis. HLH requires early diagnosis and prompt treatment initiation, especially in patients with Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged male with AIDS and renal failure, who developed HLH secondary to disseminated histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines was deferred and treatment focused instead on anti-fungal therapy. Anti-retroviral therapy followed thereafter.

Hemophagocytic lymphohistiocytosis: a case series of a Brazilian institution

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Daniela Guimarães Rocha Ferreira

2014-12-01

Full Text Available Objective:To describe the clinical and laboratory presentation of hemophagocytic lymphohistiocytosis in children treated at a referral institution.Methods:A retrospective descriptive study was carried out of seven children diagnosed with hemophagocytic lymphohistiocytosis between 2010 and 2012. The criteria for diagnosis were those proposed by the Histiocyte Society. When indicated, immunochemotherapy was prescribed according to the HLH94 and HLH2004 protocols of the Histiocyte Society.Results:The patients' ages at diagnosis ranged from one month to nine years. All patients had splenomegaly, fever, anemia, thrombocytopenia, hyperferritinemia and hypertriglyceridemia. Bone marrow hemophagocytosis was detected in six patients. In six cases, infectious diseases triggered the syndrome. In two cases, associated with visceral leishmaniasis, remission was achieved after treatment of the underlying infection. Three patients, who had Epstein–Barr-related hemophagocytic lymphohistiocytosis, required treatment with immunochemotherapy. They are alive and in remission; one patient had symptoms of juvenile rheumatoid arthritis and another, who was suspected of having primary hemophagocytic lymphohistiocytosis, entered into remission after bone marrow transplantation. Two deaths (28.6% occurred in patients with suspected primary hemophagocytic lymphohistiocytosis; one whose clinical picture was triggered by cytomegalovirus infection did not respond to immunochemotherapy and the other died before any specific treatment was provided.Conclusion:As reported before, hemophagocytic lymphohistiocytosis has a multifaceted presentation with nonspecific signs and symptoms. In secondary forms, remission may be achieved by treating the underlying disease. In the primary forms, remission may be achieved with immunochemotherapy, but bone marrow transplantation is required for cure.

Neuromyelitis optica, atypical hemophagocytic lymphohistiocytosis and heterozygous perforin A91V mutation.

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Palterer, Boaz; Brugnolo, Francesca; Sieni, Elena; Barilaro, Alessandro; Parronchi, Paola

2017-10-15

Neuromyelitis optica is an autoimmune demyelinating inflammatory disease characterized by optic neuritis and myelitis with anti-aquaporin 4 antibodies. Hemophagocytic lymphohistiocytosis is a severe systemic inflammatory syndrome that can present in a genetic primary form or secondarily to infective, neoplastic or autoimmune diseases. Our case discusses the first reported case of atypical late-onset hemophagocytic lymphohistiocytosis in a patient with neuromyelitis optica, with multiple triggering factors and carrying the common A91V hypomorphic perforin mutation, that blurs the distinction between primary and secondary forms. Copyright © 2017 Elsevier B.V. All rights reserved.

DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS.

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Rebecca Brocato

Full Text Available Andes virus (ANDV is the predominant cause of hantavirus pulmonary syndrome (HPS in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35-40%. Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos. The natural "despeciation" of the duck IgY (i.e., Fc removed results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥ 5,000 neutralizing antibody units (NAU/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT. Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: response to HLH-04 treatment protocol.

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Jiménez-Hernández, Elva; Martínez-Villegas, Octavio; Sánchez-Jara, Berenice; Martínez-Martell, María Angélica; Hernández-Sánchez, Beatriz; Loza-Santiaguillo, Paloma Del Rocío; Pedro-Matías, Eduardo; Arellano-Galindo, José

Hemophagocytic syndrome, macrophage activation syndrome, reactive histiocytosis or hemophagocytic lymphohistiocytosis (HLH) represent a group of diseases whose common thread is reactive or neoplastic mononuclear phagocytic system cells and dendritic cell proliferation. We present a case of an HLH probably associated with Epstein-Barr virus (EBV) in a 4-year-old male patient treated with HLH-04 protocol. Viral etiology in HLH is well accepted. In this case, clinical picture of HLH was assumed secondary to EBV infection because IgM serology at the time of clinical presentation was the only positive factor in the viral panel. Diagnosis of HLH is the critical first step to successful treatment. The earlier it is identified, the less the tissue damage and reduced risk of multiple organ failure, which favors treatment response. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

A web-based delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients.

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Hejblum, Gilles; Lambotte, Olivier; Galicier, Lionel; Coppo, Paul; Marzac, Christophe; Aumont, Cédric; Fardet, Laurence

2014-01-01

The diagnosis of the reactive form of hemophagocytic syndrome in adults remains particularly difficult since none of the clinical or laboratory manifestations are specific. We undertook a study in order to elicit which features constitute helpful criteria for a positive diagnosis. In this Delphi study, the features investigated in the questionnaire and the experts invited to participate in the survey were issued from a bibliographic search. The questionnaire was iteratively proposed to experts via a web-based application with a feedback of the results observed at the preceding Delphi round. Experts were asked to label each investigated criterion in one of the following categories: absolutely required, important, of minor interest, or not assessable in the routine practice environment. A positive consensus was a priori defined as at least 75% answers observed in the categories absolutely required and important. The questionnaire investigated 26 criteria and 24 experts originating from 13 countries participated in the second and final Delphi round. A positive consensus was reached for the nine following criteria: unilineage cytopenia, bicytopenia, pancytopenia, presence of hemophagocytosis pictures on a bone marrow aspirate or on a tissue biopsy, high ferritin level, fever, organomegaly, presence of a predisposing underlying disease, and high level of lactate dehydrogenase. A negative consensus was reached for 13 criteria, and an absence of consensus was observed for 4 criteria. The study constitutes the first initiative to date for defining international guidelines devoted to the positive diagnosis of the reactive form of hemophagocytic syndrome.

A deletion in the Hermansky-Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish.

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Li, Yueru; Geng, Xin; Bao, Lisui; Elaswad, Ahmed; Huggins, Kevin W; Dunham, Rex; Liu, Zhanjiang

2017-06-01

Albinism is caused by a series of genetic abnormalities leading to reduction of melanin production. Albinism is quite frequent in catfish, but the causative gene and the molecular basis were unknown. In this study, we conducted a genome-wide association study (GWAS) using the 250 K SNP array. The GWAS analysis allowed mapping of the albino phenotype in the Hermansky-Pudlak syndrome 4 (Hps4) gene, which is known to be involved in melanosome biosynthesis. Sequencing analysis revealed that a 99-bp deletion was present in all analyzed albino catfish at the intron 2 and exon 3 junction. This deletion led to the skipping of the entire exon 3 which was confirmed by RT-PCR. Therefore, Hps4 was determined to be the candidate gene of the catfish albinism.

Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

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Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke

2010-01-01

Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weaknes...

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

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Irina Gavrilovskaya

2012-01-01

Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Mycobacterium iranicum bacteremia and hemophagocytic lymphohistiocytosis: a case report.

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Grandjean Lapierre, Simon; Toro, Alexandre; Drancourt, Michel

2017-08-08

Mycobacterium iranicum has recently been recognised as an opportunistic human pathogen. Although infectious conditions represent frequent triggers for hemophagocytic lymphohistiocytosis, non-tuberculous mycobacterial infections are rarely associated with this entity. To this date, M. iranicum infection has never been reported in France, has never been associated with hemophagocytic lymphohistiocytosis and has never been found to be multi-resistant on standardized antimicrobial susceptibility testing. We report a case of a French Caucasian man with secondary hemophagocytic lymphohistiocytosis in the context of M. iranicum bacteraemia and Hodgkin's disease. We review available data concerning M. iranicum antimycobacterial susceptibility testing and treatment outcomes. We also review the association between hemophagocytic lymphohistiocytosis and non-tuberculous mycobacterial infections. Interpretation of M. iranicum positive cultures remains a clinical challenge and non-tuberculous mycobacterial infections need to be considered in secondary hemophagocytic lymphohistiocytosis differential diagnosis.

Hamartomatous polyposis syndromes

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Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

2014-01-01

Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

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Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype

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James C. Hart

2017-09-01

Full Text Available Here, we present and characterize the spontaneous X-linked recessive mutation casper, which causes oculocutaneous albinism in threespine sticklebacks (Gasterosteus aculeatus. In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO, the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19 near the stickleback ortholog of Hermansky-Pudlak syndrome 5 (Hps5. casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5, predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish.

Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome

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Young Min Hong

2012-06-01

Full Text Available Hemorrhagic fever with renal syndrome (HFRS is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS. HPS progression to a life-threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS.

Infection Associated Secondary Hemophagocytic Lymphohistiocytosis in Sepsis Syndromes - A Tip of an Iceberg.

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Agarwal, Arun; Agarwal, Aakanksha

2017-10-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare, underdiagnosed, fatal and devastating hyperinflammatory syndrome that has gained increasing recognition over the past decade. Patients with HLH present with clinical and laboratory evidence of uncontrolled inflammation. Delay in diagnosis and management inevitably leads to a rapidly progressive and fatal course. In this case series, we present 7 cases of secondary HLH (sHLH) in adults with their presentation, course, and outcomes. We retrospectively looked at the 7 cases of secondary HLH who were diagnosed and managed in our institute between January 2013 and august 2015. Medical records were retrieved from medical records department and data analyzed and tabulated. The median age at diagnosis was 35 years (age range 26-72 years). Diagnosis was based on HLH 2004 diagnostic criteria. We report profile of 7 adult patients with sHLH. All patients had a short history of illness (<2 weeks) and presented uniformly with prolonged fever, bi or trilineage cytopenia and multiorgan dysfunction syndrome (MODS) at admission or developed MODS during the course of their illness. None of them had prediagnosed HLH. All patients fulfilled 5 to 6 of 8 criteria as per HLH 2014 diagnostic criteria. The median length of hospital stay was 12 days (range 7-50 days) and the median time to diagnosis was 5 days (range 3 to 21 days). Mortality was 57%. HLH is a rare and under-diagnosed clinical syndrome and is rapidly fatal if not diagnosed and managed timely. The cases reported in literature probably represent a tip of an iceberg of large number of undiagnosed cases mostly labeled as sepsis with MODS in critical care units. sHLH should be suspected in any patient who present with persistent and prolonged fever, transaminitis, cytopenia, and high serum Ferritin or dramatically rising serial serum Ferritin. Early diagnosis and prompt aggressive treatment are vital for patients' survival and favorable outcome.

Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital

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Baijayantimala Mishra

2012-01-01

Full Text Available Background : Hemophagocytic syndrome (HPS is a rare clinicopathological condition characterized by the activation of macrophages with prominent hemophagocytosis in bone marrow and other reticulo-endothelial systems. HPS can be familial or secondary to infections including viruses. Aim : To study the viral markers in patients with HPS. Materials and Methods : Serum samples of patients with HPS and control group were screened for anti EBV VCA IgM, and IgG, anti-Parvo B19 IgM, and anti-CMV IgM antibodies using commercially available ELISA kits and CMV and ParvoB19 DNA by polymerase chain reaction (PCR. Results and Discussion : The present prospective study reports the profile of viral markers in HPS cases from north India. Among the 14 HPS cases 43% (6/14 were positive for at least one viral marker tested, of which EBV was found to be the most prevalent (3/6: 50% followed by parvovirus B19(2/6: 33% and cytomegalovirus (1/6: 17%. Mortality was noted in 33% of virus associated HPS patients. Our study highlights the higher association of Epstein-Barr virus (EBV with HPS as compared to other viruses along with higher rate of mortality in both parvovirus B 19 and EBV associated HPS.

Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

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Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke

2010-01-01

Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

Could HPS Improve Problem-Solving?

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Coelho, Ricardo Lopes

2013-05-01

It is generally accepted nowadays that History and Philosophy of Science (HPS) is useful in understanding scientific concepts, theories and even some experiments. Problem-solving strategies are a significant topic, since students' careers depend on their skill to solve problems. These are the reasons for addressing the question of whether problem solving could be improved by means of HPS. Three typical problems in introductory courses of mechanics—the inclined plane, the simple pendulum and the Atwood machine—are taken as the object of the present study. The solving strategies of these problems in the eighteenth and nineteenth century constitute the historical component of the study. Its philosophical component stems from the foundations of mechanics research literature. The use of HPS leads us to see those problems in a different way. These different ways can be tested, for which experiments are proposed. The traditional solving strategies for the incline and pendulum problems are adequate for some situations but not in general. The recourse to apparent weights in the Atwood machine problem leads us to a new insight and a solving strategy for composed Atwood machines. Educational implications also concern the development of logical thinking by means of the variety of lines of thought provided by HPS.

HPS simulation and acceptance

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Mundim, Luiz Martins [UERJ, Rio de Janeiro, RJ (Brazil); Pol, Maria Elena [CBPF, Rio de Janeiro, RJ (Brazil)

2013-07-01

Full text: The High Precision Spectrometer (HPS) is a proposal of sub-detector to be installed in the region of 200-240m from each side of CMS along the LHC beam-line to measure scattered protons from exclusive centrally produced processes, pp → p + X + p. In order to study the protons that reach the detectors, the beam-line of the LHC accelerator has to be taken into account, as the particles are deflected by dipoles and suffer the influence of quadrupoles and other beam devices. The LHC team provides a detailed description of these elements, currents, energies, magnetic fields, and all the information needed to study the propagation of the protons. The program HECTOR, developed at the University of Louvain, uses the information from LHC to calculate at any point along the beam-line the kinematic quantities that characterize the scattered protons. A simple minded program was initially developed for the preliminary studies of acceptances varying the position and size of the foreseen detectors. Also, it took into account vertex and position smearing, to simulate a realistic resolution of the tracking detectors. These studies were performed using a particle gun generator which shoot protons from the IP within reasonable ranges of possible t and ξ (the square of the four-momentum transfer and the fractional energy loss of the outgoing proton in a diffractive collision), and propagated them to the position of the tracking detectors. These kinematic quantities were reconstructed back at the IP using the transport equations from HECTOR. This simplified simulation was afterwards interfaced with the full software of CMS, CMSSW, in such a way that when a diffractive event was fully simulated and reconstructed in the central detector, the outgoing protons were treated by the HPS software and then the complete (CMS+HPS) event was output. The ExHuME generator was used to produce Monte Carlo simulations to study the mass acceptance of the HPS detector, and central and

Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

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Samantha K Dunmire

Full Text Available Epstein-Barr Virus (EBV causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza, respiratory syncytial virus (RSV, human rhinovirus (HRV, attenuated yellow fever virus (YFV, and Dengue fever virus (DENV, revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

Primary EBV Infection Induces an Expression Profile Distinct from Other Viruses but Similar to Hemophagocytic Syndromes

Science.gov (United States)

Dunmire, Samantha K.; Odumade, Oludare A.; Porter, Jean L.; Reyes-Genere, Juan; Schmeling, David O.; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C.; Balfour, Henry H.; Hogquist, Kristin A.

2014-01-01

Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans. PMID:24465555

The HPS experiment at JLab

Directory of Open Access Journals (Sweden)

De Napoli Marzio

2017-01-01

Full Text Available Many Beyond-Standard-Model theories predict a new massive gauge boson, such as a “dark” or “heavy photon”. The heavy photon is expected to mix with the Standard Model photon through kinetic mixing and therefore have a small coupling to electric charge. The Heavy Photon Search (HPS experiment is searching for a heavy photon at the Thomas Jefferson National Accelerator Facility (JLab, in the mass range 20-500 MeV/c2. In particular HPS looks for the e+e− decay channel of heavy photons radiated by electron Bremsstrahlung, employing both an invariant mass search and detached vertexing techniques. The experiment employs a compact forward spectrometer comprising silicon microstrip detectors for vertexing and tracking and an electromagnetic calorimeter for particle identification and triggering. HPS took data successfully in 2015 and 2016 at 1.05 GeV and 2.3 GeV beam energies, respectively. First results are expected to be presented soon.

Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A

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Ren'an Chen

2010-11-01

Full Text Available A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.

Det hepatopulmonale syndrome

DEFF Research Database (Denmark)

Eibye, Simone Bendix; Christensen, Erik

2016-01-01

The hepatopulmonary syndrome (HPS) - a complication of liver disease - seems to be underdiagnosed, probably because of decreased awareness. HPS consists of the triade liver disease, intrapulmonary vascular dilatation and as a consequence arterial hypoxaemia. No medical therapy has proven effectiv...... perhaps with the exception of garlic, which has been effective in one controlled clinical trial. However, liver transplantation seems to improve HPS in most cases. Liver patients with unexplained hypoxaemia should be investigated for HPS....

Identification of a novel mutation in HPS6 in a patient with hemophilia B and oculocutaneous albinism.

Science.gov (United States)

O'Brien, Kevin J; Lozier, Jay; Cullinane, Andrew R; Osorio, Brigitte; Nghiem, Khanh; Speransky, Vladislav; Zein, Wadih M; Mullikin, James C; Neff, Anne T; Simon, Karen L; Malicdan, May Christine V; Gahl, William A; Young, Lisa R; Gochuico, Bernadette R

2016-11-01

Hemophilia B, an X-linked disease, manifests with recurrent soft tissue bleeding episodes. Hermansky-Pudlak syndrome, a rare autosomal recessive disorder, is characterized by oculocutaneous albinism and an increased tendency to bleed due to a platelet storage pool defect. We report a novel mutation in HPS6 in a Caucasian man with hemophilia B and oculocutaneous albinism. The patient was diagnosed with hemophilia B at age 4months due to recurrent soft tissue bleeding episodes, and he was also diagnosed with Hermansky-Pudlak syndrome at 32years of age due to unexplained oculocutaneous albinism. His factor IX level was markedly reduced at 13%; whole exome and Sanger sequencing showed the Durham mutation in F9 (NM_000133.3). The diagnosis of Hermansky-Pudlak syndrome subtype 6 was established by demonstrating absence of platelet delta granules on whole mount electron microscopy, an abnormal secondary wave in platelet aggregation studies, and a novel homozygous c.1114 C>T (p.Arg372*) mutation in HPS6 (NM_024747.5) on exome analysis and Sanger sequencing. Clinical phenotyping revealed no evidence of recurrent or unusual infections, interstitial lung disease or pulmonary fibrosis, or neurological disorders. The patient was treated with fresh frozen plasma, recombinant factor IX, and aminocaproic acid. Treatment with desmopressin was added to his regimen after he was diagnosed with Hermansky-Pudlak syndrome. Treatment of bleeding episodes results in effective hemostasis, and the patient has not required platelet or blood product transfusions. This report highlights the need to consider Hermansky-Pudlak syndrome as an etiology of oculocutaneous albinism even in patients with known hematologic disorders associated with bleeding. Identification of a novel mutation in HPS6 in an individual with hemophilia B shows that, although quite rare, patients may be diagnosed with two independent inherited bleeding disorders. No evidence of lung disease was found in this adult patient

Neonatal-onset hemophagocytic lymphohistiocytosis associated with primary dengue infection

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Madhumita Nandi

2016-01-01

Full Text Available A 40-day-old baby presented with prolonged fever, petechial spots, hepatosplenomegaly, generalized lymphadenopathy, and pancytopenia. Investigations revealed positive anti-dengue virus IgM antibody, and bone marrow examination demonstrated the presence of hemophagocytes. The diagnosis of hemophagocytic lymphohistiocytosis (HLH was made according to HLH-2004 guidelines. HLH associated with primary dengue in an infant who was symptomatic from neonatal age has hitherto not been reported in the literature.

Course and forecast of the hypothalamic pubertal syndrome

International Nuclear Information System (INIS)

Kayusheva, I.V.

1987-01-01

A total of 223 patients with the hypothalamic pubertal syndrome (HPS) were followed up for 1 to 22 years. The course of HPS was regressive, stable , recurrent or progressive and dependent on the initial depth and spread of hypothalamic lesion, repeated unfavourable hypothalamic exposures, and timely and regular treatment. HPS outcomes were followed up in 190 cases. The recovery was complete in 21.05%, obesity alone persisted in 10.53%, vegetovascular dystonia was persistent in 7.36%, and polycystic ovaries in 5.79%. Neuroendocrine hypothalamic syndrome was the most common (50.53%) HPS outcome. Hormone levels in blood were investigated using radioimmunoassay in patients with neuroendocrine form of HPS

Det hepatopulmonale syndrome

DEFF Research Database (Denmark)

Eibye, Simone; Christensen, Erik

2016-01-01

The hepatopulmonary syndrome (HPS) - a complication of liver disease - seems to be underdiagnosed, probably because of decreased awareness. HPS consists of the triade liver disease, intrapulmonary vascular dilatation and as a consequence arterial hypoxaemia. No medical therapy has proven effective...

Wolman disease in patients with familial hemophagocytic ...

African Journals Online (AJOL)

Solaf Elsayed

2015-09-26

Sep 26, 2015 ... Marine Gil b ... many inborn errors of metabolism and lysosomal storage diseases in which hemophagocytic ... The diagnosis of secondary HLH is usually made in association with infection by viruses, bacteria, fungi, or para-.

Serum Cytokine Profiles Differentiating Hemorrhagic Fever with Renal Syndrome and Hantavirus Pulmonary Syndrome

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Svetlana F. Khaiboullina

2017-05-01

Full Text Available Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome (HPS. HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21. In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

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Katherine Devitt

2014-01-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

Science.gov (United States)

Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2014-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

Wolman disease in patients with familial hemophagocytic ...

African Journals Online (AJOL)

Major signs and symptoms include hepatomegaly, splenomegaly, anemia, leucopenia or thrombocytopenias which resemble many inborn errors of metabolism and lysosomal storage diseases in which hemophagocytic lymphohistiocytosis has also been reported as a secondary association. Case reports: We report three ...

EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease

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John Jacob Kinross-Wright

2018-01-01

Full Text Available Background. Epstein-Barr virus- (EBV- associated lymphoproliferative disease (LPD is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. Case Summary. A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. Conclusion. To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry

OpenAIRE

Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M.; Luzzatto, Lucio; Aric?, Maurizio

2016-01-01

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. Objective This work aims to further our understanding of the pathogenic bases of this ra...

“Hemophagocytic Lymphohistiocytosis after EBV reactivation and ibrutinib treatment in relapsed/refractory Chronic Lymphocytic Leukemia”

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Maurizio Cavallari

2017-01-01

Full Text Available Hemophagocytic Lymphohistiocytosis (HLH is a rare syndrome characterized by ineffective T-cell and NK response. We report the clinical course of a patient with relapsed CLL who developed acute symptoms soon after starting ibrutinib. Hyperpyrexia, splenomegaly, hyperferritinemia, hypertriglyceridemia, cytopenias, and a typical cytokine pattern, i.e. high interleukin (IL−6, IL10 and IL18, were consistent with a diagnosis of HLH. Coexistent Epstein Barr virus reactivation was documented. Ibrutinib-induced impairment of NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency may have contributed to the development of HLH in our patient.

Searching for heavy photons in the HPS Experiment

Energy Technology Data Exchange (ETDEWEB)

Uemura, Sho [SLAC National Accelerator Lab., Menlo Park, CA (United States)

2016-11-01

The Heavy Photon Search (HPS) is a new experiment at Jefferson Lab that searches for a massive U(1) vector boson (known as a heavy photon or A′) in the MeV-GeV mass range and coupling weakly to ordinary matter through a kinetic mixing interaction. The HPS experiment seeks to produce heavy photons by electron bremsstrahlung on a fixed target, is sensitive to heavy photon decays to e+e-, and targets the range in heavy photon mass m_A' ~ 20 - 600 MeV, and kinetic mixing strength epsilon^2 ~ 10^-5 - 10^−10. HPS searches for heavy photons using two signatures: a narrow mass resonance and displaced vertices. This dissertation presents the theoretical and experimental motivations for a heavy photon, the design and operation of the HPS experiment, and the displaced vertex search. The data used in this dissertation is the unblinded fraction of the 2015 HPS run, for the period of operation where the HPS silicon vertex tracker (SVT) was operated at its nominal position. This data was recorded from May 13 to May 18, 2015, at a beam energy of 1.056 GeV and a nominal beam current of 50 nA. The integrated luminosity is 119 nb^-1, which is equivalent to 0.172 days of ideal running at the nominal beam current. This dissertation presents results (signal significance and upper limits) from the displaced vertex search in the mass range m_A' ~ 20 - 60 MeV, and kinetic mixing strength epsilon^2 ~ 2 × 10^-8 - 10^-10. This search does not have sufficient sensitivity to exclude a canonical heavy photon at any combination of m_A' and epsilon^2. The strictest limit achieved in this analysis on the production of a particle that decays like a heavy photon is 115 times the expected production cross-section for a heavy photon. Factors limiting the sensitivity of this analysis are discussed. Projections of HPSperformance with the full 2015 data set, and with planned improvements to theanalysis, are presented. Comparisons are also made to earlier reach estimates.

ANCA Vasculitis and Hemophagocytic Lymphohistiocytosis following a Fecal Microbiota Transplant

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Adam Amlani

2018-01-01

Full Text Available A 69-year-old female with antisynthetase syndrome, a history of multiple recurrent infections, and documented previous negative titres for anti-neutrophil cystoplasmic antibody (ANCA suddenly developed a de novo MPO-ANCA-associated glomerulonephritis three weeks after a fecal microbiota transplantation (FMT for recurrent Clostridium difficile infections. Six months following her FMT and less than two weeks following treatment for urosepsis, she developed severe cholestasis, a markedly elevated ferritin and hypertriglyceridemia. An initial liver biopsy was suggestive of drug-induced liver injury and thus she was treated with supportive care. After she failed to improve, a second liver biopsy supported the diagnosis of hemophagocytic lymphohistiocytosis (HLH. This case highlights difficulties surrounding the early diagnosis of HLH and also questions the role of FMT and/or recurrent infections as a trigger for ANCA-associated vasculitis.

Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism.

Science.gov (United States)

Dotta, Laura; Parolini, Silvia; Prandini, Alberto; Tabellini, Giovanna; Antolini, Maddalena; Kingsmore, Stephen F; Badolato, Raffaele

2013-10-17

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic

Pulmonary dysfunction and hepatopulmonary syndrome in cirrhosis and portal hypertension

DEFF Research Database (Denmark)

Møller, Søren; Krag, Aleksander; Madsen, Jan L

2009-01-01

BACKGROUND: Pulmonary dysfunction including the hepatopulmonary syndrome (HPS) is an important complication to cirrhosis and portal hypertension. However, the precise relation to liver dysfunction and the prevalence of HPS are unclear. AIMS: We therefore aimed to assess (i) the prevalence of HPS......, Pportal hypertension (post-sinusoidal resistance, P

Discovery of the Electronic Spectra of Hps and Dps

Science.gov (United States)

Grimminger, Robert A.; Wei, Jie; Ellis, Blaine; Clouthier, Dennis J.; Wang, Zhong; Sears, Trevor

2009-06-01

The hitherto unknown electronic spectrum of the closed shell transient molecule HPS has been observed in the 685 - 846 nm region by laser-induced fluorescence and single vibronic level emission techniques. HPS (and DPS) were produced in a pulsed electric discharge jet using a precursor mixture of 3% PH_3 and 1% H_2S (or PD_3 and D_2S) in high pressure argon. The weak set of observed bands are assigned to the à ^1A^''-X˜ ^1A^' electronic transition on the basis of chemical evidence, isotope shifts and the correspondence of the vibrational frequencies, excitation energy, and band contours with predictions based on our own high level ab initio calculations. Theory predicts that the HPS bond angle decreases on electronic excitation, contrary to expectations based on Walsh diagrams.

Epstein-Barr Virus (EBV-associated Haemophagocytic Syndrome

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Lorenza Torti

2012-01-01

Full Text Available We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS one month following acute infection caused by Epstein-Barr virus (EBV. Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection.

Diagnostic imaging of hypertrophic pyloric stenosis (HPS)

International Nuclear Information System (INIS)

Frkovic, M.; Seronja Kuhar, M.; Perhoc, Z.; Barbaric-Babic, V.; Molnar, M.; Vukovic, J.

2001-01-01

Background. Imaging of the abdomen in children with suspected hypertrophic pyloric stenosis has been traditionally performed by plain film radiography and upper gastrointestinal contrast studies. In many clinical situations, this approach has been modified or replaced by ultrasound examination. The authors aimed to analyse the value of diagnostic algorithm in children with hypertrophic pyloric stenosis confirmed at surgery in our hospital. Patients and methods. The authors made a five year retrospective review of hospital records of all children operated on for HPS in Clinical Hospital Centre Zagreb - Rebro and found out that 14 boys, between 2 (17 days) and 10 weeks of life (75 days) underwent surgery due to HPS. Results. Specific radiographic signs were: string sign, double track sign, elongation and narrowing of pyloric canal, mushroom sign, gastric distension with fluid and beak sign. Ultrasound was performed in 9 patients, one of them was false negative (sonographer admitted that he had no experience), the rest were positive. Conclusions. If the physical examination is negative or equivocal, sonography by an experienced sonographer must be performed. If the ultrasound finding is negative, than the infant should undergo to barium upper gastrointestinal studies (UGI). If HPS isn't a primary diagnostic question, it's better to perform UGI first in order to make a correct diagnosis. (author)

Presentation of hemophagocytic lymphohistiocytosis due to a novel MUNC 13–4 mutation masked by partial therapeutic immunosuppression

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Garrett Jackie P-D

2012-05-01

Full Text Available Abstract Hemophagocytic lymphohistiocytosis is a potentially fatal disease characterized by excessive macrophage and lymphocyte activity. Patients can be affected following immune activation after an oncologic, autoimmune or infectious trigger. An associated gene mutation may be found which impairs cytolytic lymphocyte function. We describe a pediatric case of hemophagocytic lymphohistiocytosis with a novel mutation of MUNC 13–4 whose diagnosis was confounded by concurrent immunosuppression. Clinical reassessment for hemophagocytic lymphohistiocytosis is necessary in persistently febrile patients with laboratory derangements in the setting of immunosuppressive agent exposure.

Epstein–Barr Virus and Hemophagocytic Lymphohistiocytosis

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Rebecca A. Marsh

2018-01-01

Full Text Available Epstein–Barr virus (EBV is a ubiquitous virus that infects nearly all people worldwide without serious sequela. However, for patients who have genetic diseases which predispose them to the development of hemophagocytic lymphohistiocytosis (HLH, EBV infection is a life-threatening problem. As a part of a themed collection of articles on EBV infection and human primary immune deficiencies, we will review key concepts related to the understanding and treatment of HLH.

Familial hemophagocytic lymphohistiocytosis in two Saudi siblings

OpenAIRE

Abbaker, Abdelakarim Ibrahim; Dammas, Ali Saeed

2015-01-01

Primary familial hemophagocytic lymphohistiocytosis (HLH; or familial erythrophagocytic lymphohistiocytosis [FEL]) is a heterogeneous autosomal recessive disorder more prevalent with parental consanguinity. There is aggressive proliferation of activated macrophages and histiocytes, which phagocytose red blood cells (RBCs), white blood cells (WBCs), and platelets, leading to anemia, neutropenia and thrombocytopenia. The exaggerated response of immune system in familial HLH can occur in the abs...

Hermansky-Pudlak syndrome: A case report

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R Vani

2014-01-01

Full Text Available Hermansky-Pudlak syndrome (HPS is a rare autosomal recessive disorder, which results in oculocutaneous albinism, bleeding disorders, and storage of abnormal fat protein compound (liposomal accumulation of ceroid lipofuscin. The major complications of this disorder are pulmonary fibrosis (PF and colitis. This is a case report of an HPS patient with PF.

Activities of HPS standards committee in environmental remediation

International Nuclear Information System (INIS)

Stencel, J.R.

1994-01-01

The Health Physics Society (HPS) develops American National Standards in the area of radiation protection using methods approved by the American National Standards Institute (ANSI). Two of its sections, Environmental Health Physics and Contamination Limits, have ongoing standards development which are important to some environmental remediation efforts. This paper describes the role of the HPS standards process and indicates particular standards under development which will be of interest to the reader. In addition, the authors solicit readers to participate in the voluntary standards process by either joining active working groups (WG) or suggesting appropriate and relevant topics which should be placed into the standards process

Large Scale Deployment of Electric Vehicles (EVs) and Heat Pumps (HPs) in the Nordic Region

DEFF Research Database (Denmark)

Liu, Zhaoxi; Wu, Qiuwei; Petersen, Pauli Fríðheim

This report describes the study results of large scale deployment of electric vehicles (EVs) and heat pumps (HPs) in the Nordic countries of Denmark, Norway, Sweden and Finland, focusing on the demand profiles with high peneration of EVs and HPs in 2050......This report describes the study results of large scale deployment of electric vehicles (EVs) and heat pumps (HPs) in the Nordic countries of Denmark, Norway, Sweden and Finland, focusing on the demand profiles with high peneration of EVs and HPs in 2050...

Typhoid Fever Complicated by Hemophagocytic Lymphohistiocytosis and Rhabdomyolysis.

Science.gov (United States)

Non, Lemuel R; Patel, Rupa; Esmaeeli, Amir; Despotovic, Vladimir

2015-11-01

Hemophagocytic lymphohistiocytosis (HLH) and rhabdomyolysis are rare complications of typhoid fever from Salmonella enterica serovar Typhi. Herein, we describe the clinical features in a 21-year-old female from India who presented to the intensive care unit with fever, severe pancytopenia, and rhabdomyolysis. © The American Society of Tropical Medicine and Hygiene.

Hemophagocytic lymphohistiocytosis: a rare diagnosis, an even rarer opportunity to appraise our understanding of the immune system

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José Alexandre Marzagão Barbuto

2015-03-01

Full Text Available The syndrome identified as hemophagocytic lymphohistiocytosis (HLH poses a rather difficult challenge to the physician. HLH was initially described as a familial disorder,1 which was later associated with various genetic defects that affect the cytotoxic machinery of CD8+ T and NK cells,2 but it also occurs sporadically, usually prompted by infections, rheumatic disorders, or neoplasia.3 Although its diagnostic criteria are established, its clinical presentation overlaps with many different conditions, requiring an enhanced awareness of the attending physician in order to reach the diagnosis and to initiate treatment early enough.

Simulation of the single-vibronic-level emission spectrum of HPS

Energy Technology Data Exchange (ETDEWEB)

Mok, Daniel K. W., E-mail: bcdaniel@polyu.edu.hk, E-mail: epl@soton.ac.uk; Chau, Foo-tim [Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom (Hong Kong); Lee, Edmond P. F., E-mail: bcdaniel@polyu.edu.hk, E-mail: epl@soton.ac.uk [Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom (Hong Kong); School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom); Dyke, John M. [School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom)

2014-05-21

We have computed the potential energy surfaces of the X{sup ~1}A{sup ′} and A{sup ~1}A{sup ′′} states of HPS using the explicitly correlated multi-reference configuration interaction (MRCI-F12) method, and Franck–Condon factors between the two states, which include anharmonicity and Duschinsky rotation, with the aim of testing the assignment of the recently reported single-vibronic-level (SVL) emission spectrum of HPS [R. Grimminger, D. J. Clouthier, R. Tarroni, Z. Wang, and T. J. Sears, J. Chem. Phys. 139, 174306 (2013)]. These are the highest level calculations on these states yet reported. It is concluded that our spectral simulation supports the assignments of the molecular carrier, the electronic states involved and the vibrational structure of the experimental laser induced fluorescence, and SVL emission spectra proposed by Grimminger et al. [J. Chem. Phys. 139, 174306 (2013)]. However, there remain questions unanswered regarding the relative electronic energies of the two states and the geometry of the excited state of HPS.

Simulation of the single-vibronic-level emission spectrum of HPS

International Nuclear Information System (INIS)

Mok, Daniel K. W.; Chau, Foo-tim; Lee, Edmond P. F.; Dyke, John M.

2014-01-01

We have computed the potential energy surfaces of the X ~1 A ′ and A ~1 A ′′ states of HPS using the explicitly correlated multi-reference configuration interaction (MRCI-F12) method, and Franck–Condon factors between the two states, which include anharmonicity and Duschinsky rotation, with the aim of testing the assignment of the recently reported single-vibronic-level (SVL) emission spectrum of HPS [R. Grimminger, D. J. Clouthier, R. Tarroni, Z. Wang, and T. J. Sears, J. Chem. Phys. 139, 174306 (2013)]. These are the highest level calculations on these states yet reported. It is concluded that our spectral simulation supports the assignments of the molecular carrier, the electronic states involved and the vibrational structure of the experimental laser induced fluorescence, and SVL emission spectra proposed by Grimminger et al. [J. Chem. Phys. 139, 174306 (2013)]. However, there remain questions unanswered regarding the relative electronic energies of the two states and the geometry of the excited state of HPS

Simulation of the single-vibronic-level emission spectrum of HPS.

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Mok, Daniel K W; Lee, Edmond P F; Chau, Foo-tim; Dyke, John M

2014-05-21

We have computed the potential energy surfaces of the X¹A' and ùA" states of HPS using the explicitly correlated multi-reference configuration interaction (MRCI-F12) method, and Franck-Condon factors between the two states, which include anharmonicity and Duschinsky rotation, with the aim of testing the assignment of the recently reported single-vibronic-level (SVL) emission spectrum of HPS [R. Grimminger, D. J. Clouthier, R. Tarroni, Z. Wang, and T. J. Sears, J. Chem. Phys. 139, 174306 (2013)]. These are the highest level calculations on these states yet reported. It is concluded that our spectral simulation supports the assignments of the molecular carrier, the electronic states involved and the vibrational structure of the experimental laser induced fluorescence, and SVL emission spectra proposed by Grimminger et al. [J. Chem. Phys. 139, 174306 (2013)]. However, there remain questions unanswered regarding the relative electronic energies of the two states and the geometry of the excited state of HPS.

T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

Science.gov (United States)

2017-08-29

Acute Lymphoblastic Leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hemophagocytic Lymphohistiocytosis (HLH); Familial Hemophagocytic Lymphohistiocytosis (FLH); Viral-associated Hemophagocytic Syndrome (VAHS); X-linked Lymphoproliferative Disease (XLP)

Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin

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Gahl William A

2005-09-01

Full Text Available Abstract Background Hermansky-Pudlak syndrome (HPS is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3 results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE at residues 172–176. Results Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. Conclusion HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

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Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M; Luzzatto, Lucio; Aricò, Maurizio

2016-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. From our registry, we have analyzed a total of 500 unselected patients with HLH. Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Protective effect of tanshinol on the hepatopulmonary syndrome in rat].

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Jia, Jian-Tao; Zhang, Hui-Ying; Lai, Li-Na; Li, Xu-Jiong; Tian, Xiao-Xia; Zhang, Li-Li; Lv, Min-Li; Zhao, Zhong-Fu; Han, De-Wu; Cheng, Ji

2014-05-01

To explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS). SD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively. Thickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group. Tanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.

Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2

DEFF Research Database (Denmark)

Meeths, Marie; Entesarian, Miriam; Al-Herz, Waleed

2010-01-01

Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells...... (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell......-associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical...

Hantavirus Pulmonary Syndrome in the United States.

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Fabbri, Marilyn; Maslow, Melanie J.

2001-06-01

Since the first outbreak of hantavirus pulmonary syndrome (HPS) in 1993, understanding of the vast distribution and potential impact of hantaviruses has grown. At least 277 cases of HPS have been documented in the United States. The full clinical spectrum has yet to be elucidated, and one outbreak suggested the possibility of person-to-person transmission. New research has identified the b-3 integrins as cellular receptors for hantaviruses and has determined the pivotal role of the immune system in pathogenesis. Rapid diagnosis has been facilitated by a new immunoblot assay to detect Sin Nombre virus infection. Treatment remains primarily supportive; however, a placebo- controlled trial of ribavirin is ongoing. Extracorporeal membrane oxygenation may be a potential therapy in severe cases; inhaled nitric oxide needs further study. Vaccines developed against hantaviruses associated with hemorrhagic fever and renal syndrome might be effective against HPS-associated strains.

Hermansky-Pudlak syndrome in a pregnant patient: a case report.

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Harris-Glocker, Miranda; Thornburg, Loralei L; Pressman, Eva K

2013-01-01

Hermansky-Pudlak syndrome (HPS), a rare autosomal-recessive disorder encompassing multiple organs, is characterized by oculocutaneous albinism, platelet storage pool deficiency resulting in bleeding diathesis, and ceroid lipofuscin deposition which can lead to pulmonary fibrosis, colitis, cardiomyopathy and renal failure. Pregnancy in a patient with HPS can produce multiple complications such as peripartum hemorrhage and difficulties with administration of anesthesia, either regional or general. We present the case of a patient with HPS also complicated by spontaneous triplet pregnancy. A multidisciplinary approach, including the involvement of obstetric, anesthesia, and hematology teams, is the ideal for an HPS patient with the potential for multiple complications in the peripartum period.

ARE THE SPIDER ANGIOMAS SKIN MARKERS OF HEPATOPULMONARY SYNDROME?

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Americo de Oliveira SILVERIO

2013-09-01

Full Text Available Context Hepatopathies can significantly influence both veins and arteries, these changes may cause some cutaneous stigmas, such as spider angioma (SA and some systemic vascular changes, such as those observed in hepatopulmonary syndrome (HPS. Based on this common pathophysiological root we can assume that the SA can be skin markers of HPS. Objective The objective of this study is to assess whether there is a relationship between the presence of SA and HPS. Methods Records of 40 patients with liver cirrhosis who underwent contrast echocardiography were evaluated, in which we researched the description of SA, physical examination, and other clinical and laboratory data. For diagnosis of HPS we use these signs of the disease: presence of liver disease (cirrhosis in the case, abnormalities in gas exchange by arterial blood gases, and evidence of pulmonary vasodilations by the contrast echocardiography. Results The SA were found in 21/40 (52.5% patients and hepatopulmonary syndrome in 9/40 (22.5%. The HPS was observed in 8/21 (38.1% of patients with SA and 1/19 (5.3% patients were without this sign (P<0.01. We found no statistically significant difference between the SA and the presence of HPS with sex or age. Patients with SA had a higher hypoxemia [PaO2 84.8 ± 11.5 mmHg and 19.8 ± 14.7 mmHg alveolar-arterial gradient of oxygen (AAG] than those without SA (PaO2 90.8 ± 10.7 mmHg and 10.9 ± 11.7 AAG mmHg (P<0.05. Conclusion Our findings show a correlation between the presence of SA and HPS, suggesting that the SA may be cutaneous markers of HPS.

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

NARCIS (Netherlands)

Boparai, K. S.; Reitsma, J. B.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.

2010-01-01

Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

NARCIS (Netherlands)

Boparai, K.S.; Reitsma, J.B.; Lemmens, V.; Os, T.A. van; Mathus-Vliegen, E.M.H.; Koornstra, J.J.; Nagengast, F.M.; Hest, L.P. van; Keller, J.J.; Dekker, E. den

2010-01-01

INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

NARCIS (Netherlands)

Boparai, K. S.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.; Reitsma, J.

Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Imaging characteristics of hemophagocytic lymphohistiocytosis

International Nuclear Information System (INIS)

Fitzgerald, Nancy E.; MacClain, Kenneth L.

2003-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma. (orig.)

Imaging characteristics of hemophagocytic lymphohistiocytosis

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Fitzgerald, Nancy E. [E. B. Singleton Department of Diagnostic Imaging, Texas Children' s Hospital, 6621 Fannin Street, MC 2-2521, TX 77030, Houston (United States); MacClain, Kenneth L. [Texas Children' s Cancer Center, 6701 Fannin, Suite 1510, TX 77030, Houston (United States)

2003-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma. (orig.)

Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

NARCIS (Netherlands)

Hengst, M. (Meike); Naehrlich, L. (Lutz); P. Mahavadi (Poornima); Grosse-Onnebrink, J. (Joerg); Terheggen-Lagro, S. (Suzanne); Skanke, L.Hø. (Lars Høsøien); Schuch, L.A. (Luise A.); Brasch, F. (Frank); A. Guenther (Andreas); S. Reu (Simone); Ley-Zaporozhan, J. (Julia); Griese, M. (Matthias)

2018-01-01

textabstractBackground: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in

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....

Hemophagocytic Lymphohistiocytosis in Children: Pathogenesis and Treatment

Science.gov (United States)

Ishii, Eiichi

2016-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder in children that is characterized by persistent fever, splenomegaly with cytopenia, hypertriglyceridemia, and hypofibrinogenemia. Increased levels of various cytokines and soluble interleukin-2 receptor are biological markers of HLH. HLH can be classified into two major forms: primary and secondary. Familial hemophagocytic lymphohistiocytosis (FHL), a type of primary HLH, is an autosomal recessive disorder that typically occurs in infancy and can be classified into five different subtypes (FHL types 1–5). In Japan, >80% of patients with FHL have either PRF1 (FHL type 2) or UNC13D (FHL type 3) defects. FHL is considered to be a disorder of T-cell function because the activity of NK cells or cytotoxic T lymphocytes as target cells is usually impaired. Moreover, Epstein–Barr virus-associated HLH (EBV-HLH) is considered a major subtype of secondary HLH. Any genetic background could have an effect on the pathogenesis of secondary HLH because EBV-HLH is considered to be particularly prevalent in Asian countries. For primary HLH, hematopoietic stem cell transplantation is the only accepted curative therapy, although cord blood transplantation with a reduced-conditioning regimen has been used with superior outcomes. For secondary HLH, including EBV-HLH, immunochemotherapy based on the HLH-2004 protocol has been used. In the near future, the entire mechanism of HLH should be clarified to establish less toxic therapies, including cell therapy and gene targeting therapy. PMID:27242976

Optimal Operation of EVs and HPs in the Nordic Power System

DEFF Research Database (Denmark)

Liu, Zhaoxi

penetration level in the market environment. • The feasibility investigation of EVs and HPs to provide frequency reserves to the Nordic power system. To accomplish the researches mentioned above, the driving patterns of the vehicles in the Nordic region and the impacts of the EV and HP demand on the day...... that both EVs and HPs can provide considerable frequency reserves to the power system along the day in the Nordic region. Vehicle-to-Grid (V2G) technologies which enable the EVs to discharge the batteries in the reserve operations can further utilize the capacity of the EVs and consequently increase...

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

Science.gov (United States)

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Anaplasma phagocytophilum-Related Defects in CD8, NKT, and NK Lymphocyte Cytotoxicity

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Diana G. Scorpio

2018-04-01

Full Text Available Human granulocytic anaplasmosis, caused by the tick-transmitted Anaplasma phagocytophilum, is not controlled by innate immunity, and induces a proinflammatory disease state with innate immune cell activation. In A. phagocytophilum murine infection models, hepatic injury occurs with production of IFNγ thought to be derived from NK, NKT cells, and CD8 T lymphocytes. Specific A. phagocytophilum ligands that drive inflammation and disease are not known, but suggest a clinical and pathophysiologic basis strikingly like macrophage activation syndrome (MAS and hemophagocytic syndrome (HPS. We studied in vivo responses of NK, NKT, and CD8 T lymphocytes from infected animals for correlates of lymphocyte-mediated cytotoxicity and examined in vitro interactions with A. phagocytophilum-loaded antigen-presenting cells (APCs. Murine splenocytes were examined and found deficient in cytotoxicity as determined by CD107a expression in vitro for specific CTL effector subsets as determined by flow cytometry. Moreover, A. phagocytophilum-loaded APCs did not lead to IFNγ production among CTLs in vitro. These findings support the concept of impaired cytotoxicity with A. phagocytophilum presentation by APCs that express MHC class I and that interact with innate and adaptive immune cells with or after infection. The findings strengthen the concept of an enhanced proinflammatory phenotype, such as MAS and HPS disease states as the basis of disease and severity with A. phagocytophilum infection, and perhaps by other obligate intracellular bacteria.

Iatrogenic T-Cell Lymphoma with Associated Hemophagocytic Lymphohistiocyotsis in a Patient with Long-Standing Rheumatoid Arthritis

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X. A. Andrade

2018-01-01

Full Text Available Patients with rheumatoid arthritis are at increased risk of hematological malignancies, especially when exposed to immunosuppressive therapy. The mechanisms of lymphomagenesis remain poorly understood but factors implicated include high disease activity, exposure to antitumoral necrosis factor medications, and Epstein–Barr virus infection. Lymphoid malignancies of T-cell origin are uncommon in patients with rheumatoid arthirits. Clinical presentation with associated hemophagocytic lymphohistiocyotsis is rare and confers a poor prognosis. This case report illustrates a case of a patient with long-standing rheumatoid arthritis and an iatrogenic peripheral T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis who achieved a complete response after intensive chemotherapy.

Hantavirus Pulmonary Syndrome in Argentina, 1995–2008

Science.gov (United States)

Bellomo, Carla M.; Cacace, María Luisa; Suárez, Paola; Bogni, Liliana; Padula, Paula J.

2010-01-01

We report a large case series of hantavirus pulmonary syndrome (HPS) in Argentina that was confirmed by laboratory restuls from 1995 through 2008. The geographic and temporal distribution of cases by age, sex, fatality rate, and risk factors for HPS was analyzed. A total of 710 cases were unequally distributed among 4 of the 5 Argentine regions. Different case-fatality rates were observed for each affected region, with a maximum rate of 40.5%. The male-to-female ratio for HPS case-patients was 3.7:1.0; the case-fatality rate was significantly higher for women. Agriculture-associated activities were most commonly reported as potential risk factors, especially among men of working age. Although HPS cases occurred predominantly in isolation, we identified 15 clusters in which strong relationships were observed between members, which suggests ongoing but limited person-to-person transmission. PMID:21122213

Increased polyp detection using narrow band imaging compared with high resolution endoscopy in patients with hyperplastic polyposis syndrome

NARCIS (Netherlands)

Boparai, K. S.; van den Broek, F. J. C.; van Eeden, S.; Fockens, P.; Dekker, E.

2011-01-01

Hyperplastic polyposis syndrome (HPS) is associated with colorectal cancer and is characterized by multiple hyperplastic polyps, sessile serrated adenomas (SSAs) and adenomas. Narrow band imaging (NBI) may improve the detection of polyps in HPS. We aimed to compare polyp miss rates with NBI with

[Hepatopulmonary syndrome and portopulmonary hypertension].

Science.gov (United States)

Marcu, Cristina; Schiffer, Eduardo; Aubert, John-David; Vionnet, Julien; Yerly, Patrick; Deltenre, Pierre; Marot, Astrid

2017-08-30

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates.

An unusual presentation of galactosemia: Hemophagocytic lymphohistiocytosis

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Ahmet Afşin Kundak

2012-12-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a rare life-threatening condition. Uncontrolled proliferation of activated lymphocytes secreting high amounts of inflammatory cytokines seems to be the main pathogenesis. The diagnosis of HLH can often be difficult. It may presents in many forms such as fever of unknown origin, hepatitis, acute liver failure, and sepsis-like illness. Here we present a newborn galactosemia case presented with HLH. Close monitoring of the diagnostic criteria of HLH during the course of galactosemia-associated hemophagocytosis, both before and after dietary treatment, should be performed in order to fully determine if the triggering mechanism is infection or accumulation of metabolites.

HPS: A space fission power system suitable for near-term, low-cost lunar and planetary bases

International Nuclear Information System (INIS)

Houts, M.G.; Poston, D.I.; Ranken, W.A.

1996-01-01

Near-term, low-cost space fission power systems can enhance the feasibility and utility of lunar and planetary bases. One such system, the Heatpipe Power System (HPS), is described in this paper. The HPS draws on 40 yr of United States and international experience to enable a system that can be developed in <5 yr at a cost of <$100M. Total HPS mass is <600 kg at 5 kWe and <2000 kg at 50 kWe, assuming that thermoelectric power conversion is used. More advanced power conversion systems could reduce system mass significantly. System mass for planetary surface systems also may be reduced (1) if indigenous material is used for radiation shielding and (2) because of the positive effect of the gravitational field on heatpipe operation. The HPS is virtually non-radioactive at launch and is passively subcritical during all credible launch accidents. Full-system electrically heated testing is possible, and a ground nuclear power test is not needed for flight qualification. Fuel burnup limits are not reached for several decades, thus giving the system long-life potential

Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter syndrome

DEFF Research Database (Denmark)

Nüsing, Rolf M; Treude, Antje; Weissenberger, Christian

2005-01-01

Increased formation of prostaglandin E2 (PGE2) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition of PGE2 formation by cyclo-oxygenase inhibitors significantly lowers patient...

Spontaneous Escherichia coli Meningitis Associated with Hemophagocytic Lymphohistiocytosis

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Kuo-Hsuan Chang

2006-01-01

Full Text Available Spontaneous Escherichia coli meningitis has not been previously reported in association with hemophago-cytic lymphohistiocytosis (HLH. A previously healthy 72-year-old woman was admitted due to fever, nuchal rigidity, disturbed consciousness and splenomegaly. Anemia, thrombocytopenia and hyperfer-ritinemia developed on the 8th day of hospitalization. Cultures of cerebrospinal fluid and blood grew E. coli. Abundant macrophages overwhelmed erythrocytes in the bone marrow aspirate, confirming the presence of hemophagocytosis. E. coli meningitis was managed with a 40-day course of antibiotic treatment. However, the severity of anemia and thrombocytopenia progressed despite intensive transfusion therapy. The patient died of HLH on the 60th day of hospitalization.

Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation.

Science.gov (United States)

Pascasio, J M; Grilo, I; López-Pardo, F J; Ortega-Ruiz, F; Tirado, J L; Sousa, J M; Rodriguez-Puras, M J; Ferrer, M T; Sayago, M; Gómez-Bravo, M A; Grilo, A

2014-06-01

The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Successful resolution of severe hepatopulmonary syndrome following liver transplantation.

Science.gov (United States)

Asthana, Sonal; Maguire, Connor; Lou, Lawrence; Meier, Michael; Bain, Vincent; Townsend, Derek R; Townsend, Rex; Lien, Dale; Bigam, David; Kneteman, Norman; Shapiro, Andrew Mark James

2010-04-01

Hepatopulmonary syndrome (HPS) is a complication of portal hypertension, defined by the presence of liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations producing a right-to-left intrapulmonary shunt. Liver transplantation (LT) is the treatment of choice; however, severe hypoxemia (PaO(2) < 50 mmHg on room air) is considered a contraindication to LT. This approach disadvantages some patients, particularly young patients with no intrinsic cardio-respiratory disease. We discuss one such patient who improved with LT despite having extremely severe HPS (PaO2 < 29 mmHg).

The role of perfusion computed tomography in the prediction of cerebral hyperperfusion syndrome.

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Chien Hung Chang

Full Text Available Hyperperfusion syndrome (HPS following carotid angioplasty with stenting (CAS is associated with significant morbidity and mortality. At present, there are no reliable parameters to predict HPS. The aim of this study was to clarify whether perfusion computed tomography (CT is a feasible and reliable tool in predicting HPS after CAS.We performed a retrospective case-control study of 54 patients (11 HPS patients and 43 non-HPS with unilateral severe stenosis of the carotid artery who underwent CAS. We compared the prevalence of vascular risk factors and perfusion CT parameters including regional cerebral blood volume (rCBV, regional cerebral blood flow (rCBF, and time to peak (TTP within seven days prior to CAS. Demographic information, risk factors for atherosclerosis, and perfusion CT parameters were evaluated by multivariable logistic regression analysis. The rCBV index was calculated as [(ipsilateral rCBV - contralateral rCBV/contralateral rCBV], and indices of rCBF and TTP were similarly calculated. We found that eleven patients had HPS, including five with intracranial hemorrhages (ICHs of whom three died. After a comparison with non-HPS control subjects, independent predictors of HPS included the severity of ipsilateral carotid artery stenosis, 3-hour mean systolic blood pressure (3 h SBP after CAS, pre-stenting rCBV index >0.15 and TTP index >0.22.The combination of severe ipsilateral carotid stenosis, 3 h SBP after CAS, rCBV index and TTP index provides a potential screening tool for predicting HPS in patients with unilateral carotid stenosis receiving CAS. In addition, adequate management of post-stenting blood pressure is the most important treatable factor in preventing HPS in these high risk patients.

Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

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Senthilkumar Sankararaman

2014-01-01

Full Text Available X-linked lymphoproliferative disease (XLP is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV. EBV-induced hemophagocytic lymphohistiocytosis (HLH is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP.

Superplasticity of Inconel 718 after processing by high-pressure sliding (HPS)

Czech Academy of Sciences Publication Activity Database

Takizawa, Y.; Kajita, T.; Král, Petr; Masuda, T.; Watanabe, K.; Yumoto, M.; Otagiri, Y.; Sklenička, Václav; Horita, Z.

2017-01-01

Roč. 682, JAN (2017), s. 603-612 ISSN 0921-5093 Institutional support: RVO:68081723 Keywords : High-pressure sliding (HPS) * Severe plastic deformation (SPD) * Ni-based superalloy * Superplasticity * Grain boundary sliding * Lattice diffusion Subject RIV: JG - Metallurgy OBOR OECD: Materials engineering Impact factor: 3.094, year: 2016

Hemophagocytic lymphohistiocytosis and Pelger-Huët anomaly associated with colchicine intoxication

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Baris Malbora

2014-06-01

Full Text Available Colchicine is frequently used in the treatment of familial Mediterranean fever (FMF. First symptoms of colchicine intoxication are gastrointestinal disturbances, such as abdominal cramps, diarrhea, pancytopenia and so on. Herein, we report a female FMF patient with pancytopenia and hemophagocytic lymphohitiocytosis (HLH, following colchicine intoxication for committing suicide. To our knowledge, this is the first reported case of a patient with HLH associated with colchicine intoxication.

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

Sonke, Gabe S.; Ludwig, Inge; van Oosten, Hannah; Baars, Joke W.; Meijer, Ellen; Kater, Arnon P.; de Jong, Daphne

2008-01-01

Chronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus associated hemophagocytic lymphohistiocytosis. These 2 abnormal

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

NARCIS (Netherlands)

G.S. Sonke (Gabe); I. Ludwig (Inge); H. van Oosten (Hannah); J.W. Baars (Joke); E. Meijer (Ellen); A.P. Kater (Arnon); D. de Jong (Daphne)

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2

High Level of Perforin Expression Is Required for Effective Correction of Hemophagocytic Lymphohistiocytosis

OpenAIRE

Tiwari, Swati; Hontz, Adrianne; Terrell, Catherine E.; Arumugam, Paritha; Carmo, Marlene; Risma, Kimberly; Jordan, Michael; Malik, Punam

2016-01-01

Perforin-1 mutations result in a potentially fatal hemophagocytic lymphohistiocytosis (HLH) with heightened immune activation, hypercytokinemia, pancytopenia, and end-organ damage. At present, hematopoietic stem cell (HSC) transplantation is curative, but limited by donor availability and associated mortality, making gene therapy an attractive alternative approach for HLH. We reported that perforin expression driven by cellular promoters in lentiviral (LV) vectors resulted in significant, alb...

Germline heterozygous variants in genes associated with familial hemophagocytic lymphohistiocytosis as a cause of increased bleeding

DEFF Research Database (Denmark)

Fager Ferrari, Marcus; Leinoe, Eva; Rossing, Maria

2018-01-01

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by biallelic variants in genes regulating granule secretion in cytotoxic lymphocytes. In FHL3-5, the affected genes UNC13D, STX11 and STXBP2 have further been shown to regulate the secretion of platelet granules, giving rise to compromised...

HPS instrument calibration laboratory accreditation program

Energy Technology Data Exchange (ETDEWEB)

Masse, F.X; Eisenhower, E.H.; Swinth, K.L.

1993-12-31

The purpose of this paper is to provide an accurate overview of the development and structure of the program established by the Health Physics Society (HPS) for accrediting instrument calibration laboratories relative to their ability to accurately calibrate portable health physics instrumentation. The purpose of the program is to provide radiation protection professionals more meaningful direct and indirect access to the National Institute of Standards and Technology (NIST) national standards, thus introducing a means for improving the uniformity, accuracy, and quality of ionizing radiation field measurements. The process is designed to recognize and document the continuing capability of each accredited laboratory to accurately perform instrument calibration. There is no intent to monitor the laboratory to the extent that each calibration can be guaranteed by the program; this responsibility rests solely with the accredited laboratory.

Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky–Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico

Science.gov (United States)

Santiago Borrero, Pedro J.; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y.; Izquierdo, Natalio J.; del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A.; Cadilla, Carmen L.

2013-01-01

Hermansky–Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of ~1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population. PMID:16417222

Immunophenotypic and Ultrastructural Analysis of Mast Cells in Hermansky-Pudlak Syndrome Type-1: A Possible Connection to Pulmonary Fibrosis.

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Arnold S Kirshenbaum

Full Text Available Hermansky-Pudlak Syndrome type-1 (HPS-1 is an autosomal recessive disorder caused by mutations in HPS1 which result in reduced expression of the HPS-1 protein, defective lysosome-related organelle (LRO transport and absence of platelet delta granules. Patients with HPS-1 exhibit oculocutaneous albinism, colitis, bleeding and pulmonary fibrosis postulated to result from a dysregulated immune response. The effect of the HPS1 mutation on human mast cells (HuMCs is unknown. Since HuMC granules classify as LROs along with platelet granules and melanosomes, we set out to determine if HPS-1 cutaneous and CD34+ culture-derived HuMCs have distinct granular and cellular characteristics. Cutaneous and cultured CD34+-derived HuMCs from HPS-1 patients were compared with normal cutaneous and control HuMCs, respectively, for any morphological and functional differences. One cytokine-independent HPS-1 culture was expanded, cloned, designated the HP proMastocyte (HPM cell line and characterized. HPS-1 and idiopathic pulmonary fibrosis (IPF alveolar interstitium showed numerous HuMCs; HPS-1 dermal mast cells exhibited abnormal granules when compared to healthy controls. HPS-1 HuMCs showed increased CD63, CD203c and reduced mediator release following FcɛRI aggregation when compared with normal HuMCs. HPM cells also had the duplication defect, expressed FcɛRI and intracytoplasmic proteases and exhibited less mediator release following FcɛRI aggregation. HPM cells constitutively released IL-6, which was elevated in patients' serum, in addition to IL-8, fibronectin-1 (FN-1 and galectin-3 (LGALS3. Transduction with HPS1 rescued the abnormal HPM morphology, cytokine and matrix secretion. Microarray analysis of HPS-1 HuMCs and non-transduced HPM cells confirmed upregulation of differentially expressed genes involved in fibrogenesis and degranulation. Cultured HPS-1 HuMCs appear activated as evidenced by surface activation marker expression, a decrease in mediator

Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy

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R Rajyalakshmi

2016-01-01

Full Text Available Griscelli syndrome (GS is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, RAB27A (GS2, and MLPH (GS3 genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.

High-resolution computed tomography findings in eight patients with hantavirus pulmonary syndrome

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Barbosa, Diego de Lacerda; Hochhegger, Bruno; Souza Junior, Arthur Soares; Zanetti, Glaucia; Escuissato, Dante Luiz; Meirelles, Gustavo de Souza Portes; Funari, Marcelo Buarque de Gusmao; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Santa Casa de Porto Alegre, Porto Alegre, RS (Brazil); Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil); Ultra X, Sao Jose do Rio Preto, SP (Brazil); Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil); Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP (Brazil); Grupo Fleury, Sao Paulo, SP (Brazil); Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Faculdade de Medicina

2017-05-15

Objective: The purpose of this study was to describe the high-resolution computed tomography (HRCT) findings in patients with hantavirus pulmonary syndrome (HPS). Materials and Methods: We retrospectively reviewed HRCT findings from eight cases of HPS. All patients were men, aged 19-70 (mean, 41.7) years. Diagnoses were established by serological test (enzyme-linked immunosorbent assay) in all patients. Two chest radiologists analyzed the images and reached decisions by consensus. Results: The predominant HRCT findings were ground-glass opacities (GGOs) and smooth inter- and intralobular septal thickening, found in all eight cases; however, the crazy-paving pattern was found in only three cases. Pleural effusion and peribronchovascular thickening were observed in five patients. The abnormalities were bilateral in all patients. Conclusion: The predominant HRCT findings in patients with HPS were GGOs and smooth inter- and intralobular septal thickening, which probably correlate with the histopathologic findings of pulmonary edema. (author)

High-resolution computed tomography findings in eight patients with hantavirus pulmonary syndrome

International Nuclear Information System (INIS)

Barbosa, Diego de Lacerda; Hochhegger, Bruno; Souza Junior, Arthur Soares; Zanetti, Glaucia; Escuissato, Dante Luiz; Meirelles, Gustavo de Souza Portes; Funari, Marcelo Buarque de Gusmao; Marchiori, Edson; Santa Casa de Porto Alegre, Porto Alegre, RS; Faculdade de Medicina de Sao Jose do Rio Preto; Ultra X, Sao Jose do Rio Preto, SP; Universidade Federal do Parana; Universidade Federal de Sao Paulo; Grupo Fleury, Sao Paulo, SP; Universidade de Sao Paulo

2017-01-01

Objective: The purpose of this study was to describe the high-resolution computed tomography (HRCT) findings in patients with hantavirus pulmonary syndrome (HPS). Materials and Methods: We retrospectively reviewed HRCT findings from eight cases of HPS. All patients were men, aged 19-70 (mean, 41.7) years. Diagnoses were established by serological test (enzyme-linked immunosorbent assay) in all patients. Two chest radiologists analyzed the images and reached decisions by consensus. Results: The predominant HRCT findings were ground-glass opacities (GGOs) and smooth inter- and intralobular septal thickening, found in all eight cases; however, the crazy-paving pattern was found in only three cases. Pleural effusion and peribronchovascular thickening were observed in five patients. The abnormalities were bilateral in all patients. Conclusion: The predominant HRCT findings in patients with HPS were GGOs and smooth inter- and intralobular septal thickening, which probably correlate with the histopathologic findings of pulmonary edema. (author)

BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor.

Science.gov (United States)

Gerondopoulos, Andreas; Langemeyer, Lars; Liang, Jin-Rui; Linford, Andrea; Barr, Francis A

2012-11-20

Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting. These symptoms are caused by defects in the biogenesis of melanosomes and platelet dense granules, often referred to as lysosome-related organelles. Genes mutated in HPS encode subunits of the biogenesis of lysosome-related organelles complexes (BLOCs). BLOC-1 and BLOC-2, together with the AP-3 clathrin adaptor complex, act at early endosomes to sort components required for melanin formation and melanosome biogenesis away from the degradative lysosomal pathway toward early stage melanosomes. However the molecular functions of the Hps1-Hps4 complex BLOC-3 remain mysterious. Like other trafficking pathways, melanosome biogenesis and transport of enzymes involved in pigmentation involves specific Rab GTPases, in this instance Rab32 and Rab38. We now demonstrate that BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor (GEF). Silencing of the BLOC-3 subunits Hps1 and Hps4 results in the mislocalization of Rab32 and Rab38 and reduction in pigmentation. In addition, we show that BLOC-3 can promote specific membrane recruitment of Rab32/38. BLOC-3 therefore defines a novel Rab GEF family with a specific function in the biogenesis of lysosome-related organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

Science.gov (United States)

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Application of Wireless Intelligent Control System for HPS Lamps and LEDs Combined Illumination in Road Tunnel

Science.gov (United States)

Lai, Jinxing; Qiu, Junling; Chen, Jianxun; Wang, Yaqiong; Fan, Haobo

2014-01-01

Because of the particularity of the environment in the tunnel, the rational tunnel illumination system should be developed, so as to optimize the tunnel environment. Considering the high cost of traditional tunnel illumination system with high-pressure sodium (HPS) lamps as well as the effect of a single light source on tunnel entrance, the energy-saving illumination system with HPS lamps and LEDs combined illumination in road tunnel, which could make full use of these two kinds of lamps, was proposed. The wireless intelligent control system based on HPS lamps and LEDs combined illumination and microcontrol unit (MCU) Si1000 wireless communication technology was designed. And the remote monitoring, wireless communication, and PWM dimming module of this system were designed emphatically. Intensity detector and vehicle flow detector can be configured in wireless intelligent control system, which gather the information to the master control unit, and then the information is sent to the monitoring center through the Ethernet. The control strategies are got by the monitoring center according to the calculated results, and the control unit wirelessly sends parameters to lamps, which adjust the luminance of each segment of the tunnel and realize the wireless intelligent control of combined illumination in road tunnel. PMID:25587266

CLINICAL CASE OF TOCILIZUMAB THERAPY IN A PATIENT WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

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E. I. Alexeeva

2013-01-01

Full Text Available The article presents a case of successful application of a monoclonal antibodies drug to interleukin 6 receptors (tocilizumab at severe systemic juvenile idiopathic arthritis with the development of secondary hemophagocytic syndrome. Tocilizumab treatment secured a decrease in clinical and laboratory parameters of the disease activity, life quality improvement, systemic juvenile idiopathic arthritis and hemophagocytic syndrome remission and allowed avoiding the per os prescription of glucocorticoids.

Report of seven children with hepatopulmonary syndrome.

Science.gov (United States)

Erge, Duygu; Selimoğlu, Mukadder Ayşe; Karakurt, Cemşit; Karabiber, Hamza; Elkıran, Özlem; Çatal, Ferat; Koroğlu, Reyhan

2014-12-01

Hepatopulmonary syndrome is an important pulmonary vascular complication of liver disease. Its diagnosis is based on the presence of hypoxaemia and the demonstration of intrapulmonary shunting by contrast-enhanced echocardiography or perfusion lung scanning. Awareness of this condition is critical to improve the outcomes of patients with chronic liver disease and/or portal hypertension because hepatopulmonary syndrome receives additional priority on the waiting list for transplantation. A non-invasive measurement of the blood oxygen saturation with pulse oximetry is recommended as a screening tool for this syndrome. The aim of this report was to present clinical and laboratory findings and follow-up of seven paediatric patients who were diagnosed with HPS at our centre.

Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

Science.gov (United States)

Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

2018-05-01

Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.

Endoperoxidation, hyperprostaglandinemia, and hyperlipidemia in a case of erythrophagocytic lymphohistiocytosis. Reversal with VP-16 and indomethacin.

Science.gov (United States)

Brown, R E; Bowman, W P; D'Cruz, C A; Pick, T E; Champion, J E

1987-11-15

Clinicopathologic and histopathologic evidence of both endoperoxidation with hyperprostaglandinemia and hyperlipidemia in a 5-week-old infant with a hemophagocytic syndrome is reported. Institution of histiocytolytic (VP-16) and cyclo-oxygenase inhibitor (indomethacin) therapies returned the prostaglandin levels and lipid profile to a nearly normal state coincidental with clinical recovery. It appears that by reducing the cell mass of histiocytes and controlling the over-production of prostaglandins, some types of hemophagocytic syndrome can be reversed.

Reactive hemophagocytic syndromes in children with rheumatic diseases

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Piotr Gietka

2011-04-01

Full Text Available Reactive haemophagocytic syndrome (RHPS, also calledmacrophage activation syndrome (MAS, is a serious complicationof viral, rheumatic and malignant diseases, thought to be causedby the excessive activation of T lymphocytes and macrophages.MAS is characterized by polyorgan involvement with typical features:non-remitting fever, hepatic enlargement, considerable loweringof blood cell count and erythrocyte sedimentation rate (ESR,elevation of serum glutamic-oxaloacetic transaminase (SGOT,serum glutamic pyruvic transaminase (SGPT, lactate dehydrogenase(LDH and serum ferritin level, with hypofibrinogenemia. Themost characteristic feature is the presence of well differentiatedmacrophages, revealing an active haemophagocytosis in the bonemarrow aspirate. Because of rapid progression and fatal prognosisof the disease, prompt and immediate therapeutic intervention isvery important. Although there is no standardized treatment, commonlyapplied glucocorticoids (GCS, and cyclosporine A (CsA areused. The study was aimed to a general characteristics of pathogenicfactors, clinical picture, laboratory features and results oftreatment in 8 children with RHPS /MAS. Material and methods: The study included 8 children (5 girls and3 boys aged 3 to 16 years (mean age was 10 years and 3 monthshospitalized in the Clinic of Pediatrics at IPCZD and in the Departmentof Pediatric Rheumatology at the Institute of Rheumatology in Warsaw. The analysis covered potential etiological factors, consideringthe basic disease, clinical symptoms (Table II, results oflaboratory tests (Table III, including immunological tests, appliedtherapy. In 4 patients, systemic-onset juvenile idiopathic arthritiswas accompanied by MAS, and in 2 patients it was the first manifestationof sJIA. In one patient, EBV infection was confirmed bythe polymerase chain reaction (case 1. In patient 3, PCR evaluationrevealed Cytomegalovirus (CMV infection. Cytomegalovirus infectionwas also confirmed in case 4

Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle.

Science.gov (United States)

Pasqualini, Claudia; Jorini, Mauro; Carloni, Ines; Giangiacomi, Mirella; Cetica, Valentina; Aricò, Maurizio; de Benedictis, Fernando Maria

2014-02-13

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.

The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation

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Israel Grilo

Full Text Available Background: The macro-aggregated albumin lung perfusion scan (99mTc-MAA is a diagnostic method for hepatopulmonary syndrome (HPS. Aim: To determine the sensitivity of 99mTc-MAA in diagnosing HPS, to establish the utility of 99mTc-MAA in determining the influence of HPS on hypoxemia in patients with concomitant pulmonary disease and to determine the correlation between 99mTc-MAA values and other respiratory parameters. Methods: Data from 115 cirrhotic patients who were eligible for liver transplantation (LT were prospectively analyzed. A transthoracic contrast echocardiography and 99mTc-MAA were performed in 85 patients, and 74 patients were diagnosed with HPS. Results: The overall sensitivity of 99mTc-MAA for the diagnosis of HPS was 18.9% (14/74 in all of the HPS cases and 66.7% (4/6 in the severe to very severe cases. In HPS patients who did not have lung disease, the degree of brain uptake of 99mTc-MAA was correlated with the alveolar-arterial oxygen gradient (A-a PO2 (r = 0.32, p < 0.05 and estimated oxygen shunt (r = 0.41, p < 0.05 and inversely correlated with partial pressure of arterial oxygen (PaO2 while breathing 100% O2 (r = -0.43, p < 0.05. The 99mTc-MAA was positive in 20.6% (7/36 of the patients with HPS and lung disease. The brain uptake of 99mTc-MAA was not associated with mortality and normalized in all cases six months after LT. Conclusions: The 99mTc-MAA is a low sensitivity test for the diagnosis of HPS that can be useful in patients who have concomitant lung disease and in severe to very severe cases of HPS. It was not related to mortality, and brain uptake normalized after LT.

A case of hemophagocytic lymphohistiocytosis presenting as pyrexia of unknown origin

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Indira Madhavan

2015-01-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a potentially fatal hyper inflammatory condition, which occurs as either primary (genetic or secondary (acquired due to impaired or absent function of natural killer cells and cytotoxic cells. Common secondary causes include viral and bacterial infections, autoimmune diseases, and hematological malignancies. Extensive phagocytosis of blood cells by histiocytes in bone marrow, spleen, liver and lymphnodes result in peripheral blood cytopenias, hepatosplenomegaly, and lymphadenopathy. We evaluated a case of pyrexia of unknown origin and found out that he fulfilled the criteria for diagnosing HLH. He was started on immunochemotherapy with etoposide, cyclosporine and steroids, but he succumbed to illness within 2 weeks of treatment. High index of suspicion is needed to diagnose HLH and prompt treatment on diagnosis can be lifesaving.

Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

OpenAIRE

Sonke, Gabe; Ludwig, Inge; Oosten, Hannah; Baars, Joke; Meijer, Ellen; Kater, Arnon; Jong, Daphne

2008-01-01

textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2 abnormal Epstein-Barr virus-associated diseases are seldom reported in individuals other than Japanese children and adolescents. We report a series of 2 adult non-Japanese patients with fatal chronic ac...

Complicated Crohn's-like colitis, associated with Hermansky-Pudlak syndrome, treated with Infliximab: a case report and brief review of the literature

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Kouklakis George

2007-12-01

Full Text Available Abstract Introduction Hermansky-Pudlak syndrome (HPS is a rare autosomal recessive inherited disorder consisting of a triad of albinism, increased bleeding tendency secondary to platelet dysfunction, and systemic complications associated with ceroid depositions within the reticuloendothelial system. HPS has been associated with gastrointestinal (GI complications related to chronic granulomatous colitis with pathologic features suggestive of Crohn's disease. This colitis can be severe and has been reported to be poorly responsive to medical therapies including antibiotics, corticosteroids, sulfasalazine, mesalamine and azathioprine. Case presentation We report a patient with HPS which was complicated by inflammatory bowel disease with clinical and pathologic features of Crohn's disease, refractory to antibiotics, corticosteroids and azathioprine. A trial of infliximab was attempted and repeated infusions produced a complete response. Conclusion The occurrence of ileitis and perianal lesions and also the histopathological findings in our case suggest that HPS and Crohn's disease may truly be associated. Given this similarity and the failure of the standard medical therapy of corticosteroids and azathioprine, our patient received infliximab with marked clinical improvement.

Techniques and training with GreenLight HPS120-W laser therapy of the prostate: Position paper

NARCIS (Netherlands)

Muir, Gordon; Gomez Sancha, Fernando; Bachmann, Alexander; Choi, Benjamin; Collins, Edward; de la Rosette, Jean; Reich, Oliver; Tabatabaei, Shahin; Woo, Henry

2008-01-01

We report the technical recommendations of the International GreenLight User Group on photoselective vaporization of the prostate in men with benign prostatic hyperplasia using the GreenLight HPS system (American Medical Systems, Minnetonka, Minnesota, USA). This high-power system employs a 120-W

CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

Science.gov (United States)

2017-07-13

Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

Improved severe hepatopulmonary syndrome after liver transplantation in an adolescent with end-stage liver disease secondary to biliary atresia

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Tae Jun Park

2014-03-01

Full Text Available Hepatopulmonary syndrome (HPS is a serious complication of end-stage liver disease, which is characterized by hypoxia, intrapulmonary vascular dilatation, and liver cirrhosis. Liver transplantation (LT is the only curative treatment modality for patients with HPS. However, morbidity and mortality after LT, especially in cases of severe HPS, remain high. This case report describes a patient with typical findings of an extracardiac pulmonary arteriovenous shunt on contrast-enhanced transesophageal echocardiography (TEE, and clubbing fingers, who had complete correction of HPS by deceased donor LT. The patient was a 16-year-old female who was born with biliary atresia and underwent porto-enterostomy on the 55th day after birth. She had been suffered from progressive liver failure with dyspnea, clubbing fingers, and cyanosis. Preoperative arterial blood gas analysis revealed severe hypoxia (arterial O2 tension of 54.5 mmHg and O2 saturation of 84.2%. Contrast-enhanced TEE revealed an extracardiac right-to-left shunt, which suggested an intrapulmonary arteriovenous shunt. The patient recovered successfully after LT, not only with respect to physical parameters but also for pychosocial activity, including school performance, during the 30-month follow-up period.

BMT Abatacept for Non-Malignant Diseases

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2018-05-16

Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

Cohort study comparing prostate photovaporisation with XPS 180W and HPS 120W laser.

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López, B; Capitán, C; Hernández, V; de la Peña, E; Jiménez-Valladolid, I; Guijarro, A; Pérez-Fernández, E; Llorente, C

2016-01-01

Prostate photovaporisation with Greenlight laser for the surgical treatment of benign prostate hyperplasia has rapidly evolve to the new XPS 180W. We have previously demonstrated the safety and efficacy of the HPS 120W. The aim of this study was to assess the functional and safety results, with a year of follow-up, of photovaporisation using the XPS 180W laser compared with its predecessor. A cohort study was conducted with a series of 191 consecutive patients who underwent photovaporisation between 1/2008 and 5/2013. The inclusion criteria were an international prostate symptom score (IPSS) >15 after medical failure, a prostate volume <80 cm(3) and a maximum flow <15 mL/s. We assessed preoperative and intraoperative variables (energy used, laser time and total surgical time), complications, catheter hours, length of stay and functional results (maximum flow, IPSS, prostate-specific antigen and prostate volume) at 3, 6 and 12 months. We analysed the homogeneity in preoperative characteristics of the 2 groups through univariate analysis techniques. The postoperative functional results were assessed through an analysis of variance of repeated measures with mixed models. A total of 109 (57.1%) procedures were performed using HPS 120W, and 82 (42.9%) were performed using XPS. There were no differences between the preoperative characteristics. We observed significant differences both in the surgical time and effective laser time in favour of the XPS system. This advantage was 11% (48 ± 15.7 vs. 53.8 ± 16.2, p<.05) and 9% (32.8 ± 11.7 vs. 36 ± 11.6, p<.05), respectively. There were no statistically significant differences in the rest of the analysed parameters. The technical improvements in the XPS 180W system help reduce surgical time, maintaining the safety and efficacy profile offered by the HPS 120W system, with completely superimposable results at 1 year of follow-up. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Capillary leak syndrome: etiologies, pathophysiology, and management.

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Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai

2017-07-01

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.

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Luisa Lorenzi

Full Text Available Hermansky Pudlak type 2 syndrome (HPS2 is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene. The defect results in the impairment of the adaptor protein 3 (AP-3 complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(brightCD16(- Natural Killer (NK cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

Science.gov (United States)

2018-04-19

Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy

Hemophagocytic lymphohistiocytosis preceded by Kikuchi disease in children

International Nuclear Information System (INIS)

Lim, Gye-Yeon; Cho, Bin; Chung, Nak Gyun

2008-01-01

Kikuchi disease (KD) is a type of benign, self-limiting lymphadenitis, but it has also been associated with hemophagocytic lymphohistiocytosis (HLH). To date, only a few reports have suggested an association between HLH and KD. To report the imaging findings and clinical characteristics of KD accompanied by HLH in children. Five children with a prolonged fever and cervical lymphadenopathy were diagnosed as having HLH accompanied by KD. The authors retrospectively analyzed the clinical characteristics and the imaging findings in these children. The histology of excision biopsy samples of cervical lymph nodes in all children confirmed the diagnosis of KD. HLH was confirmed by bone marrow biopsy and laboratory criteria provided by the Histiocyte Society. The greatest dimension of the enlarged nodes ranged from 0.5 cm to 2.5 cm and the nodes were most frequently located at level V. CT scans visualized perinodal infiltrates in most of the affected cervical nodes (four of five children) and extracervical nodes (three of three children). On enhanced CT scans, nonenhancing necrosis within the affected cervical nodes was noted in three children. KD might be related to HLH in children. Systemic evaluations and follow-up of children with KD might help to identify HLH related to KD. (orig.)

Hantavirus Pulmonary Syndrome

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... Infectious Diseases Division of High-Consequence Pathogens and Pathology How is HPS diagnosed? Diagnosing HPS in an individual who has only been infected for a few days is difficult, because early symptoms such as fever, muscle aches, and fatigue are easily confused with influenza. ...

Investigating the potential role of genetic and epigenetic variation of DNA methyltransferase genes in hyperplastic polyposis syndrome.

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Musa Drini

2011-02-01

Full Text Available Hyperplastic Polyposis Syndrome (HPS is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC. At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP, potentially linked to aberrant DNA methyltransferase (DNMT activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT, and negative regulators of Wnt signaling (such as WIF1. In this study, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, in the aetiology of HPS.We utilized high resolution melting (HRM analysis to screen 45 cases with HPS for novel sequence variants in DNMT1, DNMT3A, DNMT3B, and DNMT3L. 21 polyps from 13 patients were screened for BRAF and KRAS mutations, with assessment of promoter methylation in the DNMT1, DNMT3A, DNMT3B, DNMT3L MLH1, MGMT, and WIF1 gene promoters.No pathologic germline mutations were observed in any DNA-methyltransferase gene. However, the T allele of rs62106244 (intron 10 of DNMT1 gene was over-represented in cases with HPS (p<0.01 compared with population controls. The DNMT1, DNMT3A and DNMT3B promoters were unmethylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells with methylation level negatively correlated to expression level in normal colonic tissue. DNMT3L promoter hypomethylation was more often found in polyps harbouring KRAS mutations (p = 0.0053. BRAF mutations were common (11 out of 21 polyps, whilst KRAS mutations were identified in 4 of 21 polyps.Genetic or epigenetic alterations in DNMT genes do not appear to be associated with HPS, but further investigation of genetic variation at rs62106244 is justified given the high frequency of the minor allele in this case series.

Hamartomatous polyps - a clinical and molecular genetic study

DEFF Research Database (Denmark)

Jelsig, Anne Marie

2016-01-01

the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps...... appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand...

Transanal anopexy with HemorPex System (HPS) is effective in treating grade II and III hemorrhoids: medium-term follow-up.

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Basile, M; Di Resta, V; Ranieri, E

2016-06-01

Hemorrhoidal disease is a common proctologic disorder. The HemorPex System(®) (HPS) (Angiologica, S. Martino Siccomario PV, Italy) is an innovative surgical technique based on muco-hemorrhoidopexy without Doppler guidance. The aim of this study was to evaluate the efficacy of HPS in on the treatment of grade II and III hemorrhoids. One hundred patients with grade II and III hemorrhoidal disease were included in the study and operated on using HPS without Doppler guidance. The procedure consists of a mucopexy carried out by means of a dedicated rotating anoscope in the 6 relatively constant positions of the terminal branches of the superior hemorrhoidal artery. A direct follow-up was carried out on 100 patients for up to 3 months. A late analysis (>12 months postoperatively) was conducted by telephone interview. At follow-up the following parameters were considered: pain, bleeding, prolapse, difficulties with hygiene and patient satisfaction with treatment. Operative time was 16 ± 5 min. Three-month follow-up showed significant improvement of symptoms: pain was present in 10 (10 %) patients versus 45 (45 %) preoperatively; bleeding in 13 (13 %) of patients versus 57 (57 %) preoperatively; prolapse in 13 (13 %) of patients versus 45 (45 %) preoperatively and difficulties with hygiene in 1 (1 %) versus 24 (24 %) preoperatively (all p hemorrhoidal disease. Our results show that this simple technique may be an effective but due to the important limitations of this study (loss to follow-up, non-comparative study) further studies are required.

Preventing Hantavirus Pulmonary Syndrome (HPS)

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... Seoul Virus Infection Testing for Seoul Virus in Pet Rats: Information For Veterinarians Yosemite National Park Case Count Maps Epi ... or minimize contact with rodents in your home, workplace, or campsite. If rodents don’t find that ...

CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

International Nuclear Information System (INIS)

Chung, Tae Woong

2007-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT.

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Kobayashi, R; Tanaka, J; Hashino, S; Ota, S; Torimoto, Y; Kakinoki, Y; Yamamoto, S; Kurosawa, M; Hatakeyama, N; Haseyama, Y; Sakai, H; Sato, K; Fukuhara, T

2014-02-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P=0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

Wolman disease associated with hemophagocytic lymphohistiocytosis: attempts for an explanation.

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Taurisano, Roberta; Maiorana, Arianna; De Benedetti, Fabrizio; Dionisi-Vici, Carlo; Boldrini, Renata; Deodato, Federica

2014-10-01

The lysosomal acid lipase (LAL) is the enzyme responsible of the hydrolysis of cholesteryl esters and triglycerides within endo-lysosomes. Loss of enzyme activity leads to accumulation of cholesteryl esters and triglycerides in the lysosome of most tissues. The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition which may be genetically determined or secondary to infections, malignancies, immune deficiencies, and rheumatologic disorders. So far, some inborn errors of metabolism have been associated with HLH (e.g., lysinuric protein intolerance, Gaucher's disease), and it has been anecdotally described in three WD patients, without any specific pathogenetic hypothesis. Here, we report on a WD patient, showing clear clinical, biochemical, and histological features indicative of HLH. We discuss the pathophysiological role of cholesteryl ester-induced inflammasome activation in macrophages, leading to a secondary HLH. This case indicates that WD can cause secondary HLH and suggests that a careful metabolic workup should be performed when facing to a pediatric patient with HLH.

Diagnostic Challenge of Hepatopulmonary Syndrome in a Patient with Coexisting Structural Heart Disease

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Jorge M. Hurtado-Cordovi

2011-01-01

Full Text Available Hepatopulmonary syndrome (HPS is a severe complication seen in advance liver disease. Its prevalence among cirrhotic patients varies from 4–47 percent. HPS exact pathogenesis remains unknown. Patient presents with signs/symptoms of chronic liver disease, and dypsnea of variable severity. Our patient is a 62 years old white male with a known history of chronic hepatitis C, cirrhosis, ascites, and hypothyroidism who presented to GI/liver clinic complaining of 1 episode BRBPR, and exacerbating dypsnea associated with nausea and few episodes of non-bloody vomit. Physical exam showed, icterus, jaundice, few small spider angiomas on the chest, decrease breath sounds bilateral right more than left, and mild tachycardic. Abdominal exam revealed mid-line scar, moderated size ventral hernia, distention, diffused tenderness, and dullness to percussion. Laboratory result: CBC 5.2/13.2/37.6/83, LFTs 83/217/125/5.2/4.7/7.4, Pt 22.6 INR 1.9 PTT35.4. CT scan showed liver cirrhosis, abdominal varices, and moderated ascites collection around ventral hernia. Calculated A-a gradient was 49.5. Echocardiography revealed patent foramen ovale (PFO with predominant left to right shunt. In our case, existence of paten foramen ovale (PFO and atelectasis precludes definitive diagnosis of HPS. Presence of cardiopulmonary shunt could be partially responsible for the patient’s dypsnea exacerbation.

Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

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Kozo Nagai

Full Text Available BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2 and UNC13D mutation was in 10 (FHL3. In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5. Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s responsible for FHL remain to be identified.

Novel camelid antibody fragments targeting recombinant nucleoprotein of Araucaria hantavirus: a prototype for an early diagnosis of Hantavirus Pulmonary Syndrome.

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Soraya S Pereira

Full Text Available In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ₈₅ of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ₈₅. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB, surface plasmon resonance (SPR device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ₈₅ in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with

Association of Monoclonal Expansion of Epstein-Barr Virus-Negative CD158a+ NK Cells Secreting Large Amounts of Gamma Interferon with Hemophagocytic Lymphohistiocytosis▿

Science.gov (United States)

López-Álvarez, María R.; Martínez-Sánchez, María V.; Salgado-Cecilia, María G.; Campillo, José A.; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L.; Bas, Águeda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M.; Álvarez-López, María R.; Minguela, Alfredo

2009-01-01

We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

Primary Epstein-Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis.

Science.gov (United States)

Karrasch, Matthias; Felber, Jörg; Keller, Peter M; Kletta, Christine; Egerer, Renate; Bohnert, Jürgen; Hermann, Beate; Pfister, Wolfgang; Theis, Bernhard; Petersen, Iver; Stallmach, Andreas; Baier, Michael

2014-11-01

A case of primary Epstein-Barr virus (EBV) infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH) is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK) cell function, and a lack of hemophagocytosis.

Primary Epstein–Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis

OpenAIRE

Karrasch, Matthias; Felber, Jörg; Keller, Peter M.; Kletta, Christine; Egerer, Renate; Bohnert, Jürgen; Hermann, Beate; Pfister, Wolfgang; Theis, Bernhard; Petersen, Iver; Stallmach, Andreas; Baier, Michael

2014-01-01

A case of primary Epstein–Barr virus (EBV) infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH) is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK) cell function, and a lack of hemophagocytosis.

Primary Epstein–Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis

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Matthias Karrasch

2014-11-01

Full Text Available A case of primary Epstein–Barr virus (EBV infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK cell function, and a lack of hemophagocytosis.

Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

Science.gov (United States)

Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

2016-07-01

A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.

PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

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Patiroglu, T; Akar, H H; Unal, E; Chiang, S C; Schlums, H; Tesi, B; Ozkars, M Y; Karakukcu, M

2016-01-01

Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

Dengue fever as a cause of hemophagocytic lymphohistiocytosis.

Science.gov (United States)

Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, Débora Morais; Hirose, Maki; Ferronato, Angela Espósito; Pastorino, Antônio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias

2015-01-01

Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, providing suitable conditions for Aedes aegypti breeding and survival. In Brazil for instance it is from January to June. Dengue may cause marked changes in bone marrow that result in hypocellularity and, consequently, thrombocytopenia and leucopenia, along with an increase in hematocrit, which is secondary to capillary leakage. However, those abnormalities are usually self-limited, and do not warrant further investigations, such as a marrow biopsy or a myelogram. The occurrence of persistent reactive hemophagocytosis is uncommon and usually leads to serious adverse outcomes. The authors report the case of an 8-year old girl complaining of high-grade fever, malaise, headache, abdominal pain and a cutaneous rash. Laboratory examination revealed atypical lymphocytosis on peripheral blood count, hyperbilirrunemia, abnormal liver enzymes and clotting tests. Serology was positive for dengue. Because of the persistence of fever and laboratory examinations were consistent with hemophagocytic lymphohistiocytosis (HLH) a bone marrow aspiration was performed, which confirmed the presence of hemophagocytosis. Hence we report a rare presentation of dengue accompanied by self-limited HLH that hopefully evolve to favorable outcome.

Partial Oculocutaneous Albinism: Two Siblings with Features of both Hermansky Pudlak and Waardenburg's Syndrome.

Science.gov (United States)

Ishaq, Mazhar; Niazi, Muhammad Khizar; Khan, Muhammad Saim; Nadeem, Yasser

2015-04-01

Albinism is an inherited abnormality of melanin synthesis with incidence of one per 20,000 births. Its clinical manifestations are related to the reduction or absence of pigmentation in the visual system and/or the skin and teguments. The clinical spectrum of Oculocutaneous Albinism (OCA) has four types ranging from OCA 1 - 4, of which OCA 1, A-1 is the most severe form. Partial cutaneous albinism which is a subtype of OCA is associated with systemic immunodeficiency disorders like Chediak Higashi (CHS), Griscelli (GS) and Hermansky-Pudlak (HPS) syndromes. A7 years boy was labeled initially as a case of Hermansky Pudlak syndrome at the age of 01 year. He as well as his 4 years old younger brother when examined in detail along with audiological investigations were diagnosed as a rare presentation of both Hermansky Pudlak and Waardenburg's syndrome.

Assessment of the LV-C2 Stack Sampling Probe Location for Compliance with ANSI/HPS N13.1-1999

Energy Technology Data Exchange (ETDEWEB)

Glissmeyer, John A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Antonio, Ernest J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Flaherty, Julia E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2015-09-01

This document reports on a series of tests conducted to assess the proposed air sampling location for the Hanford Tank Waste Treatment and Immobilization Plant (WTP) Low-Activity Waste (LAW) C2V (LV-C2) exhaust stack with respect to the applicable criteria regarding the placement of an air sampling probe. Federal regulations require that a sampling probe be located in the exhaust stack according to the criteria established by the American National Standards Institute/Health Physics Society (ANSI/HPS) N13.1-1999, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stack and Ducts of Nuclear Facilities. These criteria address the capability of the sampling probe to extract a sample that represents the effluent stream. The tests were conducted on the LV-C2 scale model system. Based on the scale model tests, the location proposed for the air sampling probe in the scale model stack meets the requirements of the ANSI/HPS N13.1-1999 standard for velocity uniformity, flow angle, gas tracer and particle tracer uniformity. Additional velocity uniformity and flow angle tests on the actual stack will be necessary during cold startup to confirm the validity of the scale model results in representing the actual stack.

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.

Science.gov (United States)

Virdis, Francesco; Tacci, Sara; Messina, Federico; Varcada, Massimo

2013-11-27

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Passive Flora? Reconsidering Nature’s Agency through Human-Plant Studies (HPS

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John Charles Ryan

2012-08-01

Full Text Available Plants have been—and, for reasons of human sustenance and creative inspiration, will continue to be—centrally important to societies globally. Yet, plants—including herbs, shrubs, and trees—are commonly characterized in Western thought as passive, sessile, and silent automatons lacking a brain, as accessories or backdrops to human affairs. Paradoxically, the qualities considered absent in plants are those employed by biologists to argue for intelligence in animals. Yet an emerging body of research in the sciences and humanities challenges animal-centred biases in determining consciousness, intelligence, volition, and complex communication capacities amongst living beings. In light of recent theoretical developments in our understandings of plants, this article proposes an interdisciplinary framework for researching flora: human-plant studies (HPS. Building upon the conceptual formations of the humanities, social sciences, and plant sciences as advanced by Val Plumwood, Deborah Bird Rose, Libby Robin, and most importantly Matthew Hall and Anthony Trewavas, as well as precedents in the emerging areas of human-animal studies (HAS, I will sketch the conceptual basis for the further consideration and exploration of this interdisciplinary framework.

In vitro and in vivo activity of ribavirin against Andes virus infection.

Directory of Open Access Journals (Sweden)

David Safronetz

Full Text Available Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS. The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV, an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1. In hamsters, treatment with as little as 5 mg kg(-1 day(-1 was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1 day(-1. Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against

Diagnosing XLP1 in patients with hemophagocytic lymphohistiocytosis.

Science.gov (United States)

Meazza, Raffaella; Tuberosa, Claudia; Cetica, Valentina; Falco, Michela; Parolini, Silvia; Grieve, Sam; Griffiths, Gillian M; Sieni, Elena; Marcenaro, Stefania; Micalizzi, Concetta; Montin, Davide; Fagioli, Franca; Moretta, Alessandro; Mingari, Maria C; Moretta, Lorenzo; Notarangelo, Luigi D; Bottino, Cristina; Aricò, Maurizio; Pende, Daniela

2014-12-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, heterogeneous, hyperinflammmatory disorder. Prompt identification of inherited forms resulting from mutation in genes involved in cellular cytotoxicity can be crucial. X-linked lymphoproliferative disease 1 (XLP1), due to mutations in SH2D1A (Xq25) encoding signaling lymphocyte activation molecule-associated protein (SAP), may present with HLH. Defective SAP induces paradoxical inhibitory function of the 2B4 coreceptor and impaired natural killer (NK) (and T) cell response against EBV-infected cells. To characterize a cohort of patients with HLH and XLP1 for SAP expression and 2B4 function in lymphocytes, proposing a rapid diagnostic screening to direct mutation analysis. We set up rapid assays for 2B4 function (degranulation or (51)Cr-release) to be combined with intracellular SAP expression in peripheral blood NK cells. We studied 12 patients with confirmed mutation in SH2D1A and some family members. The combined phenotypic/functional assays allowed efficient and complete diagnostic evaluation of all patients with XLP1, thus directing mutation analysis and treatment. Nine cases were SAP(-), 2 expressed SAP with mean relative fluorescence intensity values below the range of healthy controls (SAP(dull)), and 1, carrying the R55L mutation, was SAP(+). NK cells from all patients showed inhibitory 2B4 function and defective killing of B-EBV cells. Carriers with SH2D1A mutations abolishing SAP expression and low percentage of SAP(+) cells showed neutral 2B4 function at the polyclonal NK cell level. Three novel SH2D1A mutations have been identified. Study of SAP expression is specific but may have insufficient sensitivity for screening XLP1 as a single tool. Combination with 2B4 functional assay allows identification of all cases. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Ab initio structural and spectroscopic study of HPS{sup x} and HSP{sup x} (x = 0,+1,−1) in the gas phase

Energy Technology Data Exchange (ETDEWEB)

Yaghlane, Saida Ben [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications – LSAMA, Université de Tunis, Tunis (Tunisia); Cotton, C. Eric; Francisco, Joseph S., E-mail: francisc@purdue.edu, E-mail: hochlaf@univ-mlv.fr [Department of Chemistry and Department of Earth and Atmospheric Science, Purdue University, West Lafayette, Indiana 49707 (United States); Linguerri, Roberto; Hochlaf, Majdi, E-mail: francisc@purdue.edu, E-mail: hochlaf@univ-mlv.fr [Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, Université Paris-Est, 5 bd Descartes, 77454 Marne-la-Vallée (France)

2013-11-07

Accurate ab initio computations of structural and spectroscopic parameters for the HPS/HSP molecules and corresponding cations and anions have been performed. For the electronic structure computations, standard and explicitly correlated coupled cluster techniques in conjunction with large basis sets have been adopted. In particular, we present equilibrium geometries, rotational constants, harmonic vibrational frequencies, adiabatic ionization energies, electron affinities, and, for the neutral species, singlet-triplet relative energies. Besides, the full-dimensional potential energy surfaces (PESs) for HPS{sup x} and HSP{sup x} (x = −1,0,1) systems have been generated at the standard coupled cluster level with a basis set of augmented quintuple-zeta quality. By applying perturbation theory to the calculated PESs, an extended set of spectroscopic constants, including τ, first-order centrifugal distortion and anharmonic vibrational constants has been obtained. In addition, the potentials have been used in a variational approach to deduce the whole pattern of vibrational levels up to 4000 cm{sup −1} above the minima of the corresponding PESs.

Assessment of the Idaho National Laboratory Hot Fuel Examination Facility Stack Monitoring Site for Compliance with ANSI/HPS N13.1 1999

International Nuclear Information System (INIS)

Glissmeyer, John A.; Flaherty, Julia E.

2010-01-01

This document reports on a series of tests to determine whether the location of the air sampling probe in the Hot Fuels Examination Facility (HFEF) heating, ventilation and air conditioning (HVAC) exhaust duct meets the applicable regulatory criteria regarding the placement of an air sampling probe. Federal regulations require that a sampling probe be located in the exhaust stack according to the criteria of the ANSI/HPS N13.1-1999, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stacks and Ducts of Nuclear Facilities. These criteria address the capability of the sampling probe to extract a sample that is representative of the effluent stream. The tests conducted by PNNL during July 2010 on the HFEF system are described in this report. The sampling probe location is approximately 20 feet from the base of the stack. The stack base is in the second floor of the HFEF, and has a building ventilation stream (limited potential radioactive effluent) as well as a process stream (potential radioactive effluent, but HEPA-filtered) that feeds into it. The tests conducted on the duct indicate that the process stream is insufficiently mixed with the building ventilation stream. As a result, the air sampling probe location does not meet the criteria of the N13.1-1999 standard. The series of tests consists of various measurements taken over a grid of points in the duct cross section at the proposed sampling-probe location. The results of the test series on the HFEF exhaust duct as it relates to the criteria from ANSI/HPS N13.1-1999 are desribed in this report. Based on these tests, the location of the air sampling probe does not meet the requirements of the ANSI/HPS N13.1-1999 standard, and modifications must be made to either the HVAC system or the air sampling probe for compliance. The recommended approaches are discussed and vary from sampling probe modifications to modifying the junction of the two air exhaust streams.

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.

Stemcell Information: SKIP000382 [SKIP Stemcell Database[Archive

Lifescience Database Archive (English)

Full Text Available SKIP000382 ... Diseased HPS0244 HPS0244 ... X連鎖αサラセミア·精神遅滞（ATR-X）症候群 D560 X-Linked alpha-Thalassemia...fic iPS cell line derived from a patient : X-Linked alpha-Thalassemia, Mental Retardation Syndrome (ATR-X sy

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

Directory of Open Access Journals (Sweden)

Nicole Haese

Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral

Hydropericardium syndrome: current state and future developments.

Science.gov (United States)

Asthana, Manu; Chandra, Rajesh; Kumar, Rajesh

2013-05-01

Hydropericardium syndrome (HPS) is a highly infectious disease caused by fowl adenovirus serotype 4 (FAV-4) affecting poultry, especially broiler birds. The disease was initially reported from Angara Goth, Pakistan, and then from India during 1994, in the poultry belt of Jammu and Kashmir, and thereafter, from almost all parts of the country, causing heavy economic losses to the poultry industry. The disease occurs predominantly in broilers of the age group of 3-5 weeks, characterized by sudden onset of high mortality up to 80 %. The causative agent of HPS is fowl adenovirus 4, which is a member of the species Fowl Adenovirus C, genus Aviadenovirus, family Adenoviridae [60]. FAV-4 is non-enveloped and icosahedral in shape, measuring 70-90 nm in size and containing a linear dsDNA of approximately 45 kb in size as its genome. The livers of affected birds show necrotic foci and basophilic intranuclear inclusion bodies in the hepatocytes. The disease can be diagnosed from its gross and microscopic changes in the liver and by various serological tests, such as agar gel immunodiffusion, counterimmunoelectrophoresis, indirect haemagglutination, fluorescent antibody techniques, and ELISA. In the past few years, PCR has been used as a rapid diagnostic tool for the detection of fowl adenoviruses. The disease has been brought under control by the use of formalin-inactivated, attenuated or live vaccines in experimentally infected birds. Advancement in the field of computational immunology accelerates knowledge acquisition and simultaneously reduces the time and effort involved in screening potential epitopes, leading toward the development of epitope-based vaccines.

Stemcell Information: SKIP000388 [SKIP Stemcell Database[Archive

Lifescience Database Archive (English)

Full Text Available SKIP000388 ... Diseased HPS0207 HPS0207 ... X連鎖アルファ-サラセミア・精神遅滞(ATR-X)症候群 ... Alpha-Thalassemia...l line derived from a patient :Alpha-Thalassemia/Mental Retardation Syndrome, X-Linked; ATRX. ... 疾患特異的iPS細胞株。X

Knowledge and practices about hantavirus pulmonary syndrome in a cluster of Japanese communities in Argentina Conocimientos y prácticas relacionados con el síndrome pulmonar por hantavirus en un conglomerado de comunidades japonesas en Argentina

Directory of Open Access Journals (Sweden)

Kuniaki Suzuki

2009-02-01

Full Text Available OBJECTIVES: To provide information on hantavirus pulmonary syndrome (HPS knowledge and practices among a cluster of the rural Japanese communities near La Plata in central Ar gentina, an area with confirmed HPS cases. Particular emphasis was placed on testing the hy pothesis that there would be differences between household use of HPS prevention measures based on the head-of-household's knowledge of HPS. METHODS: A questionnaire was designed in three sections: (1 household demographic char acteristics, (2 HPS knowledge, and (3 HPS preventive measures. Questionnaires were given to the household head or other adult representing the household at an HPS prevention semi nar sponsored by the Japanese Association of La Plata in February 2007. Total HPS knowl edge scores were dichotomized into high (equal to or more than the median knowledge score and low (less than the median. Differences between the two household groups were catego rized, according to the degree of HPS knowledge, and analyzed. RESULTS: The 86 households that responded accounted for about 72% of the total study households in the area. The median knowledge score of 5 (range: 0-9, of 10 divided the study households into two groups: high knowledge score group (n = 40 and low knowledge score group (n = 46. The findings suggest an association between a household's accurate HPS knowledge and its respective use of HPS preventive measures. CONCLUSION: The findings of the study have important implications for taking further steps toward improved HPS management and prevention strategies.OBJETIVOS: Documentar los conocimientos y las prácticas relacionadas con el síndrome pulmonar por hantavirus (SPH en un conglomerado de comunidades rurales japonesas cerca de La Plata, en la parte central de Argentina, una zona con casos confirmados de SPH. Se hizo hincapié especial en probar la hipótesis de que habría diferencias en el empleo de medidas preventivas contra el SPH en los hogares según el

X-linked inhibitor of apoptosis (XIAP) deficiency

DEFF Research Database (Denmark)

Speckmann, C.; Lehmberg, K.; Albert, M.H.

2013-01-01

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant...

How People Get Hantavirus Pulmonary Syndrome (HPS)

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... Preventing Seoul Virus Infection in Pet Rats and People FAQs: Seoul Virus Cleaning Up After Pet Rodents to Reduce the Risk of Seoul Virus ... Bolivia, Brazil, Chile, Panama, Paraguay, and Uruguay. Can pets ... rodents into contact with people if they catch such animals and carry them ...

Reported Cases of HPS (Hantavirus Pulmonary Syndrome)

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... Brazil, Chile, Ecuador, Paraguay, Panama and Uruguay and Venezuela. Large outbreaks have been rare and have usually ... Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton ...

Hypoalbuminaemia is an independent predictor for hemophagocytic lymphohistiocytosis in childhood Epstein-Barr virus-associated infectious mononucleosis.

Science.gov (United States)

Huang, Shu-Ching; Chen, Jiann-Shiuh; Cheng, Chao-Neng; Yang, Yao-Jong

2012-11-01

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal condition in children with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). This study aimed to identify commonly available clinical and laboratory predictors that might help clinicians decide to perform the bone marrow and immunological tests for HLH in paediatric EBV-associated IM. A retrospective case-control study of patients aged 70% of patients) were fever, lymphadenopathy and hepatomegaly. In addition to the diagnostic criteria of HLH including fever, splenomegaly, cytopenia, hyperferritinaemia, hypertriglyceridemia and/or hypofibrinogenaemia, children with HLH had a significantly higher rate of prolonged fever >10 d, hepatomegaly, jaundice, general malaise, elevated aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and hypoalbuminaemia compared to those with IM (all P < 0.01). Multiple logistic regression confirmed that hypoalbuminaemia (OR = 23.1, P = 0.01) was an independent predictor of paediatric HLH, with a high sensitivity (96%) and a good negative likelihood ratio (0.06) in patients with EBV-associated IM. Hypoalbuminaemia is a unique characteristic and potentially a valuable predictor for HLH in paediatric EBV-associated IM. © 2012 John Wiley & Sons A/S.

The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.

Science.gov (United States)

Qian, Yaping; Johnson, Judith A; Connor, Jessica A; Valencia, C Alexander; Barasa, Nathaniel; Schubert, Jeffery; Husami, Ammar; Kissell, Diane; Zhang, Ge; Weirauch, Matthew T; Filipovich, Alexandra H; Zhang, Kejian

2014-06-01

The mutations in UNC13D are responsible for familial hemophagocytic lymphohistiocytosis (FHL) type 3. A 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in UNC13D were recently reported in European and Asian FHL3 patients. We sought to determine the prevalence of these three non-coding mutations in North American FHL patients and evaluate the significance of examining these new mutations in genetic testing. We performed DNA sequencing of UNC13D and targeted analysis of these three mutations in 1,709 North American patients with a suspected clinical diagnosis of hemophagocytic lymphohistiocytosis (HLH). The 253-kb inversion, intronic mutations c.118-308C > T and c.118-307G > A were found in 11, 15, and 4 patients, respectively, in which the genetic basis (bi-allelic mutations) explained 25 additional patients. Taken together with previously diagnosed FHL3 patients in our HLH patient registry, these three non-coding mutations were found in 31.6% (25/79) of the FHL3 patients. The 253-kb inversion, c.118-308C > T and c.118-307G > A accounted for 7.0%, 8.9%, and 1.3% of mutant alleles, respectively. Significantly, eight novel mutations in UNC13D are being reported in this study. To further evaluate the expression level of the newly reported intronic mutation c.118-307G > A, reverse transcription PCR and Western blot analysis revealed a significant reduction of both RNA and protein levels suggesting that the c.118-307G > A mutation affects transcription. These specified non-coding mutations were found in a significant number of North American patients and inclusion of them in mutation analysis will improve the molecular diagnosis of FHL3. © 2014 Wiley Periodicals, Inc.

A case report and clinical approach to silver blonde hair

African Journals Online (AJOL)

Sana Durrani

2015-09-29

Sep 29, 2015 ... Abstract Griscelli syndrome type 2 is a rare autosomal recessive disease caused by mutations in the. RAB27A gene. It is characterized by pigmentary dilution of the skin and hair causing silvery gray hair, hemophagocytic lymphohistiocytosis and characteristic light microscopy findings in scalp hair.

Efficacy of Prompt Initiation of Antiretroviral Therapy in the Treatment of Hemophagocytic Lymphohistiocytosis Triggered by Uncontrolled Human Immunodeficiency Virus

Directory of Open Access Journals (Sweden)

Bryan P. Fitzgerald

2017-01-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART was initiated with darunavir, ritonavir, tenofovir, and emtricitabine. Within one week of initiation of ART, the patient began to improve clinically and hematologically and was stable enough for discharge from the hospital three weeks after starting therapy. This case suggests that treatment with ART in patients with HIV-associated HLH should be considered even in critically ill patients with low CD4 counts.

Control and diagnostics of technical state of main electro technical and thermal equipment of NPP, TPS and HPS on the basis of thermovision technologies

International Nuclear Information System (INIS)

Banduryan, B.B.; Fedorenko, G.M.; Ostapchuk, L.B.; Saratov, V.O.

2006-01-01

The opportunity of using of thermovision technologies for detection of defects NPP, TPS and HPS electro technical and power equipment is shown. The results of thermovision monitoring of a turbine generator stator technical state are represented. The method for thermovision control of a technical state of a electrical machines and apparatus construction elements, for which the patent of Ukraine have been obtained, is described. he verification of the offered expedient thermovision control and diagnostics at 'Elektrovazhmash' factory was carried out

Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

Science.gov (United States)

Hutton, Saunie M; Spritz, Richard A

2008-10-01

Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by absent or reduced pigmentation of the skin, hair, and eyes. In humans, four genes have been associated with "classical" OCA and another 12 genes with syndromic forms of OCA. To assess the prevalence of different forms of OCA and different gene mutations among non-Hispanic Caucasian patients, we performed DNA sequence analysis of the four genes associated with "classical" OCA (TYR, OCA2, TYRP1, SLC45A2), the two principal genes associated with syndromic OCA (HPS1, HPS4), and a candidate OCA gene (SILV), in 121 unrelated, unselected non-Hispanic/Latino Caucasian patients carrying the clinical diagnosis of OCA. We identified apparent pathologic TYR gene mutations in 69% of patients, OCA2 mutations in 18%, SLC45A2 mutations in 6%, and no apparent pathological mutations in 7% of patients. We found no mutations of TYRP1, HPS1, HPS4, or SILV in any patients. Although we observed a diversity of mutations for each gene, a relatively small number of different mutant alleles account for a majority of the total. This study demonstrates that, contrary to long-held clinical lore, OCA1, not OCA2, is by far the most frequent cause of OCA among Caucasian patients.

Investigation of high pressure steaming (HPS) as a thermal treatment for lipid extraction from Chlorella vulgaris.

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Aguirre, Ana-Maria; Bassi, Amarjeet

2014-07-01

Biofuels from algae are considered a technically viable energy source that overcomes several of the problems present in previous generations of biofuels. In this research high pressure steaming (HPS) was studied as a hydrothermal pre-treatment for extraction of lipids from Chlorella vulgaris, and analysis by response surface methodology allowed finding operational points in terms of target temperature and algae concentration for high lipid and glucose yields. Within the range covered by these experiments the best conditions for high bio-crude yield are temperatures higher than 174°C and low biomass concentrations (<5 g/L). For high glucose yield there are two suitable operational ranges, either low temperatures (<105°C) and low biomass concentrations (<4 g/L); or low temperatures (<105°C) and high biomass concentrations (<110 g/L). High pressure steaming is a good hydrothermal treatment for lipid recovery and does not significantly change the fatty acids profile for the range of temperatures studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two Novel Mutations Identified in an African-American Child with Chediak-Higashi Syndrome

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Kerry Morrone

2010-01-01

Full Text Available Background. Chediak-Higashi syndrome (CHS is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an “accelerated phase” characterized by hemophagocytic lymphohistiocytosis (HLH. The disease is caused by mutations in the CHS1/LYST gene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in the CHS1 gene: c.3622C>T (p.Q1208X and c.11002G>T (p.E3668X. Conclusions. Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in the CHS1 gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS.

Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

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Ameli, Fereshteh; Ghafourian, Firouzeh; Masir, Noraidah

2014-08-27

Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

Signs and Symptoms for Hantavirus Pulmonary Syndrome (HPS)

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... hips, back, and sometimes shoulders. These symptoms are universal. There may also be headaches, dizziness, chills, and ... site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple ...

Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause.

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Jing-Shi, Wang; Yi-Ni, Wang; Lin, Wu; Zhao, Wang

2015-05-01

Our aim was to evaluate the clinical value of splenectomy as a treatment for relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause in adults. We retrospectively reviewed the clinical data from medical records of 19 adults with relapsed HLH of unknown cause treated with splenectomy in our institution from June 2007 to March 2014. To rule out possible underlying diseases, including infection, autoimmune disease, neoplasms, and primary HLH, the patients had undergone examinations including F18 fluoro-2-deoxyglucose positron emission tomography/computed tomography, HLH-associated gene defects, and lymph node biopsies. Twelve patients (63.2%) achieved partial responses (PR), whereas seven patients (36.8%) had no response (NR) prior to splenectomy. Infection and hemorrhage were the main complications of splenectomy. Eighteen cases were evaluable after follow-up. Seven cases with histopathologic diagnoses of lymphoma had received chemotherapy, four of whom had achieved complete responses (CR), one PR, and two NR. Maintenance treatment was ceased 2 or 3 months after splenectomy in the other 11 cases, five of whom had CR, four PR, and two NR. Eleven of 18 cases (61.1%) survived with a median follow-up of 25 months (range 3-79 months) for survivors. Twelve- and 36-month progression-free survival rates were 48 and 24%, respectively; 12- and 36-month overall survival rates were 57 and 25%, respectively. Median survival time was 22 months. Our results indicate splenectomy may be an effective means of diagnosis and treatment of relapsed HLH of unknown cause. Further study is required to establish the mechanism and value of splenectomy in this disease.

The Loss of Vacuolar Protein Sorting 11 (vps11) Causes Retinal Pathogenesis in a Vertebrate Model of Syndromic Albinism

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Thomas, Jennifer L.; Vihtelic, Thomas S.; denDekker, Aaron D.; Willer, Gregory; Luo, Xixia; Murphy, Taylor R.; Gregg, Ronald G.; Hyde, David R.

2011-01-01

Purpose. To establish the zebrafish platinum mutant as a model for studying vision defects caused by syndromic albinism diseases such as Chediak-Higashi syndrome, Griscelli syndrome, and Hermansky-Pudlak syndrome (HPS). Methods. Bulked segregant analysis and candidate gene sequencing revealed that the zebrafish platinum mutation is a single-nucleotide insertion in the vps11 (vacuolar protein sorting 11) gene. Expression of vps11 was determined by RT-PCR and in situ hybridization. Mutants were analyzed for pigmentation defects and retinal disease by histology, immunohistochemistry, and transmission electron microscopy. Results. Phenocopy and rescue experiments determined that a loss of Vps11 results in the platinum phenotype. Expression of vps11 appeared ubiquitous during zebrafish development, with stronger expression in the developing retina and retinal pigmented epithelium (RPE). Zebrafish platinum mutants exhibited reduced pigmentation in the body and RPE; however, melanophore development, migration, and dispersion occurred normally. RPE, photoreceptors, and inner retinal neurons formed normally in zebrafish platinum mutants. However, a gradual loss of RPE, an absence of mature melanosomes, and the subsequent degradation of RPE/photoreceptor interdigitation was observed. Conclusions. These data show that Vps11 is not necessary for normal retinal development or initiation of melanin biosynthesis, but is essential for melanosome maturation and healthy maintenance of the RPE and photoreceptors. PMID:21330665

MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular Endothelial Cells in Hepatopulmonary Syndrome

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Jing Zeng

2015-10-01

Full Text Available Background/Aims: Pulmonary microvascular endothelial cell (PMVEC proliferation and angiogenesis contribute to the development of hepatopulmonary syndrome (HPS. MicroRNA-199a-5p (miR-199a-5p has emerged as a potent regulator of angiogenesis, and its expression levels significantly decrease in the serum of patients with hepatopathy. However, it has not been reported about whether miR-199a-5p might control PMVEC proliferation. Here, we described the miR-199a-5p governing PMVEC proliferation in HPS. Methods: PMVECs were treated with rat serum from common bile duct ligation (CBDL or sham. MiR-199a-5p mimic or inhibitor was used to change the miR-199a-5p expression. Knockdown of caveolin-1 (Cav-1 was performed using siRNA. NSC-23766 was used to inhibit Rac1 activity. Gene and protein expressions were quantified by qRT-PCR and western blot. Cell proliferation was analyzed by 3H-TdR incorporation and CCK-8 assays. Stress fibers were detected by immunofluorescence. Results: CBDL rat serum induced the down-regulation of miR-199a-5p. Delivery of miR-199a-5p suppressed the CBDL rat serum-induced PMVEC proliferation whereas knockdown of miR-199a-5p promoted PMVEC proliferation. This was accompanied by a decrease and an increase in Cav-1 expression, respectively. Cav-1 siRNA abolished the enhancement of PMVEC proliferation induced by the miR-199a-5p inhibition. Although stress fibers were disrupted in Cav-1 deficient cells, NSC-23766 increased stress fibers and contributed to cell proliferation. Conclusions: CBDL rat serum induced down-regulation of miR-199a-5p in PMVECs, which led to an increase of Cav-1 gene expression. Increased Cav-1 expression, by inhibiting Rac1 activity, led to the formation of stress fibers, which contribute to PMVEC proliferation and thus the pathogenesis of HPS.

An Unusual Case of Refractory Hypoxia on the ICU

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Phillips, Caroline; Harris, Clare; Pulimood, Thomas; Ring, Liam

2018-01-01

We present the case of a 68-year-old gentleman who presented with breathlessness and was found to have NSTEMI, pulmonary oedema, and hypoxia. He remained hypoxic despite appropriate treatment and was found to have preserved LV function and raised cardiac output. CT pulmonary angiogram was negative but a cirrhotic liver was incidentally noted and later confirmed via ultrasound. Bedside examination was positive for orthodeoxia, suggesting a diagnosis of hepatopulmonary syndrome (HPS). The finding of significant intrapulmonary shunting on “bubble” echocardiography confirmed the diagnosis. This patient did not have previously diagnosed liver disease and had largely normal LFTs when the diagnosis was first suspected. We discuss HPS in the context of ICU and suggest how it may be screened for using simple tests. There is no correlation between the presence of HPS and severity of liver disease, yet we believe this is the first reported adult case of HPS on the ICU without previously diagnosed cirrhosis. PMID:29850271

Characterization of Epstein-Barr virus (EBV) BZLF1 gene promoter variants and comparison of cellular gene expression profiles in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis.

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Imajoh, Masayuki; Hashida, Yumiko; Murakami, Masanao; Maeda, Akihiko; Sato, Tetsuya; Fujieda, Mikiya; Wakiguchi, Hiroshi; Daibata, Masanori

2012-06-01

Epstein-Barr virus (EBV) genotypes can be distinguished based on gene sequence differences in EBV nuclear antigens 2, 3A, 3B, and 3C, and the BZLF1 promoter zone (Zp). EBV subtypes and BZLF1 Zp variants were examined in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis. The results of EBV typing showed that samples of infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis all belonged to EBV type 1. However, sequencing analysis of BZLF1 Zp found three polymorphic Zp variants in the same samples. The Zp-P prototype and the Zp-V3 variant were both detected in infectious mononucleosis and chronic active EBV infection. Furthermore, a novel variant previously identified in Chinese children with infectious mononucleosis, Zp-V1, was also found in 3 of 18 samples of infectious mononucleosis, where it coexisted with the Zp-P prototype. This is the first evidence that the EBV variant distribution in Japanese patients resembles that found in other Asian patients. The expression levels of 29 chronic active EBV infection-associated cellular genes were also compared in the three EBV-related disorders, using quantitative real-time reverse transcription polymerase chain reaction analysis. Two upregulated genes, RIPK2 and CDH9, were identified as common specific markers for chronic active EBV infection in both in vitro and in vivo studies. RIPK2 activates apoptosis and autophagy, and could be responsible for the pathogenesis of chronic active EBV infection. Copyright © 2012 Wiley Periodicals, Inc.

Disruption of AP3B1 by a chromosome 5 inversion: a new disease mechanism in Hermansky-Pudlak syndrome type 2.

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Jones, Matthew L; Murden, Sherina L; Brooks, Claire; Maloney, Viv; Manning, Richard A; Gilmour, Kimberly C; Bharadwaj, Vandana; de la Fuente, Josu; Chakravorty, Subarna; Mumford, Andrew D

2013-04-04

Hermansky-Pudlak syndrome 2 (HPS2; OMIM #608233) is a rare, autosomal recessive disorder caused by loss-of-function genetic variations affecting AP3B1, which encodes the β3A subunit of the adaptor-related protein complex 3 (AP3). Phenotypic characteristics include reduced pigmentation, absent platelet dense granule secretion, neutropenia and reduced cytotoxic T lymphocyte (CTL) and natural killer (NK) cell function. To date HPS2 has been associated with non-synonymous, stop-gain or deletion-insertion nucleotide variations within the coding region of AP3B1. We describe a consanguineous female infant with reduced pigmentation, neutropenia and recurrent infections. Platelets displayed reduced aggregation and absent ATP secretion in response to collagen and ADP, indicating a platelet dense granule defect. There was increased basal surface expression of CD107a (lysosome-associated membrane protein 1(LAMP-1)) on NK cells and CTLs from the study subject and a smaller increase in the percentage of CD107a positive cells after stimulation compared to most healthy controls. Immunoblotting of protein extracts from EBV-transformed lymphoblasts from the index case showed absent expression of full-length AP-3 β3A subunit protein, confirming a phenotypic diagnosis of HPS2.The index case displayed a homozygous pericentric inv(5)(p15.1q14.1), which was also detected as a heterozygous defect in both parents of the index case. No loss of genetic material was demonstrated by microarray comparative genome hybridisation at 60kb resolution. Fluorescence in-situ hybridisation using the 189.6kb probe RP11-422I12, which maps to 5q14.1, demonstrated dual hybridisation to both 5q14.1 and 5p15.1 regions of the inverted Chr5. The RP11-422I12 probe maps from intron 1 to intron 16 of AP3B1, thus localising the 5q inversion breakpoint to within AP3B1. The probe RP11-211K15, which corresponds to an intergenic region on 5p also showed dual hybridisation, enabling localisation of the 5p inversion

to generation

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Michał Otręba

2014-09-01

Full Text Available Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. This article presents selected hypopigmentary disorders, which can be divided into hypomelanocytoses and hypomelanoses. Hereditary hypomelanoses are caused by abnormal melanin biosynthesis as well as by abnormal transfer of mature melanosomes to melanocyte dendrites and to neighboring cells. These disorders are represented by oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Menkes syndrome and phenylketonuria, and are caused by different mutations of the following genes: TYR, P, TRP1, MATP, HPS, CHS, MYO5A, RAB27A, MLPH, ATP7A and PAH. Oculocutaneous albinism is caused by a deficiency of melanin pigment in the skin, hair, and eye and results from mutations in the TYR, P, TRP1 and MATP genes involved in the biosynthesis of melanin pigment. Mutations in the HPS, CHS, MYO5A, RAB27A and MLPH genes, which regulate the biogenesis, maturation and transfer of me-lanosomes to neighboring cells, are responsible for such disorders as Hermansky-Pudlak, Chediak-Higashi and Griscelli syndromes. In turn, mutations of the ATP7A and PAH genes, regulating intracellular copper concentration and activity of phenylalanine hydroxylase, lead to Menkes syndrome and phenylketonuria.

Landscape, Environmental and Social Predictors of Hantavirus Risk in São Paulo, Brazil.

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Paula Ribeiro Prist

Full Text Available Hantavirus Pulmonary Syndrome (HPS is a disease caused by Hantavirus, which are negative-sense RNA viruses in the family Bunyaviridae that are highly virulent to humans. Numerous factors modify risk of Hantavirus transmission and consequent HPS risk. Human-driven landscape change can foster transmission risk by increasing numbers of habitat generalist rodent species that serve as the principal reservoir host. Climate can also affect rodent population dynamics and Hantavirus survival, and a number of social factors can influence probability of HPS transmission to humans. Evaluating contributions of these factors to HPS risk may enable predictions of future outbreaks, and is critical to development of effective public health strategies. Here we rely on a Bayesian model to quantify associations between annual HPS incidence across the state of São Paulo, Brazil (1993-2012 and climate variables (annual precipitation, annual mean temperature, landscape structure metrics (proportion of native habitat cover, number of forest fragments, proportion of area planted with sugarcane, and social factors (number of men older than 14 years and Human Development Index. We built separate models for the main two biomes of the state (cerrado and Atlantic forest. In both biomes Hantavirus risk increased with proportion of land cultivated for sugarcane and HDI, but proportion of forest cover, annual mean temperature, and population at risk also showed positive relationships in the Atlantic forest. Our analysis provides the first evidence that social, landscape, and climate factors are associated with HPS incidence in the Neotropics. Our risk map can be used to support the adoption of preventive measures and optimize the allocation of resources to avoid disease propagation, especially in municipalities that show medium to high HPS risk (> 5% of risk, and aimed at sugarcane workers, minimizing the risk of future HPS outbreaks.

Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

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Ellis, Esther M.; Pérez-Padilla, Janice; González, Liza; Poole-Smith, B. Katherine; Lebo, Emmaculate; Baker, Charlotte; Delorey, Mark J.; Torres-Velasquez, Brenda; Ochoa, Eduardo; Rivera-Garcia, Brenda; Díaz-Pinto, Hector; Clavell, Luis; Puig-Ramos, Anabel; Janka, Gritta E.; Tomashek, Kay M.

2016-01-01

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury. PMID:27556807

Immunologic difference between hypersensitivity to mosquito bite and hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection.

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Wen-I Lee

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB, a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV, may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients and 14 HMB episodes (4 patients, there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+ lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+ increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies.

Hereditary Hypokalemic salt-losing tubular disorders

International Nuclear Information System (INIS)

Peters, M.; Konard, M.; Seyberth, H.W.

2003-01-01

The inherited hypokalemic tubular disorders are frequently summarized under the heading Bartter Syndrome since they share several clinical and biochemical findings such as renal salt wasting, hypokalemic metabolic alkalosis, normal blood pressure despite hypereninemic hyperaldosteronism and hyperplasia of the juxtaglomerular apparatus. However, careful characterization of the clinical phenotype and correlation with the clinical phenotype and the correlation with the underlying molecular basis justifies the differentiation into at least four distinct disease entities: (i) the hyperprostaglandin E syndrome or antenatal variant of Bartter syndrome (HPS/aBS), which is caused by mutations in either the Na-K-2Cl cotransporter or the potassium channel of the medullary thick ascending limb of Henle's loop; (ii) the HPS/aBS with sensorineural deafness which results from inactivating mutation in the Barttin beta-subunit of the renal chloride channels; (iii) the classic Bartter syndrome caused by mutations in the chloride channel of the distal nephron; and (iv)Gitelman's variant of Bartter syndrome which is caused by mutations of the Na-Cl cotransporter of the distal convoluted tubule. This review will summarize the clinical characteristics of these diseases and progress recently made in the identification of the underlying molecular defects that will hopefully add to the current knowledge of the pathogenesis of these diseases. (author)

Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy.

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Messina, Chiara; Zecca, Marco; Fagioli, Franca; Rovelli, Attilio; Giardino, Stefano; Merli, Pietro; Porta, Fulvio; Aricò, Maurizio; Sieni, Elena; Basso, Giuseppe; Ripaldi, Mimmo; Favre, Claudio; Pillon, Marta; Marzollo, Antonio; Rabusin, Marco; Cesaro, Simone; Algeri, Mattia; Caniglia, Maurizio; Di Bartolomeo, Paolo; Ziino, Ottavio; Saglio, Francesco; Prete, Arcangelo; Locatelli, Franco

2018-06-01

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 + cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Structural and functional analysis of perforin mutations in association with clinical data of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) patients

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An, Omer; Gursoy, Attila; Gurgey, Aytemiz; Keskin, Ozlem

2013-01-01

Perforin plays a key role in the immune system via pore formation at the target cell membrane in the elimination of virus-infected and transformed cells. A vast number of observed mutations in perforin impair this mechanism resulting in a rare but fatal disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Here we report a comprehensive in silico structural analysis of a collection of 76 missense perforin mutations based on a proposed pore model. In our model, perforin monomers oligomerize having cyclic symmetry in consistent with previously found experimental constraints yet having flexibility in the size of the pore and the number of monomers involved. Clusters of the mutations on the model map to three distinct functional regions of the perforin. Calculated stability (free energy) changes show that the mutations mainly destabilize the protein structure, interestingly however, A91V polymorphism, leads to a more stable one. Structural characteristics of mutations help explain the severe functional consequences on perforin deficient patients. Our study provides a structural approach to the mutation effects on the perforin oligomerization and impaired cytotoxic function in FHL2 patients. PMID:23592409

Hemophagocytic Lymphohistiocytosis Secondary to Unknown Underlying Hodgkin Lymphoma Presenting with a Cholestatic Pattern of Liver Injury

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A.L. Booth

2018-04-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is an uncommon disease that often presents with nonspecific findings. A high index of suspicion is necessary to make a prompt diagnosis and prevent fatal disease. A 45-year-old man presented with fever, hypotension, abdominal pain, nausea, and vomiting. Imaging showed hepatosplenomegaly and laboratory tests revealed pancytopenia, increased ferritin, and a cholestatic pattern of injury with elevated alkaline phosphatase and total bilirubin. Due to a history of Crohn disease, systemic lupus erythematous, and rheumatoid arthritis, the patient was on immunosuppressants, including infliximab. After multiple negative cultures, persistent fever, and days of empiric broad spectrum antibiotics, our differential shifted to fever of unknown origin. A liver wedge biopsy revealed areas of sinusoidal dilatation with enlarged, activated macrophages containing erythrocytes and intracytoplasmic iron, consistent with hemophagocytosis due to HLH. The portal tracts showed mixed lymphoplasmacytic inflammation, a prominent bile ductular reaction, periportal fibrosis, and scattered large cells with occasional binucleation and prominent nucleoli. These cells stained positive for Epstein-Barr virus encoding region in situ hybridization, PAX5, CD15, and CD30, and hepatic involvement by classic Hodgkin lymphoma was diagnosed and determined to be the cause of the HLH and cholestatic pattern of injury. Simultaneously, a bone marrow biopsy showed diffuse involvement by Hodgkin lymphoma with a similar staining pattern. Aggressive treatment failed and the patient succumbed to multiorgan failure. HLH is a rare, potentially fatal disease, with nonspecific signs and symptoms, and should be considered in any patient presenting with fever and pancytopenia, especially if they are immune compromised.

Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients

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Samuel I. Anyanwu

2018-01-01

Full Text Available Background. Extracellular vesicles (EVs are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs in urinary EVs from HIV+ patients and compare them to HIV− samples. Methods. Urine samples were collected from HIV+ (n=35 and HIV− (n=12 individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS, and nanoparticle tracking analysis (NTA. Western blots confirmed the presence of HIV proteins. Gene ontology (GO analysis was performed using FunRich and HIV Human Interaction database (HHID. Results. EVs from urine were 30–400 nm in size. More EVs were in HIV+ patients, P<0.05, by NTA. HIV+ samples had 14,475 HPs using LC/MS/MS, while only 111 were in HIV−. HPs in the EVs were of exosomal origin. LC/MS/MS showed all HIV+ samples contained at least one HIV protein. GO analysis showed differences in proteins between HIV+ and HIV− samples and more than 50% of the published HPs in the HHID interacted with EV HIV proteins. Conclusion. Differences in the proteomic profile of EVs from HIV+ versus HIV− samples were found. HIV and HPs in EVs could be used to detect infection and/or diagnose HIV disease syndromes.

Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

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Krabbe, Simon; Gül, Cigdem; Andersen, Bjarne

2016-01-01

elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic...... lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations....

Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis-associated skin ulcers on the face and surrounding a tracheotomy stoma.

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Nagamoto, Eiko; Fujisawa, Akihiko; Yoshino, Yuichiro; Yoshitsugu, Kanako; Odo, Masashi; Watanabe, Hidetaka; Igata, Toshikatsu; Noguchi, Hiromitsu

2014-01-01

A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

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Rimma Mikhailovna Balabanova

2009-09-01

Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

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Rimma Mikhailovna Balabanova

2009-01-01

Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

Reduced baroreflex sensitivity and pulmonary dysfunction in alcoholic cirrhosis: effect of hyperoxia

DEFF Research Database (Denmark)

Møller, Søren; Iversen, J.S.; Krag, A.

2010-01-01

of hepatopulmonary syndrome (HPS). BRS is reduced at exposure to chronic hypoxia such as during sojourn in high altitudes. In this study, we assessed the relation of BRS to pulmonary dysfunction and cardiovascular characteristics and the effects of hyperoxia. Forty-three patients with cirrhosis and 12 healthy...

Assessment of the LV-S2 & LV-S3 Stack Sampling Probe Locations for Compliance with ANSI/HPS N13.1-1999

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Glissmeyer, John A.; Antonio, Ernest J.; Flaherty, Julia E.; Amidan, Brett G.

2014-09-30

This document reports on a series of tests conducted to assess the proposed air sampling locations for the Hanford Tank Waste Treatment and Immobilization Plant (WTP) Group 1-2A exhaust stacks with respect to the applicable criteria regarding the placement of an air sampling probe. The LV-C2, LV-S2, and LV-S3 exhaust stacks were tested together as a group (Test Group 1-2A). This report only covers the results of LV-S2 and LV-S3; LV-C2 will be reported on separately. Federal regulations1 require that a sampling probe be located in the exhaust stack according to the criteria established by the American National Standards Institute/Health Physics Society (ANSI/HPS) N13.1-1999, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stack and Ducts of Nuclear Facilities. 2 These criteria address the capability of the sampling probe to extract a sample that represents the effluent stream.

Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus.

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David Safronetz

2011-12-01

Full Text Available Hantavirus pulmonary syndrome (HPS, also referred to as hantavirus cardiopulmonary syndrome (HCPS, is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7-8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses.

The first whole genome sequence and pathogenicity characterization of a fowl adenovirus 4 isolated from ducks associated with inclusion body hepatitis and hydropericardium syndrome.

Science.gov (United States)

Pan, Qing; Liu, Linlin; Wang, Yongqiang; Zhang, Yanping; Qi, Xiaole; Liu, Changjun; Gao, Yulong; Wang, Xiaomei; Cui, Hongyu

2017-10-01

In June 2015, an infectious disease with high prevalence causing severe hydropericardium syndrome (HPS) first appeared in duck farms of northeast China. The disease showed high morbidity of 35% and mortality of 15% in a commercial duck farm with 200,000 45-day-old ducks. One strain of hypervirulent fowl adenovirus serotype 4 was identified and designated as HLJDAd15. The whole genome of the duck isolate was sequenced and found to contain the same large deletions as a genotype that has become prevalent in chickens in China recently, indicating that this disease might be transmitted from chickens to ducks. The pathogenicity of HLJDAd15 was evaluated in SPF chickens and ducks. The results showed that chickens were more susceptible to this new genotype of fowl adenovirus, and it was more difficult to infect ducks than chickens with the duck origin virus. Thus, it appears that this severe HPS in ducks is far more likely to have been transmitted from chickens to ducks than from ducks to ducks. Therefore, transmission from chickens to ducks constitutes a threat to the duck farming industry, and this transmission route is a very important consideration for the prevention and control of the new genotype of fowl adenovirus. This is the first whole genome sequence of a FAdV-4 isolated from ducks, and this information is important for understanding the molecular characteristics and evolution of aviadenoviruses. The potential risks of infection with this new hypervirulent FAdV-4 genotype in chickens and ducks urgently require an effective vaccine.

Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

Science.gov (United States)

Westmoreland, D; Shaw, M; Grimes, W; Metcalf, D J; Burden, J J; Gomez, K; Knight, A E; Cutler, D F

2016-04-01

Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein

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Laura eChiossone

2012-08-01

Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-γ and TNFα is present in serum. In animal models of the disease, IFN-γ and TNF-α have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-γ and TNF-α have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP resulting in an excess of free IL-18. Here we studied whether IL-18BP could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock-out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18BP treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-γ and TNF-α production by CD8+ T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18BP is beneficial in an animal model of HLH and in combination with anti-infectious therapy may be a promising strategy to treat HLH patients.

A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.

Science.gov (United States)

Bordbar, Mohammad Reza; Modarresi, Farzaneh; Farazi Fard, Mohammad Ali; Dastsooz, Hassan; Shakib Azad, Nader; Faghihi, Mohammad Ali

2017-05-03

Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.

[The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].

Science.gov (United States)

Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z

2016-07-01

To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

Actor-Network Theory as I image it. Brief essay on traffic lights La ANT tal como yo la imagino. Breve ensayo sobre el cosmos semafórico

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Carlos Enrique Silva Rios

2011-03-01

Full Text Available hps">Three years ago hps">I came hps">to hps">Barcelona hps">with hps">a firm intention hps">that I had to hps">change after hps">about two hps">months from my arrival. hps">I wanted hps">to study hps">people hps">crossing hps">the hps">street in this city hps">and then compare hps">their hps">actions hps">with hps">those of hps">the people hps">in my hps">hometown -  Caracas. hps">Since hps">carrying hps">out a comparison between hps">two hps">cities hps">was time consuming, hps

Redes do Turismo: uma análise da política de turismo do estado de Minas Gerais - Brasil

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Marcos Eduardo Carvalho Gonçalves Knupp

2012-12-01

">The state of Minas Gerais currently acts towards regionalization and decentralization of the tourism sector, integrating several municipalities that share characteristics, through Tourist Circuits. The objective of this study is to characterize the dynamics among the actors who set the Tourist Circuits in Minas Gerais. In the first stage of the survey, a macro analysis of the mineiros circuits, the data were obtained in the Tourist Circuits management organs. In the second phase interviews were made with the key actors in the Secretaria de Estado do Turismo de Minas Gerais and the Federação dos Circuitos Turísticos de Minas Gerais, identified in the first phase, in order to deepen the analysis of the interrelationship among those actors. The results obtained suggest the existence a new actor was identified who presents fundamental importance for the circuits, the existence of common and conflicting interests among actors and their negotiation spaces was also identified. Finally, it is considered that there are combined strategies among the circuits, but they are still very embryonic and that the perception of some social actors regarding the networks is very superficial.Keywords: public policy; actors networks; tourist circuits. Resumenhps">El estado de hps">Minas hps">Gerais, hps">ahora trabaja hps">para regionalizar hps">y descentralizar hps">el sector turístico hps">mediante la integración de