Sample records for combined immunodeficiency disease

  1. Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases

    Directory of Open Access Journals (Sweden)

    O. Jilkina


    Full Text Available In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70 deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ deficiency. As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID patients were studied: 1 T-negative PID (cartilage-hair hypoplasia and 4 T-positive PID (2 common immune deficiency (CID, 1 Wiskott–Aldrich syndrome, and 1 X-linked lymphoproliferative disease. Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982 were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

  2. Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases. (United States)

    Jilkina, O; Thompson, J R; Kwan, L; Van Caeseele, P; Rockman-Greenberg, C; Schroeder, M L


    In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency (SCID) is three-fold higher than the national average, with SCID overrepresented in two population groups: Mennonites and First Nations of Northern Cree ancestries. T-cell receptor excision circle (TREC) assay is being used increasingly for neonatal screening for SCID in North America. However, the majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely that the TREC assay will not identify these infants. The goal of this study was to blindly and retrospectively perform TREC analysis in confirmed SCID patients using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative SCID (3 with adenosine deaminase deficiency, 1 with CD3δ deficiency, and 1 unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ) deficiency). As a non-SCID patient group, 5 Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency (CID), 1 Wiskott-Aldrich syndrome, and 1 X-linked lymphoproliferative disease). Both patient groups required hematopoietic stem cell transplantation. In addition, randomly-selected de-identified controls (n = 982) were tested. Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in 2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified controls. Conclusions: TREC method will identify T-negative SCID and T-negative PID. To identify other SCID babies, newborn screening in Manitoba must include supplemental targeted screening for ethnic-specific mutations.

  3. Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease

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    Hema Mittal


    Full Text Available Fatal-disseminated Bacillus Calmette Guerin (BCG disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

  4. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease : A Systematic Review

    NARCIS (Netherlands)

    van der Spek, Jet; Groenwold, Rolf H. H.; van der Burg, Mirjam; van Montfrans, JM

    Background Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were reported.

  5. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

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    Sílvia Bacalhau


    Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

  6. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review

    NARCIS (Netherlands)

    J. van der Spek (Jet); R.H.H. Groenwold (Rolf H. H.); M. van der Burg (Mirjam); J.M. van Montfrans (Joris)


    textabstractBackground: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were

  7. First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature

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    Maddalena Migliavacca


    Full Text Available Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. To date, eight cases of lymphomas have been described in ADA-SCID patients. Here we report the first case of plasmablastic lymphoma occurring in a young adult with ADA-SCID on long-term ERT, which turned out to be Epstein–Barr virus associated. The patient previously received infusions of genetically modified T cells. A cumulative analysis of the eight published cases of lymphoma from 1992 to date, and the case here described, reveals a high mortality (89%. The most common form is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT. The significant incidence of immunodeficiency-associated lymphoproliferative disorders and poor survival of patients developing this complication highlight the priority in finding a prompt curative treatment for ADA-SCID.

  8. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

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    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. (Univ. of Florida College of Medicine, Gainsville, FL (United States)); George, J.F. (Univ. of Alabama, Birmingham, AL (United States)); Goodenow, M.M. (Univ. of Florida College of Medicine, Gainsville, FL (United States) Univ. of Alabama, Birmingham, AL (United States))


    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  9. Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies

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    Sanem Eren Akarcan


    Full Text Available Chronic Mucocutaneous Candidiasis (CMC is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF (c.1154 C>T, p.Thr385Met in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

  10. Learning about Severe Combined Immunodeficiency (SCID) (United States)

    Skip to main content Learning About Severe Combined Immunodeficiency (SCID) Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding ...

  11. Primary immunodeficiency diseases

    African Journals Online (AJOL)

    Complement levels are evaluated by the CH50 and AH50 – screening tests that assess the ability of the classic and alternative complement pathways respectively to haemolyse red blood cells. Reduced haemolytic activity is noted in complement factor deficiencies, but also during infections or immune complex diseases.

  12. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

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    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F. [Univ. of Pennsylvania School of Veterinary Medicine, Philadelphia, PA (United States)] [and others


    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  13. Cytotoxic T-lymphocyte-associated protein 4-Ig effectively controls immune activation and inflammatory disease in a novel murine model of leaky severe combined immunodeficiency. (United States)

    Humblet-Baron, Stéphanie; Schönefeldt, Susann; Garcia-Perez, Josselyn E; Baron, Frédéric; Pasciuto, Emanuela; Liston, Adrian


    Severe combined immunodeficiency can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as recombination-activating gene 1 (RAG1), RAG2, or DNA cross-link repair 1C (DCLRE1C). Defective DNA recombination causes a developmental block in T and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give rise to a partial loss of T cells in a spectrum including leaky severe combined immunodeficiency (LS) and Omenn syndrome (OS). These patients not only experience life-threatening infections because of immunodeficiency but also experience inflammatory/autoimmune conditions caused by the presence of autoreactive T cells. We sought to develop a preclinical model that fully recapitulates the symptoms of patients with LS/OS, including a model for testing therapeutic intervention. We generated a novel mutant mouse (Dclre1cleaky) that develops a LS phenotype. Mice were monitored for diseases, and immune phenotype and immune function were evaluated by using flow cytometry, ELISA, and histology. Dclre1cleaky mice present with a complete blockade of B-cell differentiation, with a leaky block in T-cell differentiation resulting in an oligoclonal T-cell receptor repertoire and enhanced cytokine secretion. Dclre1cleaky mice also had inflammatory symptoms, including wasting, dermatitis, colitis, hypereosinophilia, and high IgE levels. Development of a preclinical murine model for LS allowed testing of potential treatment, with administration of cytotoxic T-lymphocyte-associated protein 4-Ig reducing disease symptoms and immunologic disturbance, resulting in increased survival. These data suggest that cytotoxic T-lymphocyte-associated protein 4-Ig should be evaluated as a potential treatment of inflammatory symptoms in patients with LS and those with OS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. [Combined variable immunodeficiency with unusal features. A case report]. (United States)

    De Charry, F; Peterschmitt Tonetti, A; De Charry, C; Baseggio, L; Pasquet, F; Khenifer, S; Rassat, R; Pavic, M


    The association granulomatosis - combined variable immunodeficiency (CVID) - is well known from the clinicians. However, the association with a large granular lymphocyte (LGL) leukemia has not been yet reported. We report a 50-year-old woman, followed for CVID associated with a granulomatous disease. During the follow-up, the patient developed a granulomatous lymphocytic interstitiel lung disease (GLILD). Secondarily, she presented a LGL leukemia. To our knowledge, this is the first reported case of an association between CVID and LGL leukemia. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. [Revertant somatic mosaicism in primary immunodeficiency diseases]. (United States)

    Wada, Taizo


    Revertant somatic mosaicism has been described in an increasing number of genetic disorders including primary immunodeficiency diseases. Both back mutations leading to restoration of wild-type sequences and second-site mutations resulting in compensatory changes have been demonstrated in mosaic individuals. Recent studies identifying revertant somatic mosaicism caused by multiple independent genetic changes further support its frequent occurrence in primary immunodeficiency diseases. Revertant mosaicism acquires a particular clinical relevance because it may lead to selective growth advantage of the corrected cells, resulting in improvement of disease symptoms or atypical clinical presentations. This phenomenon also provides us unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. Here we review the recent findings of revertant somatic mosaicism in primary immunodeficiency diseases and discuss its clinical implications.

  16. Primary Immunodeficiencies Associated with EBV Disease. (United States)

    Cohen, Jeffrey I


    Epstein-Barr virus (EBV) infects nearly all humans and usually is asymptomatic, or in the case of adolescents and young adults, it can result in infectious mononucleosis. EBV-infected B cells are controlled primarily by NK cells, iNKT cells, CD4 T cells, and CD8 T cells. While mutations in proteins important for B cell function can affect EBV infection of these cells, these mutations do not result in severe EBV infection. Some genetic disorders affecting T and NK cell function result in failure to control EBV infection, but do not result in increased susceptibility to other virus infections. These include mutations in SH2D1A, BIRC4, ITK, CD27, MAGT1, CORO1A, and LRBA. Since EBV is the only virus that induces proliferation of B cells, the study of these diseases has helped to identify proteins critical for interactions of T and/or NK cells with B cells. Mutations in three genes associated with hemophagocytic lymphohistocytosis, PRF1, STXBP2, and UNC13D, can also predispose to severe chronic active EBV disease. Severe EBV infection can be associated with immunodeficiencies that also predispose to other viral infections and in some cases other bacterial and fungal infections. These include diseases due to mutations in PIK3CD, PIK3R1, CTPS1, STK4, GATA2, MCM4, FCGR3A, CARD11, ATM, and WAS. In addition, patients with severe combined immunodeficiency, which can be due to mutations in a number of different genes, are at high risk for various infections as well as EBV B cell lymphomas. Identification of proteins important for control of EBV may help to identify new targets for immunosuppressive therapies.

  17. Inflammatory Bowel Disease in Primary Immunodeficiencies. (United States)

    Kelsen, Judith R; Sullivan, Kathleen E


    Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.

  18. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)


    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of

  19. Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

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    Hanna eIJspeert


    Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

  20. Family physician perspectives on primary immunodeficiency diseases

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    Jordan eOrange


    Full Text Available Primary immunodeficiency diseases (PID include over 250 diverse disorders. The current study assessed management of PID by family practice physicians. The American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Committee and the Immune Deficiency Foundation conducted an incentivized mail survey of family practice physician members of the American Medical Association and the American Osteopathic Association in direct patient care. Responses were compared with subspecialist immunologist responses from a similar survey. Surveys were returned by 528 (of 4500 surveys mailed family practice physicians, of whom 44% reported following ≥1 patient with a PID. Selective immunoglobulin A (IgA, deficiency (21%, and chronic granulomatous disease (11% were most common and were followed by significantly more subspecialist immunologists (P<.0001. Use of intravenously administered Ig, and live viral vaccinations across PID was significantly different (P<.0001. Few family practice physicians were aware of professional guidelines for diagnosis and management of PID (4% vs. 79% of subspecialist immunologists, P<.0001. Family practice physicians will likely encounter patients with a PID diagnoses during their career. Differences in how family practice physicians and subspecialist immunologists manage patients with PID underscore areas where improved educational and training initiatives may benefit patient care.

  1. Late Onset Combined Immunodeficiency Presenting with Recurrent Pneumocystis jiroveci Pneumonia

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    Ilias Papakonstantinou


    Full Text Available Late onset combined immunodeficiency (LOCID is a recently described variant of common variable immunodeficiency (CVID, involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP, subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID. Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses.

  2. Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders

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    Hampson, F.A. [Department of Radiology, Papworth Hospital, Papworth Everard, Cambridge (United Kingdom); Chandra, A. [Department of Biochemistry and Immunology, Addenbrooke' s Hospital, Cambridge (United Kingdom); Screaton, N.J. [Department of Radiology, Papworth Hospital, Papworth Everard, Cambridge (United Kingdom); Condliffe, A. [Department of Respiratory Medicine, Addenbrooke' s Hospital, Cambridge (United Kingdom); Kumararatne, D.S. [Department of Biochemistry and Immunology, Addenbrooke' s Hospital, Cambridge (United Kingdom); Exley, A.R. [The Respiratory Infection, Inflammation and Immunology Service, Department of Immunology, Papworth Hospital, Papworth Everard, Cambridge (United Kingdom); Babar, J.L., E-mail: [Department of Radiology, Addenbrooke' s Hospital, Cambridge (United Kingdom)


    Respiratory disease is a significant cause of morbidity and mortality amongst patients with primary immunodeficiency disorders. Computed tomography (CT) plays an important role in the multidisciplinary approach to these conditions, in detecting, characterizing, and quantifying the extent of lung damage and in directing treatment. The aim of this review is to classify the primary immunodeficiency disorders and describe the thoracic complications and the associated CT findings whilst discussing the role of radiology in diagnosis and surveillance.

  3. Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and monocytopenia. (United States)

    Dotta, Laura; Badolato, Raffaele


    Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V


    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A a......A); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal....

  5. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B


    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

  6. Flow cytometry-based diagnosis of primary immunodeficiency diseases

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    Hirokazu Kanegane


    Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.

  7. Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase--deficient severe combined immunodeficiency disease patients. (United States)

    Sekhsaria, S; Fleisher, T A; Vowells, S; Brown, M; Miller, J; Gordon, I; Blaese, R M; Dunbar, C E; Leitman, S; Malech, H L


    Peripheral blood (PB) CD34+ cells mobilized by granulocyte colony-stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34+ cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34+ cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34+ cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levels of G-CSF were examined (5 and 10 micrograms/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34+ cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34+ cell counts were 57 and 76 cells/mm2 of blood (5 and 10 micrograms doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm2 of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 micrograms/kg/d, the average peak was 16 cells/mm2 of blood. For both of these patient groups mobilization of CD34+ cells to PB was impaired compared with similarly treated normal subjects (P 48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34+ cell counts and direct enumeration of PB CD34+ counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34+ cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the

  8. Exposure to Human Immunodeficiency Disease. What Precautions ...

    African Journals Online (AJOL)

    Background: The Human Immunodeficiency Virus (HIV) epidemic is more pronounced in sub-Saharan Africa. The ever-increasing prevalence of HIV infection and the continued improvement in clinical management has increased the likelihood of these patients being managed by healthcare workers. The aim of the review ...

  9. Newborn Screening for Primary Immunodeficiencies: Focus on Severe Combined Immunodeficiency (SCID and Other Severe T-Cell Lymphopenias

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    Stephan Borte


    Full Text Available Primary immunodeficiencies (PID are congenital disorders of immune competence, which are mainly characterized by a pathological susceptibility to infection. More than 240 PID disease entities have been defined so far, accounting for a broad spectrum of clinical symptoms and severity. Severe PID are increasingly becoming appreciated as a relevant health problem, and diagnostic procedures and screening profiles to allow earliest possible diagnosis on a population scale have already been developed in the USA and few European countries. The most severe PID are characterized by significant mortality in the first years of life, as well as serious morbidity with irreversible organ damage. This applies in particular to PID that are defined by the absence or functional anergy of T-lymphocytes (severe combined immunodeficiency; SCID or B-lymphocytes (e.g., X-linked agammaglobulinemia; XLA. A strategy to improve the outcome of severe PID by prompt diagnosis and immediate adequate treatment is screening newborns for the presence of T and B cells.

  10. Immunodeficiencies and autoimmune diseases: common variable immunodeficiency and Crohn-like

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    Cristina Saldaña-Dueñas

    Full Text Available Background: Common variable immunodeficiency (CVI gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%. Case report: We present the case of a patient with CVI with digestive symptoms being diagnosed of Crohn-like disease with extent ileal affectation. The main treatment of these patients is the same as classical Crohn disease although in the most severe cases, as this one, the use of immunosupresors is necessary. At this time the patient remains on clinical remmision with infliximab. She presented a previous adverse reaction with adalimumab. Discussion: The few case series in this pathology makes the treatment with immunomodulators in this immunodeficiency a real diagnostic and therapeutic challenge.

  11. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee


    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  12. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

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    Raz Somech


    Full Text Available Quantification of the T cell receptor excision circles (TRECs has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.

  13. Arterial Disease in Patients With Human Immunodeficiency Virus Infection


    Stein, James H.; Currier, Judith S.; HSUE, Priscilla Y


    With advances in antiretroviral therapy, individuals with human immunodeficiency virus (HIV) infection are living longer and increasingly die of non-HIV related diseases such as cardiovascular disease (CVD). Several observational studies suggest that HIV-infected patients on ART are at increased CVD risk; however, the precise mechanisms underlying the association between HIV infection and CVD risk are uncertain. Atherosclerosis and arterial disease in HIV-infected individuals is a multifactor...

  14. Primary Immunodeficiency Diseases and Hematopoietic Stem Cell Transplantation

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    Ayse Ozkan


    Full Text Available Hematopoietic stem cell transplantation (HSCT is the only curative therapy for primary immunodeficiency diseases. Early diagnosis, including prenatally, and early transplantation improve HSCT outcomes. Survival rates improve with advances in the methods of preparing hosts and donor cells, and in supportive and conditioning regimes.

  15. Human immunodeficiency virus/acquired immunodeficiency syndrome and tropical diseases: a Brazilian perspective

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    Morgado Mariza G


    Full Text Available The paper summarizes recent findings on the epidemiology and pathogenesis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/Aids, highlighting the role of co-infections with major tropical diseases. Such co-infections have been studied in the Brazilian context since the beginning of the Aids epidemic and are expected to be more frequent and relevant as the Aids epidemic in Brazil proceeds towards smaller municipalities and the countryside, where tropical diseases are endemic. Unlike opportunistic diseases that affect basically the immunocompromised host, most tropical diseases, as well as tuberculosis, are pathogenic on their own, and can affect subjects with mild or no immunossuppression. In the era of highly active anti-retroviral therapies (HAART, opportunistic diseases seem to be on decrease in Brazil, where such medicines are fully available. Benefiting from HAART in terms of restoration of the immune function, putative milder clinical courses are expected in the future for most co-infections, including tropical diseases. On the other hand, from an ecological perspective, the progressive geographic diffusion of Aids makes tropical diseases and tuberculosis a renewed challenge for Brazilian researchers and practitioners dealing with HIV/Aids in the coming years.

  16. Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg


    Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transpla......Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall......-transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive...... for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/ macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8-14-fold increase...

  17. Immunodeficiency among children with recurrent invasive pneumococcal disease

    DEFF Research Database (Denmark)

    Ingels, Helene; Schejbel, Lone; Lundstedt, A C


    examined. RESULTS: In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response......BACKGROUND: Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory......-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency. METHODS: Cases of rIPD in children 0-15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer...

  18. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening

    NARCIS (Netherlands)

    A.P.J. de Pagter (Anne); R.G.M. Bredius (Robbert); T.W. Kuijpers (Taco W.); J. Tramper (Jelco); M. van der Burg (Mirjam); J.M. van Montfrans (Joris); G.J.A. Driessen (Gertjan)


    textabstractSevere combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment

  19. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening.

    NARCIS (Netherlands)

    Pagter, A.P. de; Bredius, R.G.; Kuijpers, T.W.; Tramper, J.; Burg, M. van der; Montfrans, J. van; Driessen, G.J.; Flier, M. van der


    Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The

  20. Overview of 15-year severe combined immunodeficiency in the Netherlands : towards newborn blood spot screening

    NARCIS (Netherlands)

    de Pagter, Anne P. J.; Bredius, Robbert G. M.; Kuijpers, Taco W.; Tramper, Jelco; van der Burg, Mirjam; van Montfrans, JM; Driessen, Gertjan J.

    Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The

  1. 11q terminal deletion and combined immunodeficiency (Jacobsen syndrome): Case report and literature review on immunodeficiency in Jacobsen syndrome. (United States)

    Blazina, Štefan; Ihan, Alojz; Lovrečić, Luca; Hovnik, Tinka


    Antibody deficiency is common finding in patients with Jacobsen syndrome (JS). In addition, there have been few reports of T-cell defects in this condition, possibly because most of the reported patients have not been specifically evaluated for T-cell function. In this article, we present a child with an 11q deletion and combined immunodeficiency and we perform a literature overview on immunodeficiency in JS. Our patient presented with recurrent bacterial and prolonged viral infections involving the respiratory system, as well as other classic features of the syndrome. In addition to low IgM, IgG4, and B-cells, also low recent thymic emigrants, helper and naïve T-cells were found. We propose that patients with Jacobsen syndrome need thorough immunological evaluations as T-cell dysfunction might be more prevalent than previously reported. Patients with infections consistent with T-cell defects should be classified as having combined immunodeficiency. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Primary Immunodeficiency Diseases at Reference and High-Specialty Hospitals in the State of Guanajuato, Mexico

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    Eduardo Guaní-Guerra


    Full Text Available Background. In general, primary immunodeficiency diseases (PIDs are underdiagnosed in most countries. The objective of this study was to describe the frequency and clinical spectrum of PID in the most important tertiary hospitals in our region. Methods. An observational, cross-sectional, with retrospective chart, review study was conducted. A total of 26 patients were included and grouped according to the updated classification of PIDs. Results. PIDs spectra were as follows: predominantly antibody deficiency diseases were the most common category (65.38%, followed by other well-defined immunodeficiency syndromes (11.55%, congenital defects of phagocyte number and/or function (7.69%, complement deficiencies (3.85%, combined T- and B-cell immunodeficiencies (3.85%, and defects in innate immunity (3.85%. The mean time elapsed from the onset of symptoms to the reference and diagnosis by a tertiary hospital was of 4.65 ± 6.95 years. Conclusions. Predominant antibody deficiency disease was the most common group of PIDs, agreeing with international reports. Awareness of underdiagnosis by physicians is crucial for a prompt diagnosis and treatment, which in turn should improve the quality of life among patients with PIDs.

  3. Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease. (United States)

    Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A


    Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Primary immunodeficiency diseases in children: 15 year experience in a tertiary care medical center in Qatar. (United States)

    Ehlayel, Mohammad S; Bener, Abdulbari; Laban, Mohammad Abu


    Primary immunodeficiency diseases (PID) are a group of heterogeneous, rare, genetic, mainly childhood disorders that affect specific components of immune system leading to serious complications. This study is aimed at describing the prevalence and the categories of PID, the ages of onset and the diagnosis, the clinical presentations, the treatment modalities and the overall outcome of affected patients. A retrospective study was conducted on 131 pediatric patients (aged 0-14 years) diagnosed with PID at Hamad General Hospital during a 15-year period (1998-2012). Data of 131 patients (75 males & 56 females) was analyzed with an estimated prevalence of 4.7 PID patients per 100,000 children younger than 14 years of age. The most common type of PID was predominantly antibody deficiency (23.7 %), followed by other well-defined immunodeficiency syndromes (22.9 %), 19.1 % combined T and B cell immunodeficiency, but rare CVID, and no cases of complement deficiency. The mean onset age was 24.01 months and diagnosis age was 42.2 months. Recurrent infections, particularly pneumonia (48.9 %), failure to thrive (34.4 %), otitis media (26 %), sepsis (23.7 %), and chronic diarrhoea (21.4 %) were commonest presenting conditions. P. aeruginosa (15.7 %), Salmonella species (13.2 %), and Non-TB mycobacteria (13.2 %) were the most common bacterial isolates. The overall mortality rate was 21.4 % with combined immunodeficiency's accounting for 53.4 % of deaths. This study reveals that PIDs are not rare in children in Qatar; and like other studies predominantly antibody deficiencies are the most common. Strategies that reinforce awareness and education of practicing physicians, bone marrow transplantation, and establishing PID national registry should be adopted to reduce mortality and morbidity of PID patients in Qatar.

  5. Cardiovascular disease associated with human immunodeficiency virus: a review. (United States)

    Costa, Luísa Amado; Almeida, Ana G


    The cardiovascular manifestations of human immunodeficiency virus (HIV) infection have changed significantly following the introduction of highly active antiretroviral therapy (HAART) regimens. On one hand, HAART has altered the course of HIV disease, with longer survival of HIV-infected patients, and cardiovascular complications of HIV infection such as myocarditis have been reduced. On the other hand, HAART is associated with an increase in the prevalence of both peripheral and coronary arterial disease. As longevity increases in HIV-infected individuals, long-term effects, such as cardiovascular disease, are emerging as leading health issues in this population. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on epidemiology, etiopathogenesis, diagnosis, prognosis, management and therapy. Cardiovascular involvement in treatment-naive patients is still important in situations such as non-adherence to treatment, late initiation of treatment, and/or limited access to HAART in developing countries. We therefore describe the cardiovascular consequences in treatment-naive patients and the potential effect of antiretroviral treatment on their regression, as well as the metabolic and cardiovascular implications of HAART regimens in HIV-infected individuals. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  6. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy

    NARCIS (Netherlands)

    Marin, Benoît; Thiébaut, Rodolphe; Bucher, Heiner C.; Rondeau, Virginie; Costagliola, Dominique; Dorrucci, Maria; Hamouda, Osamah; Prins, Maria; Walker, Sarah; Porter, Kholoud; Sabin, Caroline; Chêne, Geneviève


    OBJECTIVE: To assess whether immunodeficiency is associated with the most frequent non-AIDS-defining causes of death in the era of combination antiretroviral therapy (cART). DESIGN: Observational multicentre cohorts. METHODS: Twenty-three cohorts of adults with estimated dates of human

  7. Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care Hospital. (United States)

    Al-Tamemi, Salem; Naseem, Shafiq Ur Rehman; Al-Siyabi, Nabila; El-Nour, Ibtisam; Al-Rawas, Abdulhakim; Dennison, David


    Primary immunodeficiency (PID) diseases are rare, complex medical disorders that often are overlooked in clinical settings. There are emerging reports of PID from Middle Eastern populations. This study describes the features of PID patients in a tertiary care setting in Oman and compares them with regional and worldwide reports. Sultan Qaboos University Hospital (SQUH) is an academic tertiary care-level hospital for specialized healthcare, including PID patients. At the time of diagnosis, patients' sociodemographics, clinical features, laboratory investigations, and management were entered in electronic form. This study included patients seen between August 2005 and July 2015. One hundred forty patients were registered with a minimum estimated population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median age of onset of symptoms was 8 months, and diagnosis was 21 months with a delay of 13 months. Family history was positive in 44 %, consanguinity was present in 76 %, death of a previous sibling was present in 36 %, and there was an overall mortality in 18 %, with an 85 % probability of survival 10 years following diagnosis. The most common type of immunodeficiency was phagocytic disorders (35.0 %), followed by predominantly antibody disorders (20.7 %), combined immunodeficiency (17.8 %), other well-defined PID syndromes (15.0 %), immune dysregulation syndromes (3.5 %), complement deficiencies (3.5 %), and unclassified immunodeficiency (4.2 %). The commonest presenting infection was pneumonia (47.1 %). PID is not a rare condition in Oman. The prevalence is in concordance with reports from the region but higher than in Western populations. The findings of the current study would help to improve the awareness and management of, and policy making for PID.

  8. Diagnostics of primary immunodeficiency diseases: a sequencing capture approach.

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    Lotte N Moens

    Full Text Available Primary Immunodeficiencies (PID are genetically inherited disorders characterized by defects of the immune system, leading to increased susceptibility to infection. Due to the variety of clinical symptoms and the complexity of current diagnostic procedures, accurate diagnosis of PID is often difficult in daily clinical practice. Thanks to the advent of "next generation" sequencing technologies and target enrichment methods, the development of multiplex diagnostic assays is now possible. In this study, we applied a selector-based target enrichment assay to detect disease-causing mutations in 179 known PID genes. The usefulness of this assay for molecular diagnosis of PID was investigated by sequencing DNA from 33 patients, 18 of which had at least one known causal mutation at the onset of the experiment. We were able to identify the disease causing mutations in 60% of the investigated patients, indicating that the majority of PID cases could be resolved using a targeted sequencing approach. Causal mutations identified in the unknown patient samples were located in STAT3, IGLL1, RNF168 and PGM3. Based on our results, we propose a stepwise approach for PID diagnostics, involving targeted resequencing, followed by whole transcriptome and/or whole genome sequencing if causative variants are not found in the targeted exons.

  9. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

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    Werner Wunderli

    Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.

  10. Refinement of linkage of human severe combined immunodeficiency (SCIDXI) to polymorphic markers in Xq13

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    Puck, J.M (Children' s Hospital of Philadelphia, PA (United States) Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)); Conely, M.E. (St. Jude Children' s Research Hospital and Univ. of Tennessee School of Medicine, Memphis (United States)); Bailey, L.C. (Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States))


    The most common form of human severe combined immunodeficiency (SCID) is inherited as an X-linked recessive genetic defect, MIM 300400. The disease locus, SCIDX1, has previously been placed in Xq13.1-q21.1 by demonstration of linkage to polymorphic markers between DXS159 and DXS3 and by exclusion from interstitial deletions of Xq21.1-q21.3. The authors report an extension of previous linkage studies, with new markers and a total of 25 SCIDX1 families including female carriers identified by nonrandom X chromosome inactivation in their T lymphocytes. SCIDX1 was nonrecombinant with DXS441, with a lod score of 17.96. Linkage relationships of new markers in the SCIDX1 families were consistent with the linkage map generated in the families of the Centre d'Etude du Polymorphisms Humain (CEPH) and with available physical map data. The most likely locus order was DXS1-(DXS159,DXS153)-DXS106-DXS132-DXS453-(SCIDX1,PGK1, DXS325,DXS347,DXS441)-DXS447-DXS72-DXYS1X-DXS3. The SCIDX1 region now spans approximately 10 Mb of DNA in Xq13; this narrowed genetic localization will assist efforts to identify gene candidates and will improve genetic management for families with SCID. 25 refs., 3 figs., 2 tabs.

  11. Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency. (United States)

    Abolhassani, Hassan; Chou, Janet; Bainter, Wayne; Platt, Craig D; Tavassoli, Mahmood; Momen, Tooba; Tavakol, Marzieh; Eslamian, Mohammad Hossein; Gharagozlou, Mohammad; Movahedi, Masoud; Ghadami, Mohsen; Hamidieh, Amir Ali; Azizi, Gholamreza; Yazdani, Reza; Afarideh, Mohsen; Ghajar, Alireza; Havaei, Arash; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Cheraghi, Taher; Behniafard, Nasrin; Amin, Reza; Aleyasin, Soheila; Faridhosseini, Reza; Jabbari-Azad, Farahzad; Nabavi, Mohammamd; Bemanian, Mohammad Hassan; Arshi, Saba; Molatefi, Rasol; Sherkat, Roya; Mansouri, Mahboubeh; Mesdaghi, Mehrnaz; Babaie, Delara; Mohammadzadeh, Iraj; Ghaffari, Javad; Shafiei, Alireza; Kalantari, Najmeddin; Ahanchian, Hamid; Khoshkhui, Maryam; Soheili, Habib; Dabbaghzadeh, Abbas; Shirkani, Afshin; Nasiri Kalmarzi, Rasoul; Mortazavi, Seyed Hamidreza; Tafaroji, Javad; Khalili, Abbas; Mohammadi, Javad; Negahdari, Babak; Joghataei, Mohammad-Taghi; Al-Ramadi, Basel K; Picard, Capucine; Parvaneh, Nima; Rezaei, Nima; Chatila, Talal A; Massaad, Michel J; Keles, Sevgi; Hammarström, Lennart; Geha, Raif S; Aghamohammadi, Asghar


    Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  12. A Markov model to analyze cost-effectiveness of screening for severe combined immunodeficiency (SCID). (United States)

    Chan, Kee; Davis, Joie; Pai, Sung-Yun; Bonilla, Francisco A; Puck, Jennifer M; Apkon, Michael


    To evaluate the cost-effectiveness of universal neonatal screening for T cell lymphocytopenia in enhancing quality of life and life expectancy for children with severe combined immunodeficiency (SCID). Decision trees were created and analyzed to estimate the cost, life years, and quality adjusted life years (QALYs) across a population when universal screening for lack of T cells is used to detect SCID, as implemented in five states, compared to detection based on recognizing symptoms and signs of disease. Terminal values of each tree limb were derived through Markov models simulating the natural history of three cohorts: unaffected subjects; those diagnosed with SCID as neonates (early diagnosis); and those diagnosed after becoming symptomatic and arousing clinical suspicion (late diagnosis). Models considered the costs of screening and of care including hematopoietic cell transplantation for affected individuals. Key decision variables were derived from the literature and from a survey of families with children affected by SCID, which was used to describe the clinical history and healthcare utilization for affected subjects. Sensitivity analyses were conducted to explore the influence of these decision variables. Over a 70-year time horizon, the average cost per infant was $8.89 without screening and $14.33 with universal screening. The model predicted that universal screening in the U.S. would cost approximately $22.4 million/year with a gain of 880 life years and 802 QALYs. Sensitivity analyses showed that screening test specificity and disease incidence were critical driving forces affecting the incremental cost-effectiveness ratio (ICER). Assuming a SCID incidence of 1/75,000 births and test specificity and sensitivity each at 0.99, screening remained cost-effective up to a maximum cost of $15 per infant screened. At our current estimated screening cost of $4.22/infant, universal screening for SCID would be a cost effective means to improve quality and

  13. Primary Immunodeficiency Diseases in Highly Consanguineous Populations from Middle East and North Africa: Epidemiology, Diagnosis, and Care

    Directory of Open Access Journals (Sweden)

    Hamoud Al-Mousa


    Full Text Available Middle East and North Africa region (MENA1 populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance. Studies of PIDs in the region had contributed into the discovery and the understanding of several novel immunodeficiency disorders. Few MENA countries have established national registries that helped in estimating the prevalence and defining common PID phenotypes. Available reports from those registries suggest a predominance of combined immunodeficiency disorders in comparison to antibody deficiencies seen in other populations. Access to a comprehensive clinical immunology management services is limited in most MENA countries. Few countries had established advanced clinical immunology service, capable to provide extensive genetic testing and stem cell transplantation for various immunodeficiency disorders. Newborn screening for PIDs is an essential need in this population considering the high incidence of illness and can be implemented and incorporated into existing newborn screening programs in some MENA countries. Increased awareness, subspecialty training in clinical immunology, and establishing collaborating research centers are necessary to improve patient care. In this review, we highlight some of the available epidemiological data, challenges in establishing diagnosis, and available therapy for PID patients in the region.

  14. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

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    Claudia A Montiel-Equihua


    Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

  15. Chimerism in a child with severe combined immunodeficiency: a case report. (United States)

    Aureli, Anna; Piancatelli, Daniela; Monaco, Palmina I; Ozzella, Giuseppina; Canossi, Angelica; Piazza, Antonina; Isacchi, Giancarlo; Caniglia, Maurizio; Adorno, Domenico


    Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T-lymphocyte and B-lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one-year-old boy with SCID.

  16. Pegademase bovine (PEG-ADA for the treatment of infants and children with severe combined immunodeficiency (SCID

    Directory of Open Access Journals (Sweden)

    Claire Booth


    Full Text Available Claire Booth1,2, H Bobby Gaspar1,21Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK; 2Dept of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UKAbstract: Adenosine deaminase deficiency (ADA is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID, a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT with pegademase bovine (PEG-ADA and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.Keywords: adenosine deaminase deficiency, PEG-ADA, enzyme replacement therapy, severe combined immune deficiency (SCID

  17. Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

    Directory of Open Access Journals (Sweden)

    Smriti Kundu-Raychaudhuri


    Full Text Available Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

  18. Advances of gene therapy for primary immunodeficiencies


    Fabio Candotti


    In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanc...

  19. Rapidly progressive periodontal disease associated with human immunodeficiency virus. (United States)

    Al-Hezaimi, Khalid; Javed, Fawad; Ali, Tazeen Saeed; Al-Askar, Mansour; Al-Rasheed, Abdulaziz


    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and interdental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to indentify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction.

  20. Fatal respiratory distress syndrome due to coronavirus infection in a child with severe combined immunodeficiency. (United States)

    Szczawinska-Poplonyk, Aleksandra; Jonczyk-Potoczna, Katarzyna; Breborowicz, Anna; Bartkowska-Sniatkowska, Alicja; Figlerowicz, Magdalena


    Coronaviruses have been demonstrated to contribute substantially to respiratory tract infections among the child population. Though infected children commonly present mild upper airway symptoms, in high-risk patients with underlying conditions, particularly in immunocompromised children these pathogens may lead to severe lung infection and extrapulmonary disorders. In this paper, we provide the first report of the case of a 15-month-old child with severe combined immunodeficiency and coronavirus HKU1-related pneumonia with fatal respiratory distress syndrome. © 2012 John Wiley & Sons Ltd.

  1. Myelofibrosis in severe combined immunodeficiency due to vitamin D deficiency rickets. (United States)

    al-Eissa, Y A; al-Mashhadani, S A


    An infant with severe combined immunodeficiency is described in whom a refractory anemia and thrombocytopenia developed after the age of 6 months, associated with poor growth and frequent episodes of upper respiratory tract infections and diarrhea. He required frequent blood and platelet transfusions. Bone marrow biopsy provided evidence that the anemia and thrombocytopenia were the results of myelofibrosis which was secondary to vitamin D deficiency. Therapy with 1,25-dihydroxycholecalciferol resulted in resolution of the hematologic and skeletal abnormalities, but he remained susceptible to recurrent serious infections and died at the age of 13 months.

  2. The novel capripoxvirus vector lumpy skin disease virus efficiently boosts modified vaccinia Ankara human immunodeficiency virus responses in rhesus macaques. (United States)

    Burgers, Wendy A; Ginbot, Zekarias; Shen, Yen-Ju; Chege, Gerald K; Soares, Andreia P; Müller, Tracey L; Bunjun, Rubina; Kiravu, Agano; Munyanduki, Henry; Douglass, Nicola; Williamson, Anna-Lise


    Poxvirus vectors represent promising human immunodeficiency virus (HIV) vaccine candidates and were a component of the only successful HIV vaccine efficacy trial to date. We tested the immunogenicity of a novel recombinant capripoxvirus vector, lumpy skin disease virus (LSDV), in combination with modified vaccinia Ankara (MVA), both expressing genes from HIV-1. Here, we demonstrated that the combination regimen was immunogenic in rhesus macaques, inducing high-magnitude, broad and balanced CD4(+) and CD8(+) T-cell responses, and transient activation of the immune response. These studies support further development of LSDV as a vaccine vector. © 2014 The Authors.

  3. Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome

    NARCIS (Netherlands)

    Cliffe, S.T.; Bloch, D.B.; Suryani, S.; Kamsteeg, E.J.; Avery, D.T.; Palendira, U.; Church, J.A.; Wainstein, B.K.; Trizzino, A.; Lefranc, G.; Akatcherian, C.; Megarbane, A.; Gilissen, C.; Moshous, D.; Reichenbach, J.; Misbah, S.; Salzer, U.; Abinun, M.; Ong, P.Y.; Stepensky, P.; Ruga, E.; Ziegler, J.B.; Wong, M.; Tangye, S.G.; Lindeman, R.; Buckley, M.F.; Roscioli, T.


    BACKGROUND: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic

  4. Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang


    Full Text Available Mutations of the Janus family kinase JAK3 gene cause severe combined immunodeficiency (SCID. JAK3 deficiency in humans is characterized by the absence of circulating T cells and natural killer (NK cells with normal numbers of poorly functioning B cells (T–B+NK–. Using SCID patient-specific induced pluripotent stem cells (iPSCs and a T cell in vitro differentiation system, we demonstrate a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor (TCR repertoire. Whole-genome sequencing of corrected cells demonstrates no CRISPR/Cas9 off-target modifications. These studies describe an approach for the study of human lymphopoiesis and provide a foundation for gene correction therapy in humans with immunodeficiencies.

  5. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Directory of Open Access Journals (Sweden)

    Satoshi Horino

    Full Text Available X-linked severe combined immunodeficiency (SCID-X1 is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc gene, and characterized by a complete defect of T and natural killer (NK cells. Gene therapy for SCID-X1 using conventional retroviral (RV vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  6. Management of a rare presentation of Vogt-Koyanagi-Harada disease in human immunodeficiency virus/acquired immunodeficiency disease syndrome patient

    Directory of Open Access Journals (Sweden)

    D Priya


    Full Text Available Vogt-Koyanagi-Harada (VKH, a multisystem autoimmune bilateral panuveitis with systemic manifestations, is uncommon in immunocompromised patients such as human immunodeficiency virus (HIV/acquired immunodeficiency disease syndrome (AIDS. We report a rare presentation of VKH in a 45-year-old HIV-positive female on highly active antiretroviral therapy (HAART who presented with a history of recurrent panuveitis. A diagnosis of probable VKH was made based on ocular and systemic signs and symptoms. She was treated with topical and systemic steroids with close monitoring of CD4 counts and viral loads. After inflammation control, complicated cataract was managed surgically under perioperative steroid cover. VKH in HIV/AIDS has not been reported earlier. This case shows that significant inflammation can be seen even in HIV/AIDS patients on HAART with VKH in spite of moderate CD4 counts. Management is a challenge considering the systemic risks with long-term use of steroids.

  7. Management of a rare presentation of Vogt-Koyanagi-Harada disease in human immunodeficiency virus/acquired immunodeficiency disease syndrome patient. (United States)

    Priya, D; Sudharshan, S; Biswas, Jyotirmay


    Vogt-Koyanagi-Harada (VKH), a multisystem autoimmune bilateral panuveitis with systemic manifestations, is uncommon in immunocompromised patients such as human immunodeficiency virus (HIV)/acquired immunodeficiency disease syndrome (AIDS). We report a rare presentation of VKH in a 45-year-old HIV-positive female on highly active antiretroviral therapy (HAART) who presented with a history of recurrent panuveitis. A diagnosis of probable VKH was made based on ocular and systemic signs and symptoms. She was treated with topical and systemic steroids with close monitoring of CD4 counts and viral loads. After inflammation control, complicated cataract was managed surgically under perioperative steroid cover. VKH in HIV/AIDS has not been reported earlier. This case shows that significant inflammation can be seen even in HIV/AIDS patients on HAART with VKH in spite of moderate CD4 counts. Management is a challenge considering the systemic risks with long-term use of steroids.

  8. Evaluation of performance of human immunodeficiency virus antigen/antibody combination assays in Taiwan. (United States)

    Chang, Chun-Kai; Kao, Cheng-Feng; Lin, Pi-Han; Huang, Hui-Lin; Ho, Shu-Yuan; Wong, Kuo-Chen; Lin, Bo-Chang; Yeh, Chang-Ching; Lee, Chia-Yeh; Kao, Chuan-Liang; Lee, Chun-Nan; Chang, Sui-Yuan; Yang, Jyh-Yuan


    The fourth-generation human immunodeficiency virus (HIV) combination assay, which can simultaneously detect the presence of anti-HIV antibody and HIV antigen, has been shown to shorten the window period in HIV diagnosis compared with the third-generation HIV antibody immunoassay. This study was aimed to determine the performance of HIV combination assays in Taiwan, where the HIV-1 seroprevalence is 0.007% and HIV-2 infection has never been reported. Performance of three fourth-generation HIV Ag/Ab combination assays (Dia.Pro, Wantai, and Bio-Rad) and one third-generation HIV Ab immunoassay (AxSYM HIV 1/2 gO) was assessed. A total of 152 specimens, including 86 confirmed HIV-seropositive and 66 HIV-seronegative samples, were used in the study. The sensitivity of four assays varied from 98.8% to 100%, and specificity varied from 98.5% to 100%. Performance of the 75 equivocal samples, the HIV status of which was confirmed later, in terms of negative prediction varied from 81.8% to 87.5%. The Bio-Rad and Dia.Pro assays exhibited higher sensitivity for the detection of p24 antigen among the three fourth-generation HIV combination assays. The three fourth-generation HIV Ag/Ab combination assays exhibited better sensitivity, specificity, and negative prediction than the third-generation HIV Ab immunoassay. Copyright © 2015. Published by Elsevier B.V.

  9. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings. (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte


    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  10. Abnormal in vitro thymocyte differentiation in a patient with severe combined immunodeficiency-Nezelof`s syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Knutsen, A.P.; Wall, D.; Mueller, K.R.; Bouhasin, J.D. [Pediatric Research Institute, St. Louis, MO (United States)


    An in vitro coculture model system of CD34+ stem cells and allogenic cultured thymic epithelia fragments was used to evaluate thymocyte differentiation in a 9-month-old child of Amish descent with Nezelof syndrome. Though the patient`s stem cells differentiate to acquire normal expression of CD2 and CD7, later steps of maturation were abnormal. There was detectable but reduced expression of CD3 and CD4 phenotypes. CD44+ expression, however, was markedly reduced. CD44 is an adhesion molecule, interacting with the matrix ligands hyaluronan and fibronectin, and is expressed early in thymocyte differentiation and subsequently in mature T cells. It is hypothesized that abnormal expression of CD44 in a variant of severe combined immunodeficiency, Nezelof`s syndrome, interferes with normal thymocyte and thymic epithelial interaction, which leads to abnormal thymocyte differentiation. 35 refs., 2 figs., 3 tabs.

  11. Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Nikola Schlechter


    Full Text Available Primary immunodeficiency disorders (PIDs render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG vaccination and dissemination in combined immunodeficiencies. Varied phenotype expression poses a challenge to identification of the putative immune deficit. Without the availability of genomic diagnosis and data analysis resources and with limited capacity for functional definition of immune pathways, it is difficult to establish a definitive diagnosis and to decide on appropriate treatment. This study describes the use of exome sequencing to identify a homozygous recessive variant in MAP3K14, NIKVal345Met, in a patient with combined immunodeficiency, disseminated BCG-osis, and paradoxically elevated lymphocytes. Laboratory testing confirmed hypogammaglobulinemia with normal CD19, but failed to confirm a definitive diagnosis for targeted treatment decisions. NIKVal345Met is predicted to be deleterious and pathogenic by two in silico prediction tools and is situated in a gene crucial for effective functioning of the non-canonical nuclear factor-kappa B signaling pathway. Functional analysis of NIKVal345Met- versus NIKWT-transfected human embryonic kidney-293T cells showed that this mutation significantly affects the kinase activity of NIK leading to decreased levels of phosphorylated IkappaB kinase-alpha (IKKα, the target of NIK. BCG-stimulated RAW264.7 cells transfected with NIKVal345Met also presented with reduced levels of phosphorylated IKKα, significantly increased p100 levels and significantly decreased p52 levels compared to cells transfected

  12. Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell-induced inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Brimnes, J; Reimann, J


    Scid mice transplanted either with a gut wall graft or with low numbers of purified CD4+ T cells from immunocompetent syngeneic donor mice show clinical signs of IBD 3-4 months post-transplantation. The disease is mediated by mucosa-infiltrating CD4+ TCR alphabeta+ T cells. The pathology of 52...... individual colon segments obtained from 20 gut wall- or CD4+ T cell-transplanted diseased scid mice was evaluated by histology and the numbers of infiltrating immunoglobulin-containing cells were determined. In particular, cells positive for IgM, IgA and non-inflammatory immunoglobulin isotypes such as IgG1...... and IgG2b were found to accumulate in colon segments displaying the most severe histopathology, including inflammatory cellular infiltration, epithelial hyperplasia and ulcerative lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid colon shows increased levels of cells positive...

  13. Failure of lymphocyte-membrane HLA-A and -B expression in two siblings with combined immunodeficiency

    NARCIS (Netherlands)

    Schuurman, R.K.B.; Rood, J.J. van; Vossen, J.M.; Schellekens, P.Th.A.; Feltkamp-Vroom, Th.M.; Doyer, E.; Gmelig Meyling, F.H.J.; Visser, H.K.A.


    A diagnosis of partial combined immunodeficiency was made in two Turkish siblings with a history of multiple pyogenic infections and persistent candidiasis. They demonstrated severe hypo-γ-globulinemia, with B-lymphocytes, but deficient plasma cell differentiation. T-Lymphocytes were decreased in

  14. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene (United States)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  15. The functional state of follicular dendritic cells in severe combined immunodeficient (SCID) mice: role of the lymphocytes

    NARCIS (Netherlands)

    Yoshida, K.; van den Berg, T. K.; Dijkstra, C. D.


    In the present study, we have investigated the capacity of follicular dendritic cells (FDC) to trap immune complexes (IC) in the splenic white pulp of severe combined immunodeficient (SCID) mice and the influence of lymphocyte transfer on FDC function. FDC are absent in the splenic white pulp of

  16. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency

    DEFF Research Database (Denmark)

    Abolhassani, Hassan; Edwards, Emily S. J.; Ikinciogullari, Aydan


    In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma and hypogammaglo...

  17. Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Deschenes, S.M.; Puck, J.M.; Dutra, A.S. [Univ. of Pennsylvania School of Medicine and Children`s Hospital of Philadelphia, PA (United States)] [and others


    Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly (TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly (CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the {gamma} chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification. 35 refs., 4 figs., 1 tab.

  18. A New Face of Cardiac Emergencies: Human Immunodeficiency Virus-Related Cardiac Disease. (United States)

    Tsabedze, Nqoba; Vachiat, Ahmed; Zachariah, Don; Manga, Pravin


    The human immunodeficiency virus epidemic is a major health challenge of the twenty-first century as the transition from infectious complications to noncommunicable disease becomes more evident. These patients may present to the emergency department with a variety of cardiovascular diseases, such as acute coronary syndromes, heart failure, pericardial disease, infective endocarditis, venothromboembolism, and other conditions. Increased awareness is needed among health care professionals to enhance adequate identification and promote prompt management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Newborn Screening for Severe Combined Immunodeficiency-A History of the TREC Assay

    Directory of Open Access Journals (Sweden)

    Mary T. Bausch-Jurken


    Full Text Available Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay. The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.

  20. [Chagas disease and immunodeficiency: HIV infection and transplantation]. (United States)

    Le Loup, G; Ibrahim, K; Malvy, D


    In the immunocompromised patients, the main features of Chagas disease are severe clinical manifestations during the acute phase and reactivations occurring during the chronic phase. Reactivation is defined by a demonstration of trypomastigots on microscopic examination of blood or the identification of amastigots on biopsy samples and/or acute clinical manifestations during the chronic phase. In HIV patients, meningo-encephalitis and myocarditis are the major clinical syndromes of reactivation. In transplanted patients, cutaneous lesions often reveal the reactivation. A parasiticidal treatment (nifurtimox or benznidazole) should be initiated immediately. A secondary prophylaxis is indicated for HIV patients with CD4 cells count < 200/mm3. In the near future, quantitative PCR could allow to diagnose early reactivation, to initiate preemptive therapy and to closely monitor the therapeutic response. Due to the severe manifestations and prognosis of Chagas disease in the immunocompromised host, two serologic tests must be performed in the patient with an history of residency in endemic countries.

  1. Combination vaccines against diarrheal diseases. (United States)

    Venkatesan, Malabi M; Van de Verg, Lillian L


    Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. Despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and Salmonella typhi-based vaccines for typhoid fever. The recognition of the impact of diarrheal episodes on infant growth, as seen in resource-poor countries, has spurred action from governmental and non-governmental agencies to accelerate research toward affordable and effective vaccines against diarrheal diseases. Both travelers and children in endemic countries will benefit from a combination diarrheal vaccine, but it can be argued that the greater proportion of any positive impact will be on the public health status of the latter. The history of combination pediatric vaccines indicate that monovalent or single disease vaccines are typically licensed first prior to formulation in a combination vaccine, and that the combinations themselves undergo periodic revision in response to need for improvement in safety or potential for wider coverage of important pediatric pathogens. Nevertheless combination pediatric vaccines have proven to be an effective tool in limiting or eradicating communicable childhood diseases worldwide. The landscape of diarrheal vaccine candidates indicates that there now several in active development that offer options for potential testing of combinations to combat those bacterial and viral pathogens responsible for the heaviest disease burden-rotavirus, ETEC, Shigella, Campylobacter, V. cholera and Salmonella.

  2. Recombination activating gene-2null severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently (United States)

    Choi, Yun-Jung; Kim, EunSu; Reza, Abu Musa Md Talimur; Hong, Kwonho; Song, Hyuk; Park, Chankyu; Cho, Seong-Keun; Lee, Kiho; Prather, Randall S.; Kim, Jin-Hoi


    This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3+-, CD4+-, and CD8+ signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice. Further, NK cell maturation-related gene expression was significantly lower in RAG-2 SCID pigs than in Rag-2 SCID mice. Consistently, the RAG-2 SCID pigs, but not Rag-2 SCID mice, developed human induced pluripotent stem cell-derived teratomas that were the same as those of perforin/Rag-2 SCID mice. Therefore, these unexpected findings indicate the superiority of RAG-2 SCID pigs over Rag-2 SCID mice as a suitable model for investigating human diseases. PMID:29050212

  3. Successful treatment of human immunodeficiency virus-related Castleman's disease: a case report and literature review. (United States)

    Liberopoulos, Evagelos; Tolis, Christos; Bai, Mary; Efremidis, Stavros; Pavlidis, Nikolaos; Elisaf, Moses


    Multicentric Castleman's disease is increasingly recognized as an aggressive illness with a rapidly fatal outcome in human immunodeficiency virus (HIV)-infected patients. In the absence of optimal therapy, various therapeutic interventions have been tested with disappointing results; only five reports with a successful outcome have been described. Presented herein is a 66-year-old HIV-infected man with multicentric Castleman's disease. Early administration of cyclophosphamide, doxorubicin, vincristine and prednisone resulted in prolonged clinical recovery. The relevant literature is also reviewed. Copyright 2003 S. Karger AG, Basel

  4. Recombination activating gene-2null severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently


    Choi, Yun-Jung; Kim, Eunsu; Reza, Abu Musa Md Talimur; Hong, Kwonho; Song, Hyuk; Park, Chankyu; Cho, Seong-Keun; Lee, Kiho; Prather, Randall S.; Kim, Jin-Hoi


    This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3+-, CD4+-, and CD8+ signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFAT...

  5. Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency. (United States)

    Bacchelli, Chiara; Moretti, Federico A; Carmo, Marlene; Adams, Stuart; Stanescu, Horia C; Pearce, Kerra; Madkaikar, Manisha; Gilmour, Kimberly C; Nicholas, Adeline K; Woods, C Geoffrey; Kleta, Robert; Beales, Phil L; Qasim, Waseem; Gaspar, H Bobby


    Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells. We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers. A novel homozygous frameshift mutation in the gene encoding for LAT was identified in this kindred. Genetic, molecular, and functional analyses were used to identify and characterize the LAT defect. Clinical and immunologic analysis of patients was also performed and reported. Homozygosity mapping was used to identify potential defective genes. Sanger sequencing of the LAT gene showed a mutation that resulted in a premature stop codon and protein truncation leading to complete loss of function and loss of expression of LAT in the affected family members. We also demonstrate loss of LAT expression and lack of TCR signaling restoration in LAT-deficient cell lines reconstituted with a synthetic LAT gene bearing this severe combined immunodeficiency mutation. For the first time, the results of this study show that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Irradiated fetal thymus transplantation in a patient with combined immunodeficiency with predominant T cell defect

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Shigenori; Yanabe, Yasuhide; Tsuchiya, Hiroyuki; Akahoshi, Izumi; Migita, Masahiro; Matsuda, Ichiro (Kumamoto Univ. (Japan). School of Medicine); Udaka, Keiji


    A 6 month old boy was diagnosed as a case of combined immunodeficiency (with predominant T cell defect by previous classification). His T cell count was decreased, his B cell count in peripheral blood was increased, his serum IgG level was decreased, his serum IgM level was normal and the thymus was not evident on CT scans and magnetic resonance imaging. Administration of the thymus hormone, thymosin, led to a partial recovery of T cell function without normalization of the T cell count. At age 26 months the patient received an irradiated thymus transplantation from a 16 week old female fetus. After the transplantation, the T cell count (mainly CD4[sup +] cells) increased by 50-70%. A mild graft-versus-host reaction (GVHR) occurred and several immunosuppressants were prescribed. Chromosome analysis showed that the T cells have both 46 XY and 46 XX karyotypes while the B cells have the 46 XY karyotype alone. His cellular immunity (skin tests, DNA synthesis, mixed lymphocyte reaction, cytotoxic activity and natural killer cell function) and his serum IgG level remained low. However, being on regular [gamma]-globulin therapy and oral anti-fungal drugs, he is now living normally with almost no trouble at age 6 years and 3 months. This case showed that irradiated thymus transplantation might be a useful method when an adequate donor for bone marrow transplantation is not available. The unexpected observation that the increased T cells were mainly CD4 may be related to the mild GVHR and the clinical improvement. (author).

  7. Cardiovascular disease in human immunodeficiency virus-infection as a cause of hospitalization: a case-series in a General Hospital in Peru

    Directory of Open Access Journals (Sweden)

    Germán Valenzuela-Rodríguez


    Conclusions: Cardiovascular disease is an important cause of hospitalization in Peruvian human immunodeficiency virus patients, with differences between immunosuppression stages. Further studies analyzing associated factors are warranted.

  8. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. (United States)

    Kwan, Antonia; Abraham, Roshini S; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E; Bonilla, Francisco A; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A; Comeau, Anne Marie; Connelly, James A; Cowan, Morton J; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W; Hale, Jaime E; Hanson, I Celine; Hay, Beverly N; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M; Kohn, Donald B; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B; Naides, Stanley J; Notarangelo, Luigi D; Orange, Jordan S; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A; Scott, Ginger; Scott, Patricia M; Secord, Elizabeth; Seroogy, Christine; Shearer, William T; Siegel, Subhadra; Silvers, Stacy K; Stiehm, E Richard; Sugerman, Robert W; Sullivan, John L; Tanksley, Susan; Tierce, Millard L; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E; Wasserman, Richard L; Watson, Michael S; Weinberg, Geoffrey A; Weiner, Leonard B; Wood, Heather; Yates, Anne B; Puck, Jennifer M; Bonagura, Vincent R


    Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. Epidemiological and retrospective observational study. Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection

  9. Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States (United States)

    Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.


    IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in

  10. Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease. (United States)

    Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella


    Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  11. Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease

    Directory of Open Access Journals (Sweden)

    Suzanne Skoda-Smith


    Full Text Available Suzanne Skoda-Smith, Troy R Torgerson, Hans D OchsSeattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, WashingtonAbstract: Antibody deficiency is the most frequently encountered primary immunodeficiency disease (PIDD and patients who lack the ability to make functional immunoglobulin require life-long replacement therapy to prevent serious bacterial infections. Human serum immunoglobulin manufactured from pools of donated plasma can be administered intramuscularly, intravenously or subcutaneously. With the advent of well-tolerated preparations of intravenous immunoglobulin (IVIg in the 1980s, the suboptimal painful intramuscular route of administration is no longer used. However, some patients continued to experience unacceptable adverse reactions to the intravenous preparations, and for others, vascular access remained problematic. Subcutaneously administered immunoglobulin (SCIg provided an alternative delivery method to patients experiencing difficulties with IVIg. By 2006, immunoglobulin preparations designed exclusively for subcutaneous administration became available. They are therapeutically equivalent to intravenous preparations and offer patients the additional flexibility for the self-administration of their product at home. SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life.Keywords: subcutaneous immunoglobulin, primary immunodeficiency disease, antibody deficiency, X-linked agammaglobulinemia, common variable immune deficiency

  12. The Burden of Smoking in the Health-Disease Process in People with Human Immunodeficiency Virus and AIDS

    Directory of Open Access Journals (Sweden)

    Yoenny Peña García


    Full Text Available Foundation: smoking affects individual, familial and social health of people living with the human immunodeficiency virus and AIDS. The effects of the habit on these patients influence morbidity and mortality and increase the risk of various diseases and affect the immune response to antiretroviral treatment. Objective: to determine the burden of smoking on the disease health process in patients living with human immunodeficiency virus and AIDS. Methods: an analytical cohort study was performed. It was analyzed as a dependent variable for smoking in people living with the human immunodeficiency virus and AIDS, and as independent variables: age, years of exposure (as a smoker, diseases that have suffered in the last 5 years, immunological condition, and response to antiretroviral therapy. The relative risk and the etiologic risk fraction were calculated, as well as the Chi2 test to estimate the strength of association between the independent and dependent variables. Results: smoking in patients living with human immunodeficiency virus and AIDS had a significant statistical association with different related effects, which in order of strength of association increases the risk of deterioration of the immune system and the incidence of malignant tumours and pneumonia Pneumocystis jirovecii. Conclusion: there was a causal relationship between smoking and the immunodeficiency virus in addition to the incidence of Pneumocystis jirovecii pneumonia. It was show that smoking impairs the immune condition of these patients and affects the adequate response to antiretroviral treatment.

  13. Medical Devices; Immunology and Microbiology Devices; Classification of the Newborn Screening Test for Severe Combined Immunodeficiency Disorder. Final order. (United States)


    The Food and Drug Administration (FDA or we) is classifying the newborn screening test for severe combined immunodeficiency disorder (SCID) into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the newborn screening test for SCID's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  14. Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency (United States)

    Wolf, Dana G.; Yaniv, Isaac; Ashkenazi, Shai; Honigman, Alik


    Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. These unique findings may be related to the nature of the immunodeficiency in the SCID patient. PMID:11158760

  15. Case Report: Whole exome sequencing identifies variation c.2308G>A p.E770K in RAG1 associated with B- T- NK+ severe combined immunodeficiency [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Geeta Madathil Govindaraj


    Full Text Available Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating genes RAG 1 and RAG 2 are associated with a range of clinical presentations including, severe combined immunodeficiency and autoimmunity. Recently, our understanding of the molecular basis of immune dysfunction in RAG deficiency has improved tremendously with newer insights into the ultrastructure of the RAG complex. In this report, we describe the application of whole exome sequencing for arriving at a molecular diagnosis in a child suffering from B- T- NK+ severe combined immunodeficiency. Apart from making the accurate molecular diagnosis, we also add a genetic variation c.2308G>A p.E770K to the compendium of variations associated with the disease.

  16. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

    NARCIS (Netherlands)

    T.W. Kuijpers (Taco W.); E.M.M. van Leeuwen (Ester); B.H. Barendregt (Barbara); P. Klarenbeek (Paul); D.J. Aan de Kerk (Daan); P.A. Baars (Paul); M.H. Jansen (Machiel H.); N. de Vries (Nicolette); R.A.W. van Lier (Rene); M. van der Burg (Mirjam)


    textabstractMutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B+T-NK-X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

  17. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

    NARCIS (Netherlands)

    Kuijpers, Taco W.; van Leeuwen, Ester M. M.; Barendregt, Barbara H.; Klarenbeek, Paul; Aan de Kerk, Daan J.; Baars, Paul A.; Jansen, Machiel H.; de Vries, Niek; van Lier, René A. W.; van der Burg, Mirjam


    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

  18. Malignancies and infection due to the human immunodeficiency virus. Are these emerging diseases? (United States)

    Valencia Ortega, M E


    Since the start of the human immunodeficiency virus (HIV) epidemic, tumour disease among patients has been significant. The collection of malignancies can be divided primarily into 2 groups: those associated with HIV (all of which are related to viral diseases) and those not associated with HIV (only some of which are associated with viral diseases). The origin of these malignancies is multifactorial, and the main causes that have led to an increase in tumour disease are immunosuppression, coinfection with oncogenic viruses and life prolongation secondary to the use of antiretroviral therapy. Establishing the general characteristics of the undiagnosed AIDS tumours is difficult, mainly because they are a highly heterogeneous group formed by malignancies of a diverse nature. The treatments do not differ from those used in the general population, although the management can be more difficult due to the late diagnosis, drug interactions and associated comorbidities. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  19. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era (United States)

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi


    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944

  20. Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives

    National Research Council Canada - National Science Library

    Errante, Paolo Ruggero; Franco, José Luis; Espinosa‐Rosales, Francisco Javier; Sorensen, Ricardo; Condino‐Neto, Antonio


    .... The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational...

  1. Primary Immunodeficiency Diseases in Aguascalientes, Mexico: Results from an Educational Program. (United States)

    Alvarez-Cardona, Aristoteles; Espinosa-Padilla, Sara Elva; Reyes, Saul Oswaldo Lugo; Ventura-Juarez, Javier; Lopez-Valdez, Jaime Asael; Martínez-Medina, Lucila; Santillan-Artolozaga, Alberto; Cajero-Avelar, Adriana; De Luna-Sosa, Alma R; Torres-Bernal, Luis F; Espinosa-Rosales, Francisco J


    Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders characterized mainly by recurrent infections. Late diagnosis remains as one of the main issues to solve. We aimed to increase PID diagnosis in Aguascalientes, a 1.3 million inhabitants state in the center of Mexico, and to describe the clinical features of such patients. We developed an educational program for health personnel and general public; patients with possible PID were referred to a State University clinical center from December 2011 to December 2012. The patients were evaluated at the clinic and their definitive diagnosis pursued through laboratory, molecular and genetic assays. We describe the findings of those patients and analyze the impact of the program in terms of number of referrals. After 41 talks and 12 media appearances 151 patients were referred for evaluation. Fifteen (9.9%) were diagnosed with PID: five (33%) had antibody deficiencies, seven (47%) Well-defined syndromes, two (13%) Severe combined Immunodeficiency (SCID) and one case (7%) of an innate immune deficiency. All of the 15 PID patients had been referred by physicians, as opposed to the public. We estimated a "number needed to teach" of 75 physicians to get one PID patient referral. Educational programs are a fundamental part of the global efforts to increase PID diagnosis and care. To be successful, such programs should include public relations, reach for first-contact physicians, and aim to develop an efficient referral network with molecular diagnostic capability. Enhancing medical knowledge on PID is a successful strategy to improve early diagnosis and treatment.

  2. Early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Viskam Wijewardana


    Full Text Available Myeloid dendritic cells (mDC are lost from blood in individuals with human immunodeficiency virus (HIV infection but the mechanism for this loss and its relationship to disease progression are not known. We studied the mDC response in blood and lymph nodes of simian immunodeficiency virus (SIV-infected rhesus macaques with different disease outcomes. Early changes in blood mDC number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable infection that remained disease-free for more than one year had average increases in blood mDC of 200% over preinfection levels at virus set-point, whereas animals that progressed rapidly to AIDS had significant loss of mDC at this time. Short term antiretroviral therapy (ART transiently reversed mDC loss in progressor animals, whereas discontinuation of ART resulted in a 3.5-fold increase in mDC over preinfection levels only in stable animals, approaching 10-fold in some cases. Progressive SIV infection was associated with increased CCR7 expression on blood mDC and an 8-fold increase in expression of CCL19 mRNA in lymph nodes, consistent with increased mDC recruitment. Paradoxically, lymph node mDC did not accumulate in progressive infection but rather died from caspase-8-dependent apoptosis that was reduced by ART, indicating that increased recruitment is offset by increased death. Lymph node mDC from both stable and progressor animals remained responsive to exogenous stimulation with a TLR7/8 agonist. These data suggest that mDC are mobilized in SIV infection but that an increase in the CCR7-CCL19 chemokine axis associated with high virus burden in progressive infection promotes exodus of activated mDC from blood into lymph nodes where they die from apoptosis. We suggest that inflamed lymph nodes serve as a sink for mDC through recruitment, activation and death that contributes to AIDS pathogenesis.

  3. Naturally acquired feline immunodeficiency virus (FIV) infection in cats from western Canada: Prevalence, disease associations, and survival analysis


    Ravi, Madhu; Wobeser, Gary A.; Taylor, Susan M.; Jackson, Marion L.


    This retrospective study evaluated epidemiologic features and disease associations of feline immunodeficiency virus (FIV) infection in client owned cats from western Canada. Among 1205 cats that were tested 66 (5.5%) were positive for FIV antibody (FIV+) with a higher prevalence in males than females. FIV+ cats were older than the overall population. Epidemiologic features and disease associations were compared between 58 FIV+, but feline leukemia virus negative (FeLV−) cats and 58 age and se...

  4. TACI mutations and disease susceptibility in patients with common variable immunodeficiency

    NARCIS (Netherlands)

    Poodt, A. E. J.; Driessen, G. J. A.; de Klein, A.; van Dongen, J. J. M.; van der Burg, M.; de Vries, E.

    The most prevalent primary immunodeficiency is common variable immunodeficiency (CVID). Mutations have been described in four genes, ICOS, CD19, BAFF-R and TNFRSF13B (encoding TACI), together associated with 10-15% of CVID cases. We investigated a family with CVID and identified the heterozygous

  5. Improved outcomes on subcutaneous IgG in patients with humoral immunodeficiency and co-morbid bowel disease. (United States)

    Shah, Shaili N; Todoric, Krista; Tarrant, Teresa K


    Immunoglobulin replacement can be life-saving for certain individuals with immunodeficiencies. Subcutaneous IgG (SCIG) is an increasingly used method of replacement over intravenous IgG (IVIG), with potential advantages including fewer systemic side effects, no need for IV access, patient-reported improved quality of life, and decreased cost. However, while patients with certain associated co-morbidities, such as protein-losing enteropathy, may demonstrate more stable IgG levels when on SCIG compared to IVIG, the clinical significance of these experiences is not well described. Using retrospective chart review, we examined three cases in which SCIG and IVIG was administered to patients with either common variable immunodeficiency (CVID) or secondary humoral immunodeficiency and protein-losing gastrointestinal co-morbid disease. Both outpatient and inpatient records were reviewed for data regarding treatment with IVIG versus SCIG, reported frequency and severity of infections, hospitalizations, and IgG levels. All three patients demonstrated improvement in infection rate, stability of IgG levels, and co-morbid disease when on SCIG as compared to IVIG. These findings suggest that the pharmacokinetics of SCIG may translate into more consistent serum IgG levels, contributing to clinical improvement in immunodeficient patients with protein-losing comorbidities when compared to IVIG. Limitations to this study are small patient numbers, retrospective design, and potential therapeutic bias. Further characterization of the effects of co-morbid conditions on immunoglobulin replacement is critical to providing improved and informed patient care.

  6. Novel Mutation of ZAP-70-related Combined Immunodeficiency: First Case from the National Iranian Registry and Review of the Literature. (United States)

    Shirkani, Afshin; Shahrooei, Mohammad; Azizi, Gholamreza; Rokni-Zadeh, Hassan; Abolhassani, Hassan; Farrokhi, Shokrollah; Frans, Glynis; Bossuyt, Xavier; Aghamohammadi, Asghar


    ZAP-70 deficiency is a rare autosomal recessive form of combined immunodeficiency (CID) characterized by selective absence of circulating CD8 T cells with low, normal, or increased CD4 T cells in peripheral blood. Up to now, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID. We present a 3-year-old boy with a history of recurrent bacterial infections and autoimmunity. Initial laboratory findings showed a normal total lymphocyte count, but low levels of CD8 and CD4 T cells and an abnormal lymphocyte proliferation response. Immunoglobulin levels were normal, but the specific antibody response was impaired. Whole exome sequencing revealed a mutation within the kinase domain of ZAP-70. ZAP-70 deficiency should be considered in infants and young children with recurrent bacterial infections, in spite of having palpable lymph nodes, a notable thymus shadow, and a normal total lymphocyte count.

  7. Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    B.E. Strauss


    Full Text Available A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.

  8. Control of equine infectious anemia virus replication following immune reconstitution in an Arabian foal with severe combined immunodeficiency (United States)

    Mealey, Robert H.; Fraser, Darrilyn G.; Oaks, J. Lindsay; Cantor, Glenn H.; McGuire, Travis C.


    Acute infection with equine infectious anemia virus (EIAV), a lentivirus of horses, results in a persistent high-level viremia in Arabian foals affected with severe combined immunodeficiency (SCID). This observation argues against the idea that the transient nature of acute lentiviral viremia is solely a function of viral population dynamics. To extend these studies, EIAV-specific immune reconstitution was attempted prior to EIAV challenge in 2 SCID foals, using adoptively transferred virus-stimulated lymphocytes derived from persistently EIAV-infected half sibling donors. Following transfer, lymphocyte engraftment occurred in 1 foal, and EIAV-specific cytotoxic T lymphocytes as well as neutralizing antibody activity developed. Following a brief period of plasma viremia in this foal, EIAV replication was controlled and plasma virus could not be detected by RT-PCR or culture. These results provide further direct evidence that a specific immune response is required for termination of plasma viremia in acute lentiviral infections. PMID:11683583

  9. Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort. (United States)

    Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon


    The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in

  10. [Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients]. (United States)

    Martínez, Esteban; Jódar Gimeno, Esteban; Reyes García, Rebeca; Carpintero, Pedro; Casado, José Luis; Del Pino Montes, Javier; Domingo Pedrol, Pere; Estrada, Vicente; Maalouf, Jorge; Negredo, Eugenia; Ocampo, Antonio; Muñoz-Torres, Manuel


    To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Correction of murine rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene

    NARCIS (Netherlands)

    N.P. van Til (Niek); H. de Boer (Helen); N. Mashamba (Nomusa); A. Wabik (Agnieszka); M.W. Huston (Marshall W.); T.P. Visser (Trudi); R.J. Fontana (Robert); P.L. Poliani (Pietro); B. Cassani (Barbara); F. Zhang (Fang); A.J. Thrasher (Adrian); A. Anna (Villa); G. Wagemaker (Gerard)


    textabstractRecombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We

  12. Combination antiretroviral therapy and cell–cell spread of wild-type and drug-resistant human immunodeficiency virus-1 (United States)

    Titanji, Boghuma Kabisen; Pillay, Deenan


    Human immunodeficiency virus-1 (HIV-1) disseminates between T cells either by cell-free infection or by highly efficient direct cell–cell spread. The high local multiplicity that characterizes cell–cell infection causes variability in the effectiveness of antiretroviral drugs applied as single agents. Whereas protease inhibitors (PIs) are effective inhibitors of HIV-1 cell–cell and cell-free infection, some reverse transcriptase inhibitors (RTIs) show reduced potency; however, antiretrovirals are not administered as single agents and are used clinically as combination antiretroviral therapy (cART). Here we explored the efficacy of PI- and RTI-based cART against cell–cell spread of wild-type and drug-resistant HIV-1 strains. Using a quantitative assay to measure cell–cell spread of HIV-1 between T cells, we evaluated the efficacy of different clinically relevant drug combinations. We show that combining PIs and RTIs improves the potency of inhibition of HIV-1 and effectively blocks both cell-free and cell–cell spread. Combining drugs that alone are poor inhibitors of cell–cell spread markedly improves HIV-1 inhibition, demonstrating that clinically relevant combinations of ART can inhibit this mode of HIV-1 spread. Furthermore, comparison of wild-type and drug-resistant viruses reveals that PI- and RTI-resistant viruses have a replicative advantage over wild-type virus when spreading by cell–cell means in the presence of cART, suggesting that in the context of inadequate drug combinations or drug resistance, cell–cell spread could potentially allow for ongoing viral replication. PMID:28141491

  13. Combination antiretroviral therapy and cell-cell spread of wild-type and drug-resistant human immunodeficiency virus-1. (United States)

    Titanji, Boghuma Kabisen; Pillay, Deenan; Jolly, Clare


    Human immunodeficiency virus-1 (HIV-1) disseminates between T cells either by cell-free infection or by highly efficient direct cell-cell spread. The high local multiplicity that characterizes cell-cell infection causes variability in the effectiveness of antiretroviral drugs applied as single agents. Whereas protease inhibitors (PIs) are effective inhibitors of HIV-1 cell-cell and cell-free infection, some reverse transcriptase inhibitors (RTIs) show reduced potency; however, antiretrovirals are not administered as single agents and are used clinically as combination antiretroviral therapy (cART). Here we explored the efficacy of PI- and RTI-based cART against cell-cell spread of wild-type and drug-resistant HIV-1 strains. Using a quantitative assay to measure cell-cell spread of HIV-1 between T cells, we evaluated the efficacy of different clinically relevant drug combinations. We show that combining PIs and RTIs improves the potency of inhibition of HIV-1 and effectively blocks both cell-free and cell-cell spread. Combining drugs that alone are poor inhibitors of cell-cell spread markedly improves HIV-1 inhibition, demonstrating that clinically relevant combinations of ART can inhibit this mode of HIV-1 spread. Furthermore, comparison of wild-type and drug-resistant viruses reveals that PI- and RTI-resistant viruses have a replicative advantage over wild-type virus when spreading by cell-cell means in the presence of cART, suggesting that in the context of inadequate drug combinations or drug resistance, cell-cell spread could potentially allow for ongoing viral replication.

  14. Weighted brain networks in disease: centrality and entropy in human immunodeficiency virus and aging. (United States)

    Thomas, Jewell B; Brier, Matthew R; Ortega, Mario; Benzinger, Tammie L; Ances, Beau M


    Graph theory models can produce simple, biologically informative metrics of the topology of resting-state functional connectivity (FC) networks. However, typical graph theory approaches model FC relationships between regions (nodes) as unweighted edges, complicating their interpretability in studies of disease or aging. We extended existing techniques and constructed fully connected weighted graphs for groups of age-matched human immunodeficiency virus (HIV) positive (n = 67) and HIV negative (n = 77) individuals. We compared test-retest reliability of weighted versus unweighted metrics in an independent study of healthy individuals (n = 22) and found weighted measures to be more stable. We quantified 2 measures of node centrality (closeness centrality and eigenvector centrality) to capture the relative importance of individual nodes. We also quantified 1 measure of graph entropy (diversity) to measure the variability in connection strength (edge weights) at each node. HIV was primarily associated with differences in measures of centrality, and age was primarily associated with differences in diversity. HIV and age were associated with divergent measures when evaluated at the whole graph level, within individual functional networks, and at the level of individual nodes. Graph models may allow us to distinguish previously indistinguishable effects related to HIV and age on FC. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The association between parental consanguinity and primary immunodeficiency diseases: A systematic review and meta-analysis. (United States)

    Hadizadeh, Hasti; Salehi, Masoud; Khoramnejad, Shabnam; Vosoughi, Kia; Rezaei, Nima


    We aimed to establish the prevalence of parental consanguinity among patients with primary immunodeficiency diseases (PID) and compare the prevalence with the general population. We searched PubMed, EMBASE, and Scopus for studies mentioning parental consanguinity prevalence in patients with PID and calculated the prevalence odds ratio (POR) of parental consanguinity in each study, compared to a matched healthy population. We identified 21 eligible studies with a total population of 18091 accounting for sample overlap. The POR among studies on a sample of mixed patients with PID ranged from 0.6 to 21.9 with the pooled POR of 3.0 (p consanguinity compared to the healthy population, a phenomenon not observed in other inheritance patterns. Determining the extent of the impact that consanguinity imposes upon the progeny paves the way for convincing healthcare policymakers in highly consanguineous communities to act more diligently in informing the masses about the consequences of practicing inbreeding. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Promoting Cardiovascular Health in Patients Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome. (United States)

    Harris, Robin


    Patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (PLWHA) are at increased risk of cardiovascular disease because of advances in human immunodeficiency virus/acquired immunodeficiency syndrome treatment and increased life expectancy. Cardiovascular health promotion in PLWHA includes strategies for risk factor reduction, disease prevention, early detection, and treatment of cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. [Interferon-alpha and ribavirin combination therapy for co-infection of hepatitis C virus and human immunodeficiency virus]. (United States)

    Zheng, Yu-huang; He, Yan; Yang, Xu; Gong, Guo-zhong; Zhou, Hua-ying; Zhang, Chun-ying; Zhou, Wen; Huang, Li; Ding, Pei-pei; Li, Hui


    To evaluate the clinical effect and side-effect of interferon-alpha (IFN-a) and ribavirin (RBV) combination therapy for Chinese patients with co-infection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and to compare them with only HIV infection patients. 10 patients with HCV-HIV and 17 patients with only HCV infection received 5 million units of IFNalpha-2b every other day intramuscularly, and 300 mg RBV orally three times a day. Dynamic observations were done for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measures, and the side-effects of the medicines. After 12 weeks and 24 weeks of IFNalpha and RBV combination therapy, mean HCV RNA levels reduced 1.14 log (t = 3.843, P HIV co-infection group, and reduced 1.48 log (t = 6.438, P less than 0.01) and 2.33 log (t = 7.343, P HIV RNA levels decreased 1.22 log (t = 3.662, P HIV and HCV patients at week 0, week 12 and week 24. All 27 patients showed satisfactory biochemical response to therapy. There were some mild or moderate influenza-like symptoms, intestinal discomfort and decreased blood cell counts in the early stages of the treatments. No neuropsychic and auto-immune disorders were found. IFNalpha-2b and RBV combination therapy showed similar anti-HCV effects during the 24 week treatment for HCV-HIV and HCV infected patients, and some anti-HIV effect was also observed. No obvious different biochemical responses and side-effects were found between the above two groups.

  18. T Cell Lymphoma and Leukemia in Severe Combined Immunodeficiency Pigs following Bone Marrow Transplantation: A Case Report

    Directory of Open Access Journals (Sweden)

    Ellis J. Powell


    Full Text Available After the discovery of naturally occurring severe combined immunodeficiency (SCID within a selection line of pigs at Iowa State University, we found two causative mutations in the Artemis gene: haplotype 12 (ART12 and haplotype 16 (ART16. Bone marrow transplants (BMTs were performed to create genetically SCID and phenotypically immunocompetent breeding animals to establish a SCID colony for further characterization and research utilization. Of nine original BMT transfer recipients, only four achieved successful engraftment. At approximately 11 months of age, both animals homozygous for the ART16 mutation were diagnosed with T cell lymphoma. One of these ART16/ART16 recipients was a male who received a transplant from a female sibling; the tumors in this recipient consist primarily of Y chromosome-positive cells. The other ART16/ART16 animal also presented with leukemia in addition to T cell lymphoma, while one of the ART12/ART16 compound heterozygote recipients presented with a nephroblastoma at a similar age. Human Artemis SCID patients have reported cases of lymphoma associated with a “leaky” Artemis phenotype. The naturally occurring Artemis SCID pig offers a large animal model more similar to human SCID patients and may offer a naturally occurring cancer model and provides a valuable platform for therapy development.

  19. Two mutational hotspots in the interleukin-2 receptor {gamma} chain gene causing human X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Institutes of Health, Bethesda, MD (United States); Buckley, R.H. [and others


    Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor {gamma} chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. 41 refs., 5 figs., 1 tab.

  20. Nonrandom X chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Wengler, G.S.; Parolini, O.; Conley, M.E. (Univ. of Tennessee, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Allen, R.C. (Baylor College of Medicine, Houston, TX (United States)); Smith, H. (St. Jude Children' s Research Hospital, Memphis, TN (United States))


    X-linked severe combined immunodeficiency (XSCID) is characterized by hypogammaglobulinemia, markedly reduced numbers of T cells, absent mitogen responses, decreased numbers of NK cells, and normal or elevated numbers of B cells. The abnormalities in the NK cell and B cell lineages could be attributed to dependence of these cell lineages on T cells or T cell-derived factors, or to expression of the XSCID gene defect in these cell lineages. In past experiments, the authors have examined X chromosome inactivation patterns in T cells and cultured B cells from female obligate carriers of XSCID and have found that both cell lineages demonstrate nonrandom X chromosome inactivation. This indicates that the gene defect is intrinsic to both of these cell lineages. In the present experiments, a polymerase chain reaction technique was used to evaluate X chromosome inactivation patterns in highly purified populations of freshly isolated NK cells, B cells, CD4[sup +] cells, and CD8[sup +] cells from three obligate carriers of XSCID. All four lymphoid cell populations from these three women exhibited exclusive use of a single X as the active X. In contrast, both X chromosomes were used as the active X in neutrophils and monocytes. These findings indicate that the XSCID gene is expressed in the NK cell lineage as well as in T cells and B cells. This observation makes it highly unlikely that the XSCID gene is involved in Ag receptor gene rearrangements. 21 refs., 4 figs.

  1. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. (United States)

    Malhotra, U; Berrey, M M; Huang, Y; Markee, J; Brown, D J; Ap, S; Musey, L; Schacker, T; Corey, L; McElrath, M J


    T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

  2. RNA silencing and HIV: A hypothesis for the etiology of the severe combined immunodeficiency induced by the virus

    Directory of Open Access Journals (Sweden)

    Ludwig Linda B


    Full Text Available Abstract A novel intrinsic HIV-1 antisense gene was previously described with RNA initiating from the region of an HIV-1 antisense initiator promoter element (HIVaINR. The antisense RNA is exactly complementary to HIV-1 sense RNA and capable of forming ~400 base-pair (bp duplex RNA in the region of the long terminal repeat (LTR spanning the beginning portion of TAR in the repeat (R region and extending through the U3 region. Duplex or double-stranded RNA of several hundred nucleotides in length is a key initiating element of RNA interference (RNAi in several species. This HIVaINR antisense RNA is also capable of forming multiple stem-loop or hairpin-like secondary structures by M-fold analysis, with at least one that perfectly fits the criteria for a microRNA (miRNA precursor. MicroRNAs (miRNAs interact in a sequence-specific manner with target messenger RNAs (mRNAs to induce either cleavage of the message or impede translation. Human mRNA targets of the predicted HIVaINR antisense RNA (HAA microRNAs include mRNA for the human interleukin-2 receptor gamma chain (IL-2RG, also called the common gamma (γc receptor chain, because it is an integral part of 6 receptors mediating interleukin signalling (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R. Other potential human mRNA targets include interleukin-15 (IL-15 mRNA, the fragile × mental retardation protein (FMRP mRNA, and the IL-1 receptor-associated kinase 1 (IRAK1 mRNA, amongst others. Thus the proposed intrinsic HIVaINR antisense RNA microRNAs (HAAmiRNAs of the human immunodeficiency virus form complementary targets with mRNAs of a key human gene in adaptive immunity, the IL-2Rγc, in which genetic defects are known to cause an X-linked severe combined immunodeficiency syndrome (X-SCID, as well as mRNAs of genes important in innate immunity. A new model of intrinsic RNA silencing induced by the HIVaINR antisense RNA in the absence of Tat is proposed, with elements suggestive of both small

  3. Human immunodeficiency virus and sexually transmitted diseases between the vulnerable populations in Kazakhstan

    Directory of Open Access Journals (Sweden)

    Zh. Z. Trumova


    Full Text Available The human immunodeficiency virus (HIV epidemic continues to expand in Eastern Europe and Central Asia according to UNAIDS data (2012, Geneva. The rate of new HIV infections AIDS – related mortality has increased by 25 % from 2001 to 2009 in Kazakhstan (WHO data, 2012. The number of new HIV infections among newly diagnosed patients attributed to heteroand homosexual contact has been steadily increasing. There is also higher rate of HIV among Injecting Drug Users. There is an increase incidence of co-infections especially sexually transmitted diseases. In fact, comorbid STIs increase patients' susceptibility of acquiring and transmitting HIV (Guenthner PC, Secor WE, Dezzutti CS., 2005; Kissinger P, Amedee A, Clark RA, et al. , 2009. HIV/AIDS shares transmission characteristics with other sexual and blood-borne agents. Higher sexual mixing rates and lack of condom use are conspicuous risk factors (Vermund et al. 2009. However, while all groups are affected by HIV, some are more vulnerable than others: sex workers (SWs, men who have sex with men (MSM, injecting drug users (IDU. All these findings determined to set up the goal of this research. The purpose of the study is еpidemiologic situation of human immunodeficiency virus (HIV/AIDS and related STIs in the Republic of Kazakhstan and in some vulnerable population groups to HIV infection. Materials and methods. To study the dynamics of HIV/STIs in Kazakhstan (cumulatively an analysis of 2012–2013 years statistics was conducted. Testing for HIV/STI of blood samples of the vulnerable groups was carried out in the laboratories of AIDS centers. The algorithm of confirming the diagnosis of HIV infection included a twofold enzyme immunoassay (EIA study of blood samples. Samples with positive results of the first EIA were retested using expert test systems; in case with a positive result of the second EIA a confirmatory test was conducted using a method of HIV-1 Western blot in the reference

  4. Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants. (United States)

    Schoeman, Johannes C; Moutloatse, Gontse P; Harms, Amy C; Vreeken, Rob J; Scherpbier, Henriette J; Van Leeuwen, Liesbeth; Kuijpers, Taco W; Reinecke, Carools J; Berger, Ruud; Hankemeier, Thomas; Bunders, Madeleine J


    Increased morbidity and fetal growth restriction are reported in uninfected children born to human immunodeficiency virus type 1 (HIV-1)-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress, skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART) exposure on the infants' immune metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning. The lipid metabolism was further dysregulated with increased triglyceride species and a subsequent decrease in phospholipids in cART/HIV-1-exposed infants compared to control infants. Proinflammatory immune mediators, lysophospholipids as well as cytokines such as CXCL10 and CCL3, were increased whereas anti-inflammatory metabolites from the cytochrome P450 pathway were reduced in cART/HIV-1-exposed infants. Taken together, these data demonstrate that the fetal metabolism is impacted by maternal factors (cART and HIV-1) and skews physiological immune responses toward inflammation in the newborn infant. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  5. Extraintestinal rotavirus infections in children with immunodeficiency. (United States)

    Gilger, M A; Matson, D O; Conner, M E; Rosenblatt, H M; Finegold, M J; Estes, M K


    Some rotavirus strains, including vaccine candidates, have been demonstrated to cause hepatitis in immunodeficient and malnourished mice and to grow in human liver cells. To determine whether rotavirus spreads outside the intestine in naturally infected children, we examined tissues from four immunodeficient children affected with severe combined immunodeficiency disease, acquired immunodeficiency disease syndrome, or DiGeorge syndrome. Chronic rotavirus-related diarrhea, which persisted until death, had also developed in each child. Using indirect immunoperoxidase techniques, we identified rotavirus antigen in the liver and kidney with a hyperimmune guinea pig antiserum prepared to double-shelled rotavirus particles. Similar immunostaining with an antiserum to a rotavirus nonstructural protein (NS26) provided evidence of active virus replication. The observed reactivity was eliminated specifically when serial sections were immunostained with the same antiserum that had been absorbed with either double-shelled rotavirus particles or NS26. Immunostaining was not observed in the liver of children with other diseases (alpha 1-antitrypsin deficiency, inspissated bile syndrome, and acute rejection of a transplanted liver). These findings demonstrate that rotavirus infections in children can extend beyond the intestinal tract. Further studies are warranted to determine whether extraintestinal rotavirus replication occurs in children without severe immunodeficiency, such as malnourished children.

  6. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults. (United States)

    Scott, Jake; Goetz, Matthew Bidwell


    Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities. Published by Elsevier Inc.

  7. Clinical experience with Flebogamma 5% DIF: a new generation of intravenous immunoglobulins in patients with primary immunodeficiency disease. (United States)

    Ballow, M


    The development of effective, safe, liquid intravenous immunoglobulins (IVIG) preparations has represented a major therapeutic advancement in the treatment of patients with antibody deficiencies. Flebogamma 5% was the first liquid IVIG licensed in Europe that has been widely used in the treatment of immunodeficiency diseases. It has been proven to have an excellent efficacy and safety profile. Flebogamma 5% dual inactivation and filtration (DIF) is a newly developed IVIG preparation that shares formulation characteristics and identical biochemical and stability profiles with Flebogamma 5%. In addition to pasteurization, already performed in Flebogamma 5%, solvent-detergent treatment and sequential nanofiltration through filters with pore sizes of 35 nm followed by 20 nm have been added to further enhance the pathogen safety margin. The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma 5% DIF for immunoglobulin replacement therapy in patients with primary immunodeficiency diseases (PID). Flebogamma 5% DIF was administered at seven clinical sites to 46 subjects with well-defined primary immunodeficiency diseases at a dose of 300-600 mg/kg every 21-28 days for 12 months. The serious bacterial infection rate was 0.021/subject/year. The incidence of adverse events considered potentially related to Flebogamma 5% DIF during or within 72 h after completing an infusion was approximately 10%. The half-life in serum of the administered IgG was around 31 days. In summary, Flebogamma 5% DIF is efficacious and safe, has good pharmacokinetic properties, is well-tolerated and maintains the profile of Flebogamma 5% for the treatment of patients with primary humoral immune deficiency diseases.

  8. Biallelic modification of IL2RG leads to severe combined immunodeficiency in pigs

    Directory of Open Access Journals (Sweden)

    Jung-Taek Kang


    Full Text Available Abstracts Background Pigs with SCID can be a useful model in regenerative medicine, xenotransplantation, and cancer cell transplantation studies. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, we report generation and phenotypic characterization of IL2RG knockout female pigs produced through combination of CRISPR/Cas9 system and SCNT. As expected, pigs lacking IL2RG presented SCID phenotype. Methods First, specific CRISPR/Cas9 systems targeting IL2RG were introduced into developing pig embryos then the embryos were transferred into surrogates. A total of six fetuses were obtained from the embryo transfer and fetal fibroblast cell lines were established. Then IL2RG knockout female cells carrying biallelic genetic modification were used as donor cells for SCNT, followed by embryo transfer. Results Three live cloned female piglets carrying biallelic mutations in IL2RG were produced. All cloned piglets completely lacked thymus and they had a significantly reduced level of mature T, B and NK cells in their blood and spleen. Conclusions Here, we generated IL2RG knockout female pigs showing phenotypic characterization of SCID. This IL2RG knockout female pigs will be a promising model for biomedical and translational research.

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

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    Turkan Patiroglu


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

  10. Economic evaluation of Safer Choices: a school-based human immunodeficiency virus, other sexually transmitted diseases, and pregnancy prevention program. (United States)

    Wang, L Y; Davis, M; Robin, L; Collins, J; Coyle, K; Baumler, E


    To evaluate the cost-effectiveness and cost benefit of Safer Choices, a school-based human immunodeficiency virus, other sexually transmitted diseases, and unintended pregnancy prevention intervention for high school students. The baseline cost-effectiveness and cost benefit were derived in 4 steps: (1) estimation of intervention costs; (2) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted, and development of a model to translate increases in contraceptive use into cases of pregnancy averted; (3) translation of cases averted into medical costs and social costs averted; and (4) calculation of the net benefit of the program. Multivariable sensitivity analysis was performed to determine the robustness of the base-case results. Under base-case assumptions, at an intervention cost of $105,243, Safer Choices achieved a 15% increase in condom use and an 11% increase in contraceptive use within 1 year among 345 sexually active students. An estimated 0.12 cases of human immunodeficiency virus, 24.37 cases of chlamydia, 2.77 cases of gonorrhea, 5.86 cases of pelvic inflammatory disease, and 18.5 pregnancies were prevented. For every dollar invested in the program, $2.65 in total medical and social costs were saved. Results of most of the scenarios remained cost saving under a wide range of model variable estimates. The Safer Choices program is cost-effective and cost saving in most scenarios considered. School-based prevention programs of this type warrant careful consideration by policy makers and program planners. Program cost data should be routinely collected in evaluations of adolescent prevention programs.

  11. Naturally acquired feline immunodeficiency virus (FIV) infection in cats from western Canada: Prevalence, disease associations, and survival analysis. (United States)

    Ravi, Madhu; Wobeser, Gary A; Taylor, Susan M; Jackson, Marion L


    This retrospective study evaluated epidemiologic features and disease associations of feline immunodeficiency virus (FIV) infection in client owned cats from western Canada. Among 1205 cats that were tested 66 (5.5%) were positive for FIV antibody (FIV(+)) with a higher prevalence in males than females. FIV(+) cats were older than the overall population. Epidemiologic features and disease associations were compared between 58 FIV(+), but feline leukemia virus negative (FeLV(-)) cats and 58 age and sex matched FIV-negative (FIV(-)), FeLV(-) cats. FIV positivity was associated with a history of bite wounds, increasing age, and male gender. Lethargy and oral diseases were significantly associated with FIV positivity. Although several FIV(+) cats were euthanized, the survival time of FIV(+) cats after diagnosis was not significantly different from that of FIV(-) cats. In summary, FIV prevalence was low in cats from western Canada, clinical signs/diseases were mild, and lifespan was not different in FIV(+) cats.

  12. Nonrandon X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Conley, M.E.; Lavoie, A.; Briggs, C.; Brown, P.; Guerra, C.; Puck, J.M.


    X chromosome-linked sever combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated number of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, the authors analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosome, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation.

  13. The carrier prevalence of severe combined immunodeficiency, lavender foal syndrome and cerebellar abiotrophy in Arabian horses in South Africa. (United States)

    Tarr, C J; Thompson, P N; Guthrie, A J; Harper, C K


    The carrier prevalence of severe combined immunodeficiency (SCID), lavender foal syndrome (LFS) and cerebellar abiotrophy (CA) in Arabian foals in South Africa was determined in order to quantify the potential impact of these conditions locally. Furthermore, the carrier prevalence of SCID prior to and following the introduction of a genetic test was compared to evaluate the effect of testing in the population. To estimate the carrier prevalence of SCID, LFS and CA in registered purebred Arabians born in South Africa in the 2004/5 and 2009/10 foaling seasons and compare the changes in prevalence in these disorders between the 2 groups of foals. Cross-sectional survey. Samples were collected from individuals randomly selected from 2 populations of purebred Arabian foals born during the 2004/5 and 2009/10 foaling seasons. Genetic testing for SCID, LFS and CA was performed on DNA extracts using specific polymerase chain reactions, with the products being analysed using fragment analysis on a genetic analyser. The carrier prevalence of LFS and CA for the 2009/10 season was 11.7% (95% confidence interval [CI] 7.6-17.0%) and 5.1% (95% CI 2.5-9.1%), respectively, with no statistically significant change in prevalence between the 2004/5 and 2009/10 foaling seasons. However, the carrier prevalence of SCID was found to have decreased significantly from 6.4% (95% CI 4.8-8.3%) in the 2004/5 foals to 3.4% (95% CI 2.2-5.1%) in the 2009/10 foals (P = 0.009). The results of this study indicate that genetic screening of Arabian horses for SCID may have played a role in significantly reducing the carrier prevalence within the breeding population and thereby reducing the birth of clinically affected individuals. This study provides an indication of the positive effect of genetic screening for specific conditions in horses. © 2013 EVJ Ltd.

  14. Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray (United States)

    Bayer, D K; Martinez, C A; Sorte, H S; Forbes, L R; Demmler-Harrison, G J; Hanson, I C; Pearson, N M; Noroski, L M; Zaki, S R; Bellini, W J; Leduc, M S; Yang, Y; Eng, C M; Patel, A; Rodningen, O K; Muzny, D M; Gibbs, R A; Campbell, I M; Shaw, C A; Baker, M W; Zhang, V; Lupski, J R; Orange, J S; Seeborg, F O; Stray-Pedersen, A


    In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8+ T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20–30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5–10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients. PMID:25046553

  15. Novel ZBTB24 Mutation Associated with Immunodeficiency, Centromere Instability, and Facial Anomalies Type-2 Syndrome Identified in a Patient with Very Early Onset Inflammatory Bowel Disease. (United States)

    Conrad, Máire A; Dawany, Noor; Sullivan, Kathleen E; Devoto, Marcella; Kelsen, Judith R


    Very early onset inflammatory bowel disease, diagnosed in children ≤5 years old, can be the initial presentation of some primary immunodeficiencies. In this study, we describe a 17-month-old boy with recurrent infections, growth failure, facial anomalies, and inflammatory bowel disease. Immune evaluation, whole-exome sequencing, karyotyping, and methylation array were performed to evaluate the child's constellation of symptoms and examination findings. Whole-exome sequencing revealed that the child was homozygous for a novel variant in ZBTB24, the gene associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome. This describes the first case of inflammatory bowel disease associated with immunodeficiency, centromere instability, and facial anomalies type-2 syndrome in a child with a novel disease-causing mutation in ZBTB24 found on whole-exome sequencing.

  16. Severe Combined Immunodeficiency (SCID) (United States)

    ... and her daughter Every patient — from coping to hoping. Every donor or volunteer — from altruism to inspiration. ... this type of SCID have very few working white blood cells to fight infection. Only boys can ...

  17. Severe Combined Immunodeficiency (SCID) (United States)

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  18. Severe Combined Immunodeficiency (SCID) (United States)

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  19. Flebogamma(®) 5 % DIF Intravenous Immunoglobulin for Replacement Therapy in Children with Primary Immunodeficiency Diseases. (United States)

    Ballow, Mark; Pinciaro, Paul J; Craig, Timothy; Kleiner, Gary; Moy, James; Ochs, Hans D; Sleasman, John; Smits, William


    The previous studies with Flebogamma(®) 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5 % DIF for replacement therapy in children (age 2-16) with primary immunodeficiency diseases (PIDD). IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300-800 mg/kg every 21-28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels. The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations. Flebogamma(®) 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma(®) 5 % for the treatment of children with primary humoral immunodeficiency diseases.

  20. Chlamydia trachomatis in human immunodeficiency virus-infected men treated at a referral hospital for sexually transmitted diseases in the Amazonas, Brazil. (United States)

    Jalkh, Alex Panizza; Miranda, Angelica Espinosa; Hurtado-Guerreiro, Jose Camilo; Ramos, Lorena Angelica Castano; Figliuolo, Guiseppe; Maia, Jussimara; Costa, Cintia Mara; Ramasawmy, Rajendranath; de Lima Ferreira, Luiz Carlos


    The aim of the present study was to determine the Chlamydia trachomatis prevalence and to identify the demographic, behavioural and clinical factors associated with C. trachomatis in human immunodeficiency virus infected men. This was a cross-sectional study of C. trachomatis prevalence among human immunodeficiency virus-infected men enrolled at the Outpatient clinic of acquired immunodeficiency syndrome of the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil. C. trachomatis deoxyribonucleic acid from urethral samples was purified and submitted to real time polymerase chain reaction to identify the presence of C. trachomatis. A total of 276 human immunodeficiency virus-infected men were included in the study. The prevalence of C. trachomatis infection was 12% (95% confidence interval 8.1%-15.7%). The mean age of the participants was 34.63 (standard deviation 10.80) years. Of the 276 human immunodeficiency virus-infected men, 93 (56.2%) had more than one sexual partner in the past year and 105 (38.0%) reported having their first sexual intercourse under the age of 15 years. Men having sex with men and bisexuals amounted to 61.2% of the studied population. A total of 71.7% had received human immunodeficiency virus diagnosis in the last three years and 55.1% were using antiretroviral therapy. Factors associated with C. trachomatis infection in the logistic model were being single (p<0.034), men having sex with men (p<0.021), and having previous sexually transmitted diseases (p<0.001). The high prevalence of C. trachomatis infection among human immunodeficiency virus-infected men highlights that screening human immunodeficiency virus-infected men for C. trachomatis, especially among men having sex with men, is paramount to control the spread of C. trachomatis infection. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  1. The skin in primary immunodeficiency disorders

    NARCIS (Netherlands)

    Sillevis Smitt, J. Henk; Wulffraat, Nico M.; Kuijpers, Taco W.


    Primary immunodeficiency disorders comprise serious and rare diseases, predominantly in children. The skin may be involved in a primary immunodeficiency and the cutaneous alterations such as infections, eczematous dermatitis, erythroderma, autoimmune dermatoses and vasculitis may be the basis for

  2. Summary of the Centers for Disease Control human immunodeficiency virus (HIV) performance evaluation surveys for 1985 and 1986. (United States)

    Taylor, R N; Przybyszewski, V A


    During 1985 and 1986, the Centers for Disease Control conducted eight surveys to evaluate laboratory performance in testing for antibody to human immunodeficiency virus (HIV). (Other names for this virus include "human T-lymphotropic virus type III" and "lymphadenopathy associated virus.") The first survey was conducted with ten samples and 50 laboratories; the remaining surveys used six samples, but enrollment increased to as many as 475 laboratories. The purpose of these surveys was to measure test performance by the laboratories under the actual conditions of use. The surveys contained duplicate samples to permit measurement of within- and between-survey reproducibility. One survey included positive and negative reference materials as evaluation samples. Results of the Western blot (WB) test were not always positive on samples that were positive by enzyme immunoassay (EIA), and sometimes they were positive on samples that had negative results by EIA. The percentage of positive results reported by laboratories using Electronucleonics tests was lower than that reported by users of Abbott and of Litton tests. positive results on the negative reference material were reported by 13.7% of the Abbott EIA test users. The tests do not seem to be calibrated against an equivalent standard. Within-survey reproducibility was usually above 95% for EIA and WB methods and for the major manufacturers of EIA tests. Between-survey reproducibility was usually above 90%. Reproducibility was below 75% for some combinations of samples, method, and manufacturer. The test performance observed in these surveys may be lower than is actually achieved on patient samples because the samples were selected to measure technical competence and contain a higher frequency of samples with low reactivity than would be encountered with clinical samples. Stratification and weighting of the results in these surveys to estimate performance parameters for a blood bank population indicate that the tests

  3. [Diseases of the peripheral and visual nervous system during infection with human immunodeficiency virus]. (United States)

    Casanova-Sotolongo, P; Casanova-Carrillo, P; Casanova-Carrillo, C

    Infection with human immunodeficiency virus (HIV) is often accompanied by neurological complications. One of these includes disorders affecting the peripheral and visual nervous system, especially during the acquired immunodeficiency syndrome (AIDS) stage. The peripheral neuropathies associated with infection by HIV are an assorted group of disorders, which include acute or chronic inflammatory demyelinating polyneuropathy, multiple mononeuropathy and neuropathies related to the herpes zoster virus or cytomegalovirus. The most common and clinically important of the neuropathies is painful distal sensory polyneuropathy (DSP). The most severely affected cranial nerves are V and VII. The isolation of HIV from the affected nerves suggests a direct role, but an immune mechanism is also possible. Although cytomegalovirus may be associated with a variety of peripheral nerve syndromes, its clinical presentation as a primary demyelinating polyneuropathy is unusual. DSP and antiretroviral toxic neuropathy are the most common HIV-associated neuropathies. Both HIV infection, by itself, and the neurotoxicity of certain drugs in tritherapy contribute to the development of painful peripheral sensory neuropathy. In researching into the cause of HIV-associated neuropathy further studies are needed to determine the relative roles played by the viral infection and the activation of the immunological factors that contribute to the pathogenesis of the damage done in axons, the dorsal root ganglion and in the sensory pathways in the spinal cord.

  4. Cancers related to Immunodeficiencies:Update and perspectives

    Directory of Open Access Journals (Sweden)

    Esmaeil Mortaz


    Full Text Available The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. Whilst, the incidence of primary immunodeficiencies (PIDs is 1:10.000 births, that of secondary immunodeficiencies is more common and are associated with post transplantation immune dysfunction or with immunosuppressive medication for human immunodeficiency virus (HIV or with human T-cell lymphotropic virus (HTLV infection.After infection, malignancy is the most prevalent cause of death in both children and adults with primary immunodeficiency disorders (PIDs. PIDs more often associated with cancer include common variable immunodeficiency (CVID, Wiskott Aldrich syndrome (WAS, ataxia-telangiectasia (AT and severe combined immunodeficiency (SCID. This suggests that a protective immune response against both infectious non-self (pathogens and malignant self-challenges (cancer exist. The increased incidence of cancer has been attributed to defective elimination of altered or transformed cells and/or defective immunity towards cancer cells. The concept of abberant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies, the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.

  5. Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: a rare fatal complication. (United States)

    Eyre, Toby A; Pelosi, Emanuela; McQuaid, Stephen; Richardson, Deborah; Newman, Joan; Hill, Kate; Veys, Paul; Davies, Graham; Orchard, Kim H


    We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Chronic granulomatous disease: a 25-year patient registry based on a multistep diagnostic procedure, from the referral center for primary immunodeficiencies in Greece

    NARCIS (Netherlands)

    Raptaki, Maria; Varela, Ioanna; Spanou, Kleopatra; Tzanoudaki, Marianna; Tantou, Sofia; Liatsis, Manolis; Constantinidou, Nikki; Bakoula, Chryssa; Roos, Dirk; Kanariou, Maria


    Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency caused by the absence or dysfunction of one of NADPH oxidase subunits, with heterogeneous genetic aetiologies. The aim of this study was the CGD patient registry in Greece, the identification of the responsible genotype and

  7. The Influence of Pregnancy, Sexually Transmitted Diseases, and Human Immunodeficiency Virus Perceived Susceptibility Patterns on Sexual Risk Reduction for Adolescent Females (United States)

    Kershaw, Trace S.; Ethier, Kathleen A.; Milan, Stephanie; Lewis, Jessica B.; Niccolai, Linda M.; Meade, Christina; Ickovics, Jeannette R.


    Risky sexual behavior can lead to pregnancy, sexually transmitted diseases (STDs), and human immunodeficiency virus (HIV). Our study of 300 adolescent females takes an integrative approach by incorporating these multiple outcomes to assess the influence of risk perceptions on sexual behavior by (1) identifying subgroups of perceived susceptibility…

  8. [Combined operation for ischemic heart diseases and valvular heart diseases]. (United States)

    Inoue, M; Ohba, O; Shichijo, T; Yunoki, K; Suezawa, T; Honjo, O; Kyo, Y


    We performed combined operation for patients who have both ischemic heart disease and valvular heart disease in 21 cases from January 1991 to October 1999. This operation was 3.1% of 682 cases of coronary artery bypass grafting and 5.0% of 416 cases of operation for valvular heart disease during that period. The mean age of these patients was 67.9 +/- 9.1 years. The average number of grafts in the coronary artery bypass grafting was 1.5 +/- 0.6. Aortic valve replacement was performed in 6 cases, mitral valve replacement in 10 cases and mitral valve plasty in 5 cases. Together with this combined operation, ascending aorta and aortic arch replacement was done in 1 case and abdominal aortic replacement in 2 cases. Three patients died due to postoperative aortic rupture, cerebral infarction or excessive surgical intervention in ascending aorta and aortic arch replacement. Combined operation for ischemic heart diseases and valvular heart diseases can safely performed, but it appears necessary to pay attention to arteriosclerotic lesions.

  9. [Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. (United States)

    Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M


    The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID using zinc-finger nucleases.

    Directory of Open Access Journals (Sweden)

    Tomoji Mashimo

    Full Text Available BACKGROUND: Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. METHODOLOGY/PRINCIPAL FINDINGS: We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID. Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. CONCLUSIONS AND SIGNIFICANCE: The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.

  11. Keratinocyte antiviral response to Poly(dA:dT stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency.

    Directory of Open Access Journals (Sweden)

    Jennifer A Luff

    Full Text Available X-linked severe combined immunodeficiency (XSCID is caused by a genetic mutation within the common gamma chain (γc, an essential component of the cytokine receptors for interleukin (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are most commonly treated with bone marrow transplants (BMT to restore systemic immune function. However, BMT-XSCID humans and dogs remain at an increased risk for development of cutaneous papillomavirus (PV infections and their associated neoplasms, most typically cutaneous papillomas. Since basal keratinocytes are the target cell for the initial PV infection, we wanted to determine if canine XSCID keratinocytes have a diminished antiviral cytokine response to poly(dA:dT and canine papillomavirus-2 (CPV-2 upon initial infection. We performed quantitative RT-PCR for antiviral cytokines and downstream interferon stimulated genes (ISG on poly(dA:dT stimulated and CPV-2 infected monolayer keratinocyte cultures derived from XSCID and normal control dogs. We found that XSCID keratinocytes responded similarly to poly(dA:dT as normal keratinocytes by upregulating antiviral cytokines and ISGs. CPV-2 infection of both XSCID and normal keratinocytes did not result in upregulation of antiviral cytokines or ISGs at 2, 4, or 6 days post infection. These data suggest that the antiviral response to initial PV infection of basal keratinocytes is similar between XSCID and normal patients, and is not the likely source for the remaining immunodeficiency in XSCID patients.

  12. Imaging combined autoimmune and infectious disease microarrays (United States)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark


    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  13. Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques (United States)

    Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.


    Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

  14. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells. (United States)

    Kuijpers, Taco W; van Leeuwen, Ester M M; Barendregt, Barbara H; Klarenbeek, Paul; aan de Kerk, Daan J; Baars, Paul A; Jansen, Machiel H; de Vries, Niek; van Lier, René A W; van der Burg, Mirjam


    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.

  15. Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function. (United States)

    Underwood, Jonathan; Cole, James H; Caan, Matthan; De Francesco, Davide; Leech, Robert; van Zoest, Rosan A; Su, Tanja; Geurtsen, Gert J; Schmand, Ben A; Portegies, Peter; Prins, Maria; Wit, Ferdinand W N M; Sabin, Caroline A; Majoie, Charles; Reiss, Peter; Winston, Alan; Sharp, David J


    Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort. Cognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion, and volumetric data, taking advantage of the complementary information they provide. Compared to the highly comparable control group, cognitive function was impaired in 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the gray matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV infection, and systemic immune activation. Cognitive impairment, lower gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals.

  16. Primary immunodeficiency in combination with transverse upper limb defect and anal atresia in a 34-year-old patient with Jacobsen syndrome. (United States)

    von Bubnoff, Dagmar; Kreiss-Nachtsheim, Martina; Novak, Natalija; Engels, Eva; Engels, Hartmut; Behrend, Claudia; Propping, Peter; de la Salle, Henri; Bieber, Thomas


    We describe a 34-year-old male patient with Jacobsen syndrome associated with a broad spectrum of anomalies and an increased susceptibility to infections. Features commonly seen in Jacobsen syndrome were short stature, mental retardation, congenital heart disease, cryptorchidism, strabismus, distal hypospadia glandis, and mild thrombocytopenia. Chromosome analysis disclosed a mosaic 46,XY,del(11)(q24.1)/46,XY karyotype with a very low percentage of normal cells. In addition, transverse upper limb defect, imperforate anus, and hearing impairment were noted. Cellular anomalies include functional impairment and deficiency of T-helper cells, and a low serum immunoglobulin M (IgM)-level. The presence of a transverse limb defect and primary immunodeficiency has not been reported previously in Jacobsen syndrome. Copyright 2003 Wiley-Liss, Inc.

  17. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter


    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  18. Human Immunodeficiency Virus-Associated Gastrointestinal Disease: Common Endoscopic Biopsy Diagnoses

    Directory of Open Access Journals (Sweden)

    Feriyl Bhaijee


    Full Text Available The gastrointestinal (GI tract is a major site of disease in HIV infection: almost half of HIV-infected patients present with GI symptoms, and almost all patients develop GI complications. GI symptoms such as anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea are frequent and usually nonspecific among these patients. Endoscopy is the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic and histopathologic evaluation can render diagnoses in patients with non-specific symptoms. In the past three decades, studies have elucidated a variety of HIV-associated inflammatory, infectious, and neoplastic GI diseases, often with specific predilection for various sites. HIV-associated esophageal disease, for example, commonly includes candidiasis, cytomegalovirus (CMV and herpes simplex virus (HSV infection, Kaposi's sarcoma (KS, and idiopathic ulceration. Gastric disease, though less common than esophageal disease, frequently involves CMV, Mycobacterium avium-intracellulare (MAI, and neoplasia (KS, lymphoma. Small bowel biopsies and intestinal aspirates from HIV-infected patients often show HIV enteropathy, MAI, protozoa (Giardia, Isospora, Cryptosporidia, amebae, Microsporidia, and helminths (Strongyloides stercoralis. Colorectal biopsies demonstrate viral (CMV, HSV, bacterial (Clostridia, Salmonella, Shigella, Campylobacter, fungal (cryptococcosis, histoplasmosis, and neoplastic (KS, lymphoma processes. Herein, we review HIV-associated GI pathology, with emphasis on common endoscopic biopsy diagnoses.

  19. Addiction and sexually transmitted disease (STD), human immunodeficiency virus, (HIV), and acquired immune deficiency syndrome (AIDS): their mutual interactions. (United States)

    Adrian, Manuella


    We explore the links between substance use, misuse, addiction, and dependency1 and sexuality, sexually transmitted diseases (STD), human immunodeficiency virus (HIV), and acquired immune deficiency syndrome (AIDS) to increase our awareness of their interdependence and to identify new ways to perceive, judge, and intervene (or not to) with associated problems. We consider the sociocultural and economic context in which these behaviors occur; the impact these behaviors have on one another; the personal opinions and attitudes; the religious, moral, or political beliefs and agendas; the physiological and fiscal constraints; and theories of rational decision-making and psychological motivation that act to increase or reduce the incidence of these behaviors and their sequellae, while hindering or facilitating prevention, harm reduction, and treatment interventions. Mechanisms of epidemic spread of STDS/HIV/AIDS are presented in the Appendix. Each of these terms are loaded "container concepts" that are culture-bound and stakeholder-driven and whose dimensions are less than consensus-based. They represent a range of meanings, uses, and misuses in an ongoing politicalized area of human and systemic functioning and adaptations.

  20. The relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease. (United States)

    Capitanio, J P; Mendoza, S P; Baroncelli, S


    Studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. The present study examined personality using techniques similar to those employed in human personality research. Adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. Approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (SIV) and exposed to socially stable or socially unstable conditions. Behavior, viral load (SIV RNA), plasma cortisol concentrations, and the IgG response to SIV and to rhesus cytomegalovirus were measured at regular intervals. Multiple regression analyses revealed that the four personality dimensions (Sociability, Confidence, Equability, Excitability) were correlated with various measures. Following inoculation with SIV, animals higher in Sociability showed a more rapid decline in plasma cortisol concentrations, elevations in the anti-RhCMV IgG response, and a decline in SIV RNA. The results indicate that personality factors in rhesus monkeys do have physiological correlates that have significance for disease processes and that in the context of a social manipulation, Sociability, reflecting the tendency to engage in affiliative interactions, is an important factor in explaining outcome measures at early time points. Copyright 1999 Academic Press.

  1. Prevalence and predictors of chronic kidney disease in newly diagnosed human immunodeficiency virus patients in Owerri, Nigeria

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    E N Anyabolu


    Full Text Available Human immunodeficiency virus (HIV infection is a common cause of chronic kidney disease (CKD in Sub-Saharan Africa. This study aims at identifying the prevalence and predictors of CKD in newly diagnosed HIV patients in Owerri, South East Nigeria. This was a cross-sectional study consisting of 393 newly diagnosed HIV-seropositive subjects and 136 age- and sex-matched seronegative subjects as controls. CKD was defined as 24-hour urine protein (24-HUP ≥0.3 g and/or glomerular filtration rate (GFR < 60 ml/min. Subjects were recruited from the HIV clinic and the Medical Outpatient Department of Federal Medical Centre, Owerri. Clinical and anthropometric data were collected. Relevant investigations were performed, including HIV screening and relevant urine and blood investigations. The mean age of the HIV subjects was 38.84 ± 10.65 years. CKD was present in 86 (22.9% HIV subjects and 11 (8.l % controls. Low waist circumference (WC, high serum creatinine, high spot urine protein/creatinine ratio (SUPCR, high 24-HUP/creatinine Ratio (24-HUPCR, high 24-HUP/osmolality Ratio (24-HUPOR predicted CKD in HIV subjects. CKD prevalence is high (22.9% among newly diagnosed HIV patients in South East Nigeria. The predictors of CKD included WC, serum creatinine, SUPCR, 24-HUPCR, and 24-HUPOR.

  2. Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease (United States)

    Kelsen, Judith R.; Dawany, Noor; Moran, Christopher J.; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S.; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F.; Daly, Mark; Sullivan, Kathleen E.; Baldassano, Robert N.; Devoto, Marcella


    Background & Aims Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed ≤5 y of age, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Methods Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (ages 3 weeks to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by post-processing and variant calling. Following functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency 1 Mbp of coding sequence, were selected from the whole exome data. Our analysis revealed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. Conclusions In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants. PMID:26193622

  3. Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Hirschhorn, R.; Nicknam, M.N.; Eng, F.; Yang, D.R.; Borkowsky, W. (New York Univ. Medical School of Medicine, NY (United States))


    Mutations at the adenosine deaminase (ADA) locus result in a spectrum of disorders, encompassing a fulminant neonatal onset severe combined immunodeficiency (SCID) and childhood onset immunodeficiency, as well as apparently normal immune function. The extent of accumulation of the toxic metabolite, deoxyATP, correlates directly with severity of disease. The authors have now determined the mutations on both alleles of a child with fulminant, neonatal onset ADA SCID and accumulation of extremely high concentrations of deoxyATP. The genotype was consistent with the severely affected phenotype. One allele carried a large deletion that arose by non-homologous recombination and included the first five exons and promoter region. The second allele carried a missense mutation (G[sup 649]A) resulting in replacement of Glu[sup 217], an amino acid involved in the catalytic site, by Lys and predicting a major alteration in charge. Expression of the mutant cDNA on Cos cells confirmed that the mutation abolished enzyme activity. The authors have previously reported that a missense mutation at the preceding codon is similarly associated with neonatal onset ADA SCID and accumulation of extremely high deoxyATP. These findings suggest that genotype-phenotype correlations may be apparent for ADA SCID, despite the role that random variation in exposure to environmental pathogens may play in the initial phenotype. Such genotype-phenotype correlations may be important to consider in evaluating results of ongoing trials of [open quotes]gene[close quotes] and enzyme replacement therapy. 50 refs., 5 figs., 2 tabs.

  4. Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: Analysis of cost-effectiveness based on French real field data. (United States)

    Clément, Marie Caroline; Mahlaoui, Nizar; Mignot, Cécile; Le Bihan, Christine; Rabetrano, Hasina; Hoang, Ly; Neven, Bénédicte; Moshous, Despina; Cavazzana, Marina; Blanche, Stéphane; Fischer, Alain; Audrain, Marie; Durand-Zaleski, Isabelle


    The inclusion of severe combined immunodeficiency (SCID) in a Europe-wide screening program is currently debated. In making a case for inclusion in the French newborn screening program, we explored the costs incurred and potentially saved by early management of SCID. For test costs, a microcosting study documented the resources used in a laboratory piloting a newborn screening test on Guthrie cards using the T-cell receptor excision circle quantification method. For treatment costs, patients with SCID admitted to the national reference center for primary immunodeficiency in France between 2006 and 2010 were included. Costs of admission were estimated from actual national production costs. We estimated the costs for patients who underwent early versus delayed hematopoietic stem cell transplantation (HSCT; age, ≤3 vs. >3 months, respectively). The unit cost of the test varied between €4.69 and €6.79 for 33,800 samples per year, depending on equipment use and saturation. Of the 30 patients included, 27 underwent HSCT after age 3 months. At 1 year after HSCT, 10 of these had died, and all 3 patients undergoing early transplantation survived. The medical costs for HSCT after 3 months were €195,776 (interquartile range, €165,884-€257,160) versus €86,179 (range, €59,014-€272,577) when performed before 3 months of age. In patients undergoing late transplantation, active infection contributed to high cost and poor outcome. Early detection of SCID could reduce the cost of treatment by €50,000-100,000 per case. Assuming a €5 unit cost per test, the incidence required to break even is 1:20,000; however, if the survival advantage of HSCT before 3 months is confirmed, universal screening is likely to be cost-effective. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus


    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation....

  6. Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease. (United States)

    Meltzer, M S; Gendelman, H E


    We have presented evidence in this review for the following: 1. Macrophages are likely the first cell infected by HIV. Studies document recovery of HIV into macrophages in the early stages of infection in which virus isolation in T cells is unsuccessful and detectable levels of antibodies against HIV are absent. 2. Macrophages are major tissue reservoirs for HIV during all stages of infection. Unlike the lytic infection of T cells, many HIV-infected macrophages show little or no virus-induced cytopathic effects. HIV-infected macrophages persist in tissue for extended periods of time (months) with large numbers of infectious particles contained within intracytoplasmic vacuoles. 3. Macrophages are a vector for the spread of infection to different tissues within the patient and between individuals. Several studies suggest a "Trojan horse" role for HIV-infected macrophages in dissemination of infectious particles. The predominant cell in most bodily fluids (alveolar fluid, colostrum, semen, vaginal secretions) is the macrophage. In semen, for example, the numbers of macrophages exceed those of lymphocytes by more than 20-fold (Wolf and Anderson 1988). 4. Macrophages are major regulatory cells that control the pace and intensity of disease progression in HIV infection. Macrophage secretory products are implicated in the pathogenesis of CNS disease and in control of viral latency in HIV-infected T cells. This litany of events in which macrophages participate in HIV infection in man parallels similar observations in such animal lentivirus infections as visna-maedi or caprine arthritis-encephalitis viruses. HIV interacts with monocytes differently than with T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention.

  7. Reduction of the diagnostic window with a new combined p24 antigen and human immunodeficiency virus antibody screening assay. (United States)

    Gürtler, L; Mühlbacher, A; Michl, U; Hofmann, H; Paggi, G G; Bossi, V; Thorstensson, R; G-Villaescusa, R; Eiras, A; Hernandez, J M; Melchior, W; Donie, F; Weber, B


    In order to reduce the window phase between time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new fourth generation screening assays which permit a simultaneous detection of HIV antigen and antibody have been developed. In a multicenter study, a new automated fourth generation assay, Enzymun-Test HIV Combi (Boehringer Mannheim GmbH) was compared to third generation assay, p24 antigen tests and Western blot. A total of 37 seroconversion panels, samples of the early infection (n = 42), HIV-1 antibody positive sera, including subtypes A E, and O (n = 1118), HIV-2 positive samples (n = 252) and cell culture supernatants infected with different HIV-1 subtypes and HIV-2 (n = 50), blood donors (n = 6649), hospitalized patients (n = 475), HIV neg. sera with indeterminate Western blot (n = 32), potentially cross reactive serum samples (n = 435) and HIV negative specimens from Cameroon (n = 68) were tested. A total of 16 of 29 seroconversions were detected on average 8.5 days earlier with Enzymun-Test HIV Combi than HIV-1/HIV-2 3rd generation EIA (Abbott Laboratories). Overall, in the 29 panels investigated comparatively with the two assays, the mean time delay between Enzymun-Test HIV Combi and HIV-1/HIV-2 3rd generation EIA was 4.7 days. HIV antigen was detected in three out of 35 seroconversions one bleed earlier with HIV-1 Ag Monoclonal than with Enzymun-Test HIV Combi. Enzymun-Test HIV Combi showed a sensitivity of 100% for HIV antibody detection for HIV-1 group M and O and HIV-2 positive specimens. While p24 antigen of different HIV-1 subtypes was detected with Enzymun-Test HIV Combi in all the 49 cell culture supernatants, HIV Ag was not detected in an HIV-2 virus lysate. A total of 66 false positive results out of 7659 HIV negative samples were obtained with the Enzymun-Test HIV Combi. The specificity for unselected blood donors was 99.6%. The Enzymun-Test HIV Combi permits an earlier diagnosis of HIV infection than third generation

  8. Homozygosity for a novel adenosine deaminase (ADA) nonsense mutation (Q3>X) in a child with severe combined immunodeficiency (SCID)

    Energy Technology Data Exchange (ETDEWEB)

    Santisteban, I.; Arrendondo-Vega, F.X.; Kelly, S. [Duke Univ. Medical Center, Durham, NC (United States)]|[Hospital for Sick Children, Ontario (Canada)] [and others


    A Somali girl was diagnosed with ADA-deficient SCID at 7 mo; she responded well to PEG-ADA replacement and is now 3.3 yr old. ADA mRNA was undetectable (Northern) in her cultured T cells, but was present in T cells of her parents and two sibs. All PCR-amplified exon 1 genomic clones from the patient had a C>T transition at bp 7 relative to the start of translation, replacing Gln at codon 3 (AGA) with a termination codon (TGA, Q3>X). Patient cDNA (prepared by RT-PCR with a 5{prime} primer that covered codons 1-7) had a previously described polymorphism, K80>R, but was otherwise normal, indicating that no other coding mutations were present. A predicted new genomic BfaI restriction site was used to establish her homozygosity for Q3>X and to analyze genotypes of family members. We also analyzed the segregation of a variable Alu polyA-associated TAAA repeat (AluVpA) situated 5{prime} of the ADA gene. Three different AluVpA alleles were found, one of which was only present in the father and was not associated with his Q3>X allele. Because the father`s RBCs had only {approximately}15% of normal ADA activity, we analyzed his ADA cDNA. We found a G>A transition at bp 425 that substitutes Gln for Arg142, a solvent-accessible residue, and eliminates a BsmAI site in exon 5. ADA activity of the R142>Q in vitro translation product was 20-25% of wild type ADA translation product, suggesting that R142>Q is a new {open_quote}partial{close_quote} ADA deficiency mutation. As expected, Q3>X mRNA did not yield a detectable in vitro translation product. We conclude that the patient`s father is a compound heterozygote carrying the ADA Q3>X/R142>Q genotype. {open_quote}Partial{close_quote} ADA deficiency unassociated with immunodeficiency is relatively common in individuals of African descent. The present findings and previous observations suggest that {open_quote}partial{close_quote} ADA deficiency may have had an evolutionary advantage.

  9. Diabetes Mellitus, Preexisting Coronary Heart Disease, and the Risk of Subsequent Coronary Heart Disease Events in Patients Infected With Human Immunodeficiency Virus The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

    NARCIS (Netherlands)

    Worm, Signe W.; de Wit, Stephane; Weber, Rainer; Sabin, Caroline A.; Reiss, Peter; El-Sadr, Wafaa; D'Arminio Monforte, Antonella; Kirk, Ole; Fontas, Eric; Dabis, Francois; Law, Matthew G.; Lundgren, Jens D.; Friis-Møller, Nina


    Background-Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact of DM

  10. Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady. (United States)

    Johnson, Raymond M; Bergmann, Kelly R; Manaloor, John J; Yu, Xiaoqing; Slaven, James E; Kharbanda, Anupam B


    Background.  Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV) + adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A + plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum. Methods.  A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV + subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data. Results.  Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis. Conclusions.  This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD.

  11. Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India

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    Parnita Harsh


    Full Text Available Background/Aims: Patients with inflammatory bowel disease (IBD often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV and hepatitis C (HCV and human immunodeficiency virus (HIV. In the present study, we assessed the prevalence of these infections in patients with IBD.Methods: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327 who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method. HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%.Results: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541 had HBV, 1.7% (9/517 had HCV, and 0.2% (1/499 had HIV. Among the 327 patients with CD, 2.8% (8/288 had HBV, 0.7% (2/273 had HCV, and 0% (0/277 had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67, 1.8% (1/57, and 1.2% (1/84, respectively.Conclusions: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.

  12. The clinical impact of immunodeficiency and viraemia in the era of combined antiretroviral therapy for HIV-1 infection

    NARCIS (Netherlands)

    Zhang, S.


    Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of

  13. Rapid disease progression in human immunodeficiency virus type 1-infected individuals with adverse reactions to trimethoprim-sulfamethoxazole prophylaxis

    NARCIS (Netherlands)

    Veenstra, J.; Veugelers, P. J.; Keet, I. P.; van der Ven, A. J. A. M.; Miedema, F.; Lange, J. M.; Coutinho, R. A.


    We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid

  14. Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

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    Anderson Dik Wai Luk


    Full Text Available BackgroundSevere combined immunodeficiency (SCID is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH has been associated with earlier diagnosis.ObjectiveThe aim of this study was to identify the clinical features that affect age at diagnosis (AD and time to the diagnosis of SCID.MethodsFrom 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP, and AD were selected for study.ResultsA total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57. A total of 29 patients had a positive FH. Candidiasis (n = 27 and bacillus Calmette–Guérin (BCG vaccine infection (n = 19 were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002 and diagnosis by 2 months (p = 0.008, but not shorter time to diagnosis (p = 0.494. Candidiasis was associated with later AD by 2 months (p = 0.008 and longer time to diagnosis by 0.55 months (p = 0.003. BCG infections were not associated with age or time to diagnosis.ConclusionFH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of

  15. Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection. (United States)

    Thobakgale, Christina F; Prendergast, Andrew; Crawford, Hayley; Mkhwanazi, Nompumelelo; Ramduth, Danni; Reddy, Sharon; Molina, Claudia; Mncube, Zenele; Leslie, Alasdair; Prado, Julia; Chonco, Fundi; Mphatshwe, Wendy; Tudor-Williams, Gareth; Jeena, Prakash; Blanckenberg, Natasha; Dong, Krista; Kiepiela, Photini; Coovadia, Hoosen; Ndung'u, Thumbi; Walker, Bruce D; Goulder, Philip J R


    A broad Gag-specific CD8(+) T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8(+) T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P = 0.007). Slow progressors tended to make CD8(+) T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8(+) T-cell responses generated in the child and through the transmission of low-fitness viruses by the

  16. Sexually transmitted diseases in homosexual and bisexual males from a cohort of human immunodeficiency virus negative volunteers (Project Horizonte, Belo Horizonte, Brazil

    Directory of Open Access Journals (Sweden)

    Lignani Jr L


    Full Text Available Sexually transmitted diseases (STD are very frequent in the whole world. Males who do not use a condom during their sexual relations are at great risk. We report cases of STD during six months of observation, among homosexual/bisexual males who participate in the Project Horizonte. There were 16 cases of genital warts, 6 cases of human immunodeficiency virus infection, 24 cases of unspecific urethritis, 28 cases of herpes simplex virus infection, 30 cases of syphilis, 58 cases of gonorrhea and 84 cases of pediculosis. We concluded that a condom must be used in all sexual relations and new counseling techniques are needed, to avoid this situation.

  17. Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency

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    Samantha L. Ginn


    Full Text Available In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.

  18. Advances of gene therapy for primary immunodeficiencies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Fabio Candotti


    Full Text Available In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases.

  19. Two unique mutations in the interleukin-2 receptor gamma chain gene (IL2RG) cause X-linked severe combined immunodeficiency arising in opposite parental germ lines

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M.; Pepper, A.E. [National Institutes of Health, Bethesda, MD (United States)


    The gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human X13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). 27 X-linked SCID mutations have been found in our laboratory. Single strand conformation polymorphism (SSCP) analysis of genomic DNA using primers flanking each of the 8 exons was followed by direct sequencing of abnormally migrating fragments from SCID patients and family members. A 9 bp in-frame duplication insertion was found in IL2RG exon 5 of a patient from a large X-linked SCID pedigree; the resulting duplication of 3 extracellular amino acids, including the first tryptophan of the {open_quotes}WSXWS{close_quotes} cytokine binding motif, is predicted to disrupt interaction of the cytokine receptor chain with its ligand. Genetic linkage studies demonstrated that the grandmaternal X chromosome associated with SCID was contributed to 3 daughters, 2 obligate carriers and 1 woman of unknown status. However, this grandmother`s genomic DNA did not contain the insertion mutation, nor did she have skewed X-chromosome inactivation in her lymphocytes. That both obligate carrier daughters, but not the third daughter, had the insertion proved the grandmother to be a germline mosaic. A second proband had X-linked SCID with a branch point mutation due to substitution of T for A 15 bp 5{prime} of the start of IL2RG exon 3. This mutation resulted in undetectable IL2RG mRNA by Northern blot. Linkage analysis and sequencing of IL2RG DNA in this family proved the mutation to have originated in the germline of the proband`s grandfather, an immunocompetent individual who contributed an X chromosome with normal IL2RG to one daughter and a mutated X to the another.

  20. Positron Emission Tomographic Imaging of Iodine 124 Anti–Prostate Stem Cell Antigen–Engineered Antibody Fragments in LAPC-9 Tumor–Bearing Severe Combined Immunodeficiency Mice

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton


    Full Text Available The humanized antibody (hu1G8 has been shown to localize to prostate stem cell antigen (PSCA and image PSCA-positive xenografts. We previously constructed hu1G8 anti-PSCA antibody fragments and tested them for tumor targeting and the ability to image prostate cancer at early and late time points postinjection by positron emission tomography (PET. We now then compare the PET imaging and the radioactivity accumulation properties in prostate cancer tumors and nontarget tissues to determine the superior 124I-labeled hu1G8 antibody format. 124I-labeled diabody, minibody, scFv-Fc, scFv-Fc double mutant (DM, and parental IgG were administered into severe combined immunodeficiency (SCID mice bearing LAPC-9 xenografts and followed by whole-body PET imaging of mice at preselected time points. Regions of interest were manually drawn around tumor and nontarget tissues and evaluated for radioactivity accumulation. The 124I-hu1G8 IgG has its best time point for tumor high-contrast imaging at 168 hours postinjection. The 124I-hu1G8 minibody at 44 hours postinjection results in superior tumor high-contrast imaging compared to the other antibody formats. The 124I-hu1G8 minibody at 44 hours postinjection also has comparable percent tumor radioactivity compared to 124I-hu1G8 IgG at 168 hours postinjection. The 124I-hu1G8 minibody is the best engineered hu1G8 antibody format for imaging prostate cancer.

  1. Cutaneous manifestations of primary immunodeficiency

    NARCIS (Netherlands)

    Sillevis Smitt, Johannes H.; Kuijpers, Taco W.


    To show that skin symptoms help in the recognition of primary immunodeficiencies (PIDs). To analyze whether recent molecular data help in understanding genotype/phenotype relations. Erythroderma in Omenn syndrome may be caused by either mutations in genes associated with severe combined

  2. Severe Combined Immunodeficiency (For Parents) (United States)

    ... system . These disorders lead to reduced or malfunctioning T- and B-lymphocytes, the specialized white blood cells made in the bone marrow and the thymus gland to fight infection. When the immune system doesn' ...

  3. Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult. (United States)

    Chigonda, T G; Chatora, G T; Ngwende, G W; Miller, R F; Ferrand, R A


    A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood.

  4. Disseminated Mycoplasma orale infection in a patient with common variable immunodeficiency syndrome. (United States)

    Paessler, Michelle; Levinson, Arnold; Patel, Jean Baldus; Schuster, Mindy; Minda, Melanie; Nachamkin, Irving


    Human infection with Mycoplasma species other than M. pneumoniae are infrequent, but may be encountered in patients with immunodeficiencies. We report a patient with combined variable immunodeficiency that developed multiple abscesses and destructive bone disease caused by M. orale, an organism generally considered to be non-pathogenic. Molecular laboratory methods, 16S rRNA sequence analysis, were used to detect the organism directly in the surgical specimen and confirmed following isolating of the organism. This case demonstrates the importance of molecular technology in the diagnosis of difficult infectious disease problems.

  5. Systematic review of vestibular disorders related to human immunodeficiency virus and acquired immunodeficiency syndrome. (United States)

    Heinze, B; Swanepoel, D W; Hofmeyr, L M


    Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear. To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome. Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched. We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study. We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life.

  6. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

    Energy Technology Data Exchange (ETDEWEB)

    Sutjipto, S.; Pedersen, N.C.; Miller, C.J.; Gardner, M.B.; Hanson, C.V.; Gettie, A.; Jennings, M.; Higgins, J.; Marx, P.A. (Univ. of California, Davis (USA))


    Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.


    African Journals Online (AJOL)

    Rash (including Stevens-Johnson syndrome), insomnia, somnolence, dizziness, trouble concentrating, nightmares. Nausea, diarrhoea, anorexia, abdominal pain, fatigue, headache, insomnia, hypersensitivity reactions. tAvailable as a combined formulation Combivir®, the recommended dose is one tablet twice daily.

  8. Oral Manifestations of Human Immunodeficiency Virus Infection


    Epstein, Joel B.; Mathias, Richard G.


    The AIDS epidemic continues. All health-care workers, including physicians and dental personnel, may be instrumental in recognizing risk factors associated with Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection. Oral signs and symptoms of HIV infection may be the first presentation of the disease or may develop during the course of the disease and require management. Knowledge of the signs, symptoms and associated infections and tumours is needed to as...

  9. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. (United States)

    Ellis, Ronald J; Rosario, Debralee; Clifford, David B; McArthur, Justin C; Simpson, David; Alexander, Terry; Gelman, Benjamin B; Vaida, Florin; Collier, Ann; Marra, Christina M; Ances, Beau; Atkinson, J Hampton; Dworkin, Robert H; Morgello, Susan; Grant, Igor


    To provide updated estimates of the prevalence and clinical impact of human immunodeficiency virus-associated sensory neuropathy (HIV-SN) and neuropathic pain due to HIV-SN in the combination antiretroviral therapy (CART) era. Prospective, cross-sectional analysis. Clinical correlates for HIV-SN and neuropathic pain, including age, exposure to CART, CD4 levels, plasma viral load, hepatitis C virus infection, and alcohol use disorders, were evaluated in univariate and multivariate models. Six US academic medical centers. One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study. The presence of HIV-SN, defined by 1 or more clinical signs (diminished vibration or sharp sensation in the legs and feet; reduced ankle reflexes) in a distal, symmetrical pattern. Neuropathic pain was defined as aching, stabbing, or burning in a similar distribution. The effect on quality of life was assessed with the Medical Outcomes Study HIV Health Survey. We found HIV-SN in 881 participants. Of these, 38.0% reported neuropathic pain. Neuropathic pain was significantly associated with disability in daily activities, unemployment, and reduced quality of life. Risk factors for HIV-SN after adjustment were advancing age (odds ratio, 2.1 [95% confidence interval, 1.8-2.5] per 10 years), lower CD4 nadir (1.2 [1.1-1.2] per 100-cell decrease), current CART use (1.6 [1.3-2.8]), and past "D-drug" use (specific dideoxynucleoside analogue antiretrovirals) (2.0 [1.3-2.6]). Risk factors for neuropathic pain were past D-drug use and higher CD4 nadir. Neuropathic pain and HIV-SN remain prevalent, causing substantial disability and reduced quality of life even with successful CART. The clinical correlates of HIV-SN have changed with the evolution of treatment. These findings argue for redoubled efforts to determine HIV-SN pathogenesis and the development of symptomatic and neuroregenerative therapies.

  10. Atrial fibrillation and vascular disease-a bad combination

    DEFF Research Database (Denmark)

    Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian


    This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii......) the cardiovascular risk associated with the coexisting of the two diseases. The literature on this topic is relatively sparse, and we discuss results from both clinical trials and observational studies. There is a clear indication of an increased stroke risk associated with vascular disease in patients with atrial...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...

  11. The circulating T helper subsets and regulatory T cells in patients with common variable immunodeficiency with no known monogenic disease. (United States)

    Azizi, G; Mirshafiey, A; Abolhassani, H; Yazdani, R; Ansariha, F J; Shaghaghi, M; Mortazavi-Jahromi, S S; Noorbakhsh, F; Rezaei, N; Aghamohammadi, A


    Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis. The study population comprised 13 CVID patients and 13 healthy controls (HC). Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (IFN-γ, IL-17, IL-22, and IL-10), and cell subset specific transcription factors were evaluated before and after stimulation. The main clinical presentations of these patients were infections only and lymphoproliferations phenotypes, but no autoimmune and allergy phenotype were recorded. The frequencies of CD4+ T cells, Th17, and Treg cells were significantly reduced in CVID patients, however the subsets of Th1, Th1-like Th17 and Th22 cells were normal. After stimulation, retinoic-acid-orphan-receptor-C (RORC), and runt-related transcription factor 1 (RUNX1), IL17, and IL10 genes' expression in CVID patients were significantly lower, in comparison to the HC. Moreover, there was a lower concentration of IL-17 and IL-10 in cell culture supernatants of stimulated CD4+ T cells of CVID patients than HC. Our findings demonstrate that the imbalance of Th17 and Tregs could be an associated with infections only and lymphoproliferations phenotype in CVID patients without monogenic disorders.

  12. Update on the treatment of primary immunodeficiencies. (United States)

    García, J M; Español, T; Gurbindo, M D; Casas C, C


    A general review of advances in the treatment of Primary Immunodeficiencies (PID) has been performed. Treatment with immunoglobulins is indicated in cases of humoral immunodeficiencies and in selected cases of combined immunodeficiencies. The use of intramuscular immunoglobulins in the treatment of PID was abandoned after obtaining the intravenous immunoglobulins, since these are much more effective and have fewer adverse effects. Now subcutaneous immunoglobulins are also available. Immunoglobulins help to keep the patients free of symptoms and infections as these substances are able to neutralise infectious agents, modulate and promote the immune response and favour phagocytosis. Adverse effects have been reported in 5-15 % of patients receiving IVIg, and patients with deficiencies of subclasses of IgG with IgA deficiency and/or anti-IgA antibodies are at risk of severe reactions. No severe adverse effects of subcutaneous immuneglobulins have been reported and the medication can be self-administered. The efficacy and safety of IVIg and SCIg are similar and SCIg administered at home is associated with better quality of life. Stem Cell Transplantation (SCT) in Primary Immunodeficiencies is aimed at restoring the number and/or function of lymphocytes or phagocytes. Matched, related or unrelated donors, or related haploidentical donors are selected. HLA class II mismatched unrelated donors are avoided owing to the risk of severe graft versus host disease (GVHD). Stem cells are obtained from bone marrow, cord blood or peripheral blood. Prophylactic immunossupression (as well as donor T lymphocyte depletion in haploidentical and unrelated donors) is performed to avoid or minimize GVHD. Less toxic "reduced intensity" protocols now exist for pre-transplantation conditioning, indicated to avoid graft rejection if there is residual T-lymphocyte immunity in the host. In the majority of Severe Combined Immunodeficiencies (SCID), SCT results in T lymphocytes graft and the

  13. Spectrum of Disease Caused by Rhodococcus equi in Human Immunodeficiency Virus Infection: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sandra K Willsie-Ediger


    Full Text Available Since the first report of Rhodococcus equi infection in an acquired immune deficiency syndrome patient in 1986, seven additional cases have been described. A patient is described in whom the diagnosis was delayed due to misidentification of the organism as an atypical mycobacterial species. The literature regarding R equi infection in persons infected with the human immunodeficiency virus is reviewed. The most common presentation is one of a chronic, indolent pulmonary infiltrative disease (78%. Fever (78%, cough (67%, and hemoptysis (44% are frequently present. Coexistent opportunistic illnesses are common (67%. In the laboratory identification of this organism, it is important to communicate the clinical setting to the microbiologist and to recognize the potential for the organism to be overlooked as normal flora or a contaminant, or misidentified as an organism with similar phenotypic characteristics (Nocardia species or a rapidly growing mycobacterium. Based on experience in foals, therapy with erythromycin and rifampin is suggested.

  14. Combination Emtricitabine and Tenofovir Disoproxil Fumarate Prevents Vaginal Simian/Human Immunodeficiency Virus Infection in Macaques Harboring Chlamydia trachomatis and Trichomonas vaginalis (United States)

    Radzio, Jessica; Henning, Tara; Jenkins, Leecresia; Ellis, Shanon; Farshy, Carol; Phillips, Christi; Holder, Angela; Kuklenyik, Susan; Dinh, Chuong; Hanson, Debra; McNicholl, Janet; Heneine, Walid; Papp, John; Kersh, Ellen N.; García-Lerma, J. Gerardo


    Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P = .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity. PMID:26743846

  15. Recurrent intussusception, coeliac disease and cholelithiasis: A unique combination

    Directory of Open Access Journals (Sweden)

    Sinha C


    Full Text Available Authors report an 11-month-old female child, who presented with recurrent episodes of colicky abdominal pain and diarrhea. An abdominal ultrasound revealed small bowel intussusception. She was also noted to have a thick walled gall bladder and a solitary gallstone. Further investigations confirmed the diagnosis of coeliac disease. The combination of small bowel intussusception, coeliac disease and cholelithiasis is unique and has not been reported in the literature.

  16. Combining Unsupervised and Supervised Learning for Discovering Disease Subclasses


    Tucker, A; Bosoni, P; Bellazzi, R; Nihtyanova, S; Denton, C


    Diseases are often umbrella terms for many subcategories of disease. The identification of these subcategories is vital if we are to develop personalised treatments that are better focussed on individual patients. In this short paper, we explore the use of a combination of unsupervised learning to identify potential subclasses, and supervised learning to build models for better predicting a number of different health outcomes for patients that suffer from systemic sclerosis, a rare chronic co...

  17. Long-term outcomes of liver transplant patients with human immunodeficiency virus infection and end-stage-liver-disease: single center experience

    Directory of Open Access Journals (Sweden)

    Vernadakis S


    Full Text Available Abstract Objective Orthotopic-liver-transplantation (OLT in patients with Human-Immunodeficiency-Virus infection (HIV and end-stage-liver-disease (ESDL is rarely reported. The purpose of this study is to describe our institutional experience on OLT for HIV positive patients. Material and methods This is a retrospective study of all HIV-infected patients who underwent OLT at the University Hospital of Essen, from January 1996 to December 2009. Age, sex, HIV transmission-way, CDC-stage, etiology of ESDL, concomitant liver disease, last CD4cell count and HIV-viral load prior to OLT were collected and analysed. Standard calcineurin-inhibitors-based immunosuppression was applied. All patients received anti-fungal and anti-pneumocystis carinii pneumonia prophylaxis post-OLT. Results Eight transplanted HIV-infected patients with a median age of 46 years (range 35-61 years were included. OLT indications were HCV (n = 5, HBV (n = 2, HCV/HBV/HDV-related cirrhosis (n = 1 and acute liver-failure (n = 1. At OLT, CD4 cell-counts ranged from 113-621 cells/μl, and HIV viral-loads from Conclusions OLT in HIV-infected patients and ESLD is an acceptable therapeutic option in selected patients. Long-term survival can be achieved without HIV disease-progression under antiretroviral therapy and management of the viral hepatitis co-infection.

  18. 2017 HIV Medicine Association of Infectious Diseases Society of America Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With Human Immunodeficiency Virus. (United States)

    Bruce, R Douglas; Merlin, Jessica; Lum, Paula J; Ahmed, Ebtesam; Alexander, Carla; Corbett, Amanda H; Foley, Kathleen; Leonard, Kate; Treisman, Glenn Jordan; Selwyn, Peter


    Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:

  19. Molecular and genetic basis of X-linked immunodeficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M. (National Center for Human Genome Research, Bethesda, MD (United States))


    Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B cell-specific intracellular tyrosine kinase; HIGM, by mutations in the TNF-related CD40 ligand, through which T cells deliver helper signals by direct contact with B cell CD40; and XSCID, by mutations in the [gamma] chain of the lymphocyte receptor for IL-2. Each patient mutation analyzed to date has been unique, representing both a challenge for genetic diagnosis and management and an important resource for dissecting molecular domains and understanding the physiologic function of the gene products.

  20. Knowledge, attitude, and perception of disease among persons living with human immunodeficiency virus/acquired immuno deficiency syndrome: A study from a tertiary care center in North India. (United States)

    Gupta, Mrinal; Mahajan, Vikram K; Chauahn, Pushpinder S; Mehta, Karainder S; Rawat, Ritu; Shiny, T N


    Although modification of behavioral practices among human immunodeficiency virus (HIV)-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS). To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13) years. The majority, 112 (74.67%) patients were between 20 and 50 years of age and 116 (77.3%) patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2%) patients among affected males. Only 129 (86%) respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3%) respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7%) respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90%) patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.

  1. Chronic disease risk management: Combining genetic testing with ...

    African Journals Online (AJOL)

    Overwhelming evidence indicates that diet is a key environmental factor affecting the incidence of many chronic diseases treated by medical practitioners on a daily basis. Information available in public gene databases, combined with advanced molecular technologies and nutrition research, provides the opportunity for the ...

  2. Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Mogtomo Martin


    Full Text Available Abstract Background Women infected with human immunodeficiency virus (HIV may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV, HIV infection and Highly Active Antiretroviral Therapy (HAART on the development of Squamous Intraepithelial lesions (SILs. Out of the 70 HIV infected women from Douala -Cameroon (Central Africa that we included in the study, half (35 were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL. Results Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70 and 31.4% (22/70 respectively. Among the 22 HSIL-positive women, 63.6% (14/22 were not on antiretroviral therapy, while 36.4% (8/22 were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1. The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high. Conclusion These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.

  3. Testing for Human Immunodeficiency Virus (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  4. Recurrent Infections May Signal Immunodeficiencies (United States)

    ... Recurrent Infections May Signal Immunodeficiencies Share | Recurrent Infections May Signal Immunodeficiencies This article has been reviewed by ... common bacterial infections? If so, these recurrent infections may be a sign of an immunodeficiency disorder. The ...

  5. Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa. (United States)

    Drain, Paul K; Losina, Elena; Coleman, Sharon M; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N; Freedberg, Kenneth A; Bassett, Ingrid V


    Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality. We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality. Among 726 HIV-infected adults with median CD4 of 205 cells/mm3 (interquartile range, 79-350 cells/mm3), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20-5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26-6.73) MHR for all participants and a 4.55 (95% CI, 1.71-12.1) MHR for participants with CD4 ≤100 cell/mm3. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease. Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.

  6. Clinical-Epidemiological Pattern of Primary Immunodeficiencies in Malaysia 1987-2006: A 20 year experience in Four Malaysian Hospitals. (United States)

    Noh, L M; Nasuruddin, B A; Abdul Latiff, A H; Noah, R M; Kamarul Azahar, M R; Norzila, M Z; Zulkifli, I; Gill, H K; Nik Zainal, N I; Suhaimi, A W M; Nik Khairulddin, N Y; Maraina, H; Intan, H I; Mat, I; Shahnaz, M; B H O, Azizi


    To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007. Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.

  7. Association between feline immunodeficiency virus (FIV) plasma viral RNA load, concentration of acute phase proteins and disease severity. (United States)

    Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne


    Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Consanguinity and primary immunodeficiencies. (United States)

    Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima


    Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.

  9. RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations. (United States)

    Wasserman, Richard L; Greener, Benjamin N; Mond, James


    Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects. Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients. Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD). This product offers potential advantages over other available IG's for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition. In addition to its enhanced neutralizing anti-RSV activity and its polyclonal IG composition, there is preclinical data to support the use of RI-002 for humoral protection against other respiratory pathogens.

  10. Breadth of neutralizing antibody response to human immunodeficiency virus type 1 is affected by factors early in infection but does not influence disease progression. (United States)

    Piantadosi, Anne; Panteleeff, Dana; Blish, Catherine A; Baeten, Jared M; Jaoko, Walter; McClelland, R Scott; Overbaugh, Julie


    The determinants of a broad neutralizing antibody (NAb) response and its effect on human immunodeficiency virus type 1 (HIV-1) disease progression are not well defined, partly because most prior studies of a broad NAb response were cross-sectional. We examined correlates of NAb response breadth among 70 HIV-infected, antiretroviral-naïve Kenyan women from a longitudinal seroincident cohort. NAb response breadth was measured 5 years after infection against five subtype A viruses and one subtype B virus. Greater NAb response breadth was associated with a higher viral load set point and greater HIV-1 env diversity early in infection. However, greater NAb response breadth was not associated with a delayed time to a CD4(+) T-cell count of <200, antiretroviral therapy, or death. Thus, a broad NAb response results from a high level of antigenic stimulation early in infection, which likely accounts for prior observations that greater NAb response breadth is associated with a higher viral load later in infection.

  11. Orofacial manifestation of hematological disorders: Hemato-oncologic and immuno-deficiency disorders

    Directory of Open Access Journals (Sweden)

    Titilope A Adeyemo


    Full Text Available The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases with special reference to hemato-oncologic, immuno-deficiency disorders, and human immunodeficiency virus infection. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases with emphasis on hemato-oncologic and human immunodeficiency virus (HIV infection. Mesh phrases used in the search were: Oral diseases AND hematological disorders; orofacial diseases AND leukemias; orofacial lesions AND lymphomas; orofacial diseases AND multiple myeloma, orofacial manifestations AND HIV. The Boolean operator "AND" was used to combine and narrow the searches. The full texts of these articles were thoroughly examined. References in these articles also were manually searched non-Medline articles. Only relevant articles were selected for the review. Orofacial manifestation of malignant hematological diseases may present as primary clinical features due to infiltration of orofacial tissues, or as secondary due to the subsequent infiltration of normal bone marrow elements, or tertiary due to the side effects of the treatment. HIV-associated orofacial lesion may be a clinical indicator of HIV infection in otherwise healthy, undiagnosed individuals; an early clinical feature of HIV infection; clinical markers for the classification and staging of HIV disease or may be a predictor of HIV disease progression. Orofacial manifestations of malignant hematological diseases and HIV infection are not uncommon findings in clinical practice. These manifestations may be clinical indicators of hematologic disorders in otherwise healthy, undiagnosed individuals.

  12. The management of combined coronary artery disease and peripheral vascular disease

    NARCIS (Netherlands)

    A. Cassar (Andrew); D. Poldermans (Don); C.S. Rihal (Charanjit); B.J. Gersh (Bernard)


    textabstractCoronary artery disease (CAD) and peripheral vascular disease (PVD) remain highly prevalent in the population due to population ageing, smoking, diabetes, unhealthy lifestyles, and the epidemic of obesity, and frequently coexist. The management of combined CAD and PVD is a common

  13. Cost Analysis and Performance Assessment of Partner Services for Human Immunodeficiency Virus and Sexually Transmitted Diseases, New York State, 2014. (United States)

    Johnson, Britney L; Tesoriero, James; Feng, Wenhui; Qian, Feng; Martin, Erika G


    To estimate the programmatic costs of partner services for HIV, syphilis, gonorrhea, and chlamydial infection. New York State and local health departments conducting partner services activities in 2014. A cost analysis estimated, from the state perspective, total program costs and cost per case assignment, patient interview, partner notification, and disease-specific key performance indicator. Data came from contracts, a time study of staff effort, and statewide surveillance systems. Disease-specific costs per case assignment (mean: $580; range: $502-$1,111), patient interview ($703; $608-$1,609), partner notification ($1,169; $950-$1,936), and key performance indicator ($2,697; $1,666-$20,255) varied across diseases. Most costs (79 percent) were devoted to gonorrhea and chlamydial infection investigations. Cost analysis complements cost-effectiveness analysis in evaluating program performance and guiding improvements. © Health Research and Educational Trust.

  14. Restoring the balance: immunotherapeutic combinations for autoimmune disease

    Directory of Open Access Journals (Sweden)

    Dawn E. Smilek


    Full Text Available Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.

  15. Allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies: Hospital Israelita Albert Einstein experience. (United States)

    Fernandes, Juliana Folloni; Kerbauy, Fabio Rodrigues; Ribeiro, Andreza Alice Feitosa; Kutner, Jose Mauro; Camargo, Luis Fernando Aranha; Stape, Adalberto; Troster, Eduardo Juan; Zamperlini-Netto, Gabriele; Azambuja, Alessandra Milani Prandini de; Carvalho, Bruna; Dorna, Mayra de Barros; Vilela, Marluce Dos Santos; Jacob, Cristina Miuki Abe; Costa-Carvalho, Beatriz Tavares; Cunha, Jose Marcos; Carneiro-Sampaio, Magda Maria; Hamerschlak, Nelson


    To report the experience of a tertiary care hospital with allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies. Seven pediatric patients with primary immunodeficiencies (severe combined immunodeficiency: n = 2; combined immunodeficiency: n = 1; chronic granulomatous disease: n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1) who underwent eight hematopoietic stem cell transplants in a single center, from 2007 to 2010, were studied. Two patients received transplants from HLA-identical siblings; the other six transplants were done with unrelated donors (bone marrow: n = 1; cord blood: n = 5). All patients had pre-existing infections before hematopoietic stem cell transplants. One patient received only anti-thymocyte globulin prior to transplant, three transplants were done with reduced intensity conditioning regimens and four transplants were done after myeloablative therapy. Two patients were not evaluated for engraftment due to early death. Three patients engrafted, two had primary graft failure and one received a second transplant with posterior engraftment. Two patients died of regimen related toxicity (hepatic sinusoidal obstruction syndrome); one patient died of progressive respiratory failure due to Parainfluenza infection present prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. Patients' status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.

  16. Human inmmunoglobulin in primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Sheffler Mendoza Selma


    Full Text Available Human immunoglobulin replacement therapy has become a corner- stone in the treatment of patients with primary immunodeficiencies (PID. Currently indicated as first-line therapy for predominantly antibody deficiencies, severe combined immunodeficiencies, and some well-defined syndromes with immunodeficiencies, it is also indicated as adjunct therapy in many other PID. Although considered a high-cost medication, elegant studies had showed that patients correctly treated with human immunoglobulin replacement therapy result in lower costs derived from their health- attention. Major benefits of immunoglobulin replacement therapy include but are not restricted to: protection against infectious processes, organ damage progression-arrest, immune modulation and quality-of-life improvement. Two modalities of treatment are currently used, intravenous and subcutaneous, each has clear advantages and disadvantages when compared to the other, which are presented in this article. The correct use of human immunoglobulin for the treatment of patients with PID translates in better medical-practices improving survival and quality of life of affected patients.

  17. [Peripheral arterial disease and cardiovascular risk factors among patients infected with human immunodeficiency virus: a comparison between hospital out-patients and patients in a prison]. (United States)

    Mauri Pont, Marta; Borrallo Almansa, Rosa Maria; Almada Rivas, Guido; Carbó Díez, Miriam; Solé Arnau, Rosa; García Restoy, Enric


    Cardiovascular disease among human immunodeficiency virus (HIV) infected patients is more frequent than in the general population. Peripheral arterial disease measured by ankle-brachial index (ABI) and cardiovascular risk factors (CVRF) is not well known in all groups of HIV-infected patients. Transversal study of HIV-infected patients >45 years, seen as outpatients in hospital (HO) in 2008 and patients institutionalized in a prison in 2009. Cardiovascular risk factors, information on the HIV infection and healthy lifestyles were evaluated. ABI was measured at rest and was considered pathological when a value ≤ 0.9 or ≥ 1.3 was obtained. We included 71 patients (mean age of 50.6 ± 6.9 years, 86% male), 32 HO and 39 in prison. The most prevalent CVRF was smoking (80.2%) followed by an altered lipid profile (63.3%). The evolution time of HIV infection was 13.1 ± 7.1 years. 74.6% of patients didn't follow a heart-healthy diet and 25% were sedentary. The ABI was low in 7 cases (9.8%) and ≥ 1.3 in one. Patients in prison were younger, the rate of smokers and of individuals with low HDL were higher, the time of evolution of the HIV infections was longer and they were less adherent to a heart-healthy diet than in HO, reaching in all cases statistical significance (P<.05). In our study there is a high prevalence of altered ABI. The most common CVRF is smoking, followed by the alteration of lipids. Patients in prison are more likely to be smokers, to have low HDL and they are less adherence to a heart-healthy diet. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  18. CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S


    . In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression...... of epithelial nuclear proliferation antigen, and elongation of the crypts. Later on, massive mononuclear cell infiltration, hypertrophy of all layers of the colon and occasional epithelial ulcerations were observed. At this stage, accumulations of IgA, IgM and small numbers of IgG1-, IgG2- and IgG3-secreting...

  19. Common Variable Immunodeficiency: Diagnosis, Management, and Treatment. (United States)

    Abbott, Jordan K; Gelfand, Erwin W


    Common variable immunodeficiency (CVID) refers to a grouping of antibody deficiencies that lack a more specific genetic or phenotypic classification. It is the immunodeficiency classification with the greatest number of constituents, likely because of the numerous ways in which antibody production can be impaired and the frequency in which antibody production becomes impaired in human beings. CVID comprises a heterogeneous group of rare diseases. Consequently, CVID presents a significant challenge for researchers and clinicians. Despite these difficulties, both our understanding of and ability to manage this grouping of complex immune diseases has advanced significantly over the past 60 years. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Combination of TMS and MRT to understand neurological diseases]. (United States)

    Hummel, F C


    Modern neuroimaging techniques, such as structural and functional magnetic resonance imaging (MRI) and non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) are increasingly used in the neuroscientific research of neurological disorders, such as stroke, tinnitus and movement disorders. These methods offer a non-invasive approach and especially in combination, not only the opportunity to add to the pathophysiological understanding of these disorders but also to provide information about the functional recovery and the natural course of the disease in a predictive way. Based on such knowledge therapeutic approaches can be adapted in a patient-tailored fashion to achieve the best therapeutic effects. Furthermore, these methods might provide additional non-invasive information for neurosurgical interventions reducing perioperative interventional risks.In the present article these aspects will be discussed with a focus on the combination of MRI and TMS especially addressed for the topic of recovery from stroke.

  1. Pancreatic cancer: systemic combination therapies for a heterogeneous disease. (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo


    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  2. A large left atrial lipoma combined with coronary artery disease. (United States)

    Liu, Yun; Zheng, Xiaomei; Du, Yu; Zhu, Zhicheng; Wang, Tiance; Xu, Rihao; Li, Dan; Liu, Kexiang


    Primary benign tumors of the heart are extremely rare and usually difficult to diagnose for their asymptomatic signs. A 66-year-old woman was admitted for shortness of breath caused by a large left atrial lipoma combined with coronary artery disease. Next, we successfully performed simultaneous curative surgery for the large cardiac lipoma and coronary artery bypass grafting with a "starfish" and no cardiopulmonary bypass was used.The patient was discharged on the eighth postoperative day in a good condition, and has remained asymptomatic at the 5-month follow-up. Lipomas are rare and difficult to diagnose, while computed tomography and computed tomography angiography can give us very important clues. Surgery is necessary. We can introduce a "starfish"to the operationand the cardiopulmonary bypass is unnecessary for the left lipoma with coronary artery disease.

  3. Appetite Suppressants, Cardiac Valve Disease and Combination Pharmacotherapy (United States)

    Rothman, Richard B.; Baumann, Michael H.


    The prevalence of obesity in the United States is a major health problem associated with significant morbidity, mortality and economic burden. Although obesity and drug addiction are typically considered distinct clinical entities, both diseases involve dysregulation of biogenic amine neuron systems in the brain. Thus, research efforts to develop medications for treating drug addiction can contribute insights into the pharmacotherapy for obesity. Here we review the neurochemical mechanisms of selected stimulant medications used in the treatment of obesity, as well as issues related to fenfluramine-associated cardiac valvulopathy. In particular, we discuss the evidence that cardiac valve disease involves activation of mitogenic 5-HT2B receptors by norfenfluramine, the major metabolite of fenfluramine. Advances in medication discovery suggest that novel molecular entities that target two different neurochemical mechanisms, i.e. “combination pharmacotherapy”, will yield efficacious anti-obesity medications with reduced adverse side-effects. PMID:19092640

  4. Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency? (United States)

    Kimura, Hiroshi


    Chronic active Epstein-Barr virus infection (CAEBV) is characterised by chronic or recurrent infectious mononucleosis-like symptoms, such as fever, hepatosplenomegaly, persistent hepatitis and extensive lymphadenopathy. Patients with CAEBV have high viral loads in their peripheral blood and/or an unusual pattern of EBV-related antibodies. This disease is rare but severe with high morbidity and mortality. Nearly three decades have passed since this disease was first identified, and recent advances in technology have increased our understanding of CAEBV pathophysiology. There is accumulating evidence that the clonal expansion of EBV-infected T or natural killer (NK) cells plays a central role in the pathogenesis of CAEBV. However, it remains unclear whether CAEBV is truly a monoclonal lymphoproliferative disorder. EBV-infected T or NK cells are able to evade the host cellular immune system due to the limited expression of viral proteins of reduced antigenicity. Recent studies suggest that infection of T or NK cells is a common event during primary EBV infection. A defect or single nucleotide polymorphism in host immune-modulating genes may allow for the expansion of virus infected cells giving rise to CAEBV. In this review, I summarise our current understanding of the pathogenesis of CAEBV and propose a model of CAEBV pathogenicity.

  5. Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus-Infected Patients With Nonalcoholic Fatty Liver Disease. (United States)

    Macías, Juan; Mancebo, María; Merino, Dolores; Téllez, Francisco; Montes-Ramírez, M Luisa; Pulido, Federico; Rivero-Juárez, Antonio; Raffo, Miguel; Pérez-Pérez, Montserrat; Merchante, Nicolás; Cotarelo, Manuel; Pineda, Juan A


    Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values EFV (P = .029). After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. NCT01900015.

  6. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood (United States)

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


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

  7. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements. (United States)


    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV) infection...

  8. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey. (United States)

    Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül


    Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

  9. Disease: H01181 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01181 T-cell immunodeficiency congenital alopecia and nail dystrophy (TIDAND) T-c...ell immunodeficiency congenital alopecia and nail dystrophy (TIDAND) is a severe combined immunodeficiency (

  10. [Current optimization of combined therapy for chronic obstructive pulmonary disease]. (United States)

    Popova, E N


    Testing the new combined bronchodilator Anoro Ellipta in different clinical trials gives to its high clinical efficacy and safety in chronic obstructive pulmonary disease. The drug contains the molecules of sustained-release selective β2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of umeclidinium bromide are in the competitive inhibition of the binding of acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles whereas in those of vilanterol are in that with the stimulation of intracellular adenylate cyclase. On days 1 and 24 after inhalation of the first dose of vilanterol and umeclidinium bromide, there was a significant increase in the forced expiratory volume in one second as compared to placebo. No clinical effects on QT interval on an electrocardiogram and cardiac rhythm were found. The benefits of an inhalation device (Ellipta) are its innovation design ensuring the effective delivery of an aerosol dose into the airway, convenience, and simplicity.

  11. Transurethral prostatectomy in human immunodeficiency virus ...

    African Journals Online (AJOL)

    Human immunodeficiency virus (HIV) infection is increasing world-wide and highly active antiretroviral treatment. (HAAT) is allowing afflicted individuals to live near normal life span and acquire surgical diseases of the aged as in the unaffected population. This pose occupational hazards to operating surgeons especially in ...

  12. Dental Practice, Human Immunodeficiency Virus Transmission and ...

    African Journals Online (AJOL)

    Background: More than 40 oral manifestations of human immunodeficiency virus (HIV) infection have been recorded and between 70% and 90% of persons with HIV infection will have at least one oral manifestation at some time during the course of their disease. Oral health-care workers (OHCWs) are therefore, key players ...

  13. Human Immunodeficiency Virus Seroconversion and Associated ...

    African Journals Online (AJOL)

    syphilis during ANC visit (P < 0.001) were found to be independent predictors of HIV seroconversion among pregnant women ... The syphilis screening among pregnant women in the ANC in Tanzania is based on the Venereal Disease ... booked at 4 months of gestation age [Table 1]. Human immunodeficiency virus ...

  14. Comparative periodontal status of human immunodeficiency virus ...

    African Journals Online (AJOL)

    P. M. B. 12003, Idi-Araba, Lagos, Nigeria. E-mail: Introduction. Exacerbated chronic periodontitis is part of the spectrum of periodontal diseases that has been described in association with the human immunodeficiency virus (HIV) infection. As far back as the early 1990s, studies exploring the possible.

  15. Pyoderma Vegetans: A Case Report in a Child Suspected to Primary Immunodeficiency and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Mahboubeh Mansouri


    Full Text Available Pyoderma vegetans (PV is a rare inflammatory disorder characterized by vegetating pustules and plaques affecting the skin and mucosal membranes. It is believed that this entity is mostly associated with inflammatory bowel disease (IBD, chronic malnutrition, human immunodeficiency virus (HIV, malignancies, and other immunocompromised states. Pyoderma vegetans occurs more commonly in young and middle-aged adults. There is no sex predilection for this entity. The lesions could heal spontaneously, but usually recur and become chronic. Our patient was an 11-year-old girl suspected to have primary combined immunodeficiency complicated by chronic recurrent vegetating pustular lesions on the face and postauricular area since one year of age. The histological features of the lesions were consistent with pyoderma vegetans. This is the first case of PV beginning from early infancy in the setting of primary immunodeficiency and in an unusual location.

  16. Sudden cardiac death in patients with human immunodeficiency virus infection

    National Research Council Canada - National Science Library

    Tseng, Zian H; Secemsky, Eric A; Dowdy, David; Vittinghoff, Eric; Moyers, Brian; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y


    ...) in patients with human immunodeficiency virus (HIV) infection. As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described...

  17. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D


    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  18. Associação de imunodeficiências primárias com doenças auto-imunes na infância Primary immunodeficiencies and autoimmune diseases association in childhood

    Directory of Open Access Journals (Sweden)

    Adriana Almeida de Jesus


    Pediatric Rheumatology Unit. A retrospective evaluation was performed in patients that presented arthritis as the first clinical manifestation of immunodeficiency. The humoral immunodeficiencies were classified into selective IgA deficiency, hypogammaglobulinemia and IgG subclass deficiency. RESULTS: Eleven patients (0.2% had primary immunodeficiency: selective IgA deficiency occurred in 8, common variable immunodeficiency in two, and IgG subclass deficiency in one. Five of the 11 patients had an acute arthritis and six patients a chronic nonerosive arthritis (JIA-like. From the 253 JIA patients evaluated, 70 had IgA level evaluation done and 6 (8.5% presented complete IgA deficiency (serum IgA < 7 mg/dl (JIA-like. From the 45 JSLE patients with IgA levels evaluated, 3 (6.6% had selective IgA deficiency diagnosis. CONCLUSION: The present study showed a low prevalence of humoral immunodeficiency in patients with rheumatic diseases. However, this association suggests that similar defects in immune response could be related to both diseases and that prospective studies are needed to elucidate this hypothesis.

  19. Adult hemorrhagic moyamoya disease: The paradoxical role of combined revascularization

    Directory of Open Access Journals (Sweden)

    Vikas C Jha


    Full Text Available Background: Moyamoya disease (MMD in adults often manifests with hemorrhage. Combined revascularization in hemorrhagic MMD is controversial as improvement in hemodynamics may be offset by hypervascularity-induced rebleeding. Aim: Long-term outcome assessment of adult patients from non-endemic region with hemorrhagic MMD undergoing combined revascularization. Setting: Tertiary care, academic setting. Materials and Methods: Both Suzuki′s internal carotid artery (ICA grade (1-6 and Mugikura′s posterior cerebral artery (PCA grade (1-4 were applied to 11 patients with hemorrhagic MMD (mean symptom duration 6.11±6.46 months undergoing direct [superficial temporal artery-middle cerebral artery (STA-MCA bypass] and indirect encephalomyosynangiosis (EMSA revascularization. They were clinically graded at follow-up (F/U as: excellent, preoperative symptoms resolved; good, preoperative symptoms resolved, neurological deficits remained; fair, symptom frequency decreased; and poor, symptoms unchanged/worsened. Digital subtraction angiogram/magnetic resonance angiography (DSA/MRA assessed the patency of anastomosis and cerebral hemodynamics as: 0 = non-patent; 1 = patent bypass, STA perfused recipient artery, moyamoya vessels unchanged; and, 2 = patent bypass, STA widely perfused MCA territory, moyamoya vessels diminished. An acetazolamide stimulated single photon emission computed tomography (SPECT study evaluated regional cerebral vascular reserve (RCVR. Results: Angiographic ICA grades were 5 (n=2, 4 (n=2, 3 (n=4, and 2 (n=3, and PCA grades were 1 (n=8 and 3 (n=3. At F/U (mean: 36.55±21.6 months, clinical recovery was excellent in eight and fair in one. Two patients developed delayed re-hemorrhage (in one at a site remote from previous bleed. F/U DSA/MRA (n=6 showed a good caliber, patent anastomosis with collaterals in five patients, and a narrow caliber anastomotic vessel in one patient. SPECT (n=6 revealed improved perfusion in two and normal

  20. Clinical and imaging considerations in primary immunodeficiency disorders: an update

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Eveline Y. [University of North Carolina at Chapel Hill, Department of Pediatrics, Chapel Hill, NC (United States); Ehrlich, Lauren [Yale School of Medicine, Department of Diagnostic Radiology, New Haven, CT (United States); Handly, Brian [University of North Carolina at Chapel Hill, Department of Radiology, Chapel Hill, NC (United States); Frush, Donald P. [Duke University Medical Center, Division of Pediatric Radiology, Durham, NC (United States); Buckley, Rebecca H. [Duke University Medical Center, Department of Pediatrics, Durham, NC (United States); Duke University School of Medicine, Department of Immunology, Durham, NC (United States)


    Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders. (orig.)

  1. Recent advances in primary immunodeficiencies: identification of novel genetic defects and unanticipated phenotypes. (United States)

    Pessach, Itai; Walter, Jolan; Notarangelo, Luigi D


    Primary immunodeficiencies (PIDs) have traditionally been defined according to their immunologic phenotype. Far from being concluded, the search for human genes that, when mutated, cause PID is actively being pursued. During the last year, four novel genetic defects that cause severe combined immunodeficiency and severe congenital neutropenia have been identified. At the same time, the immunologic definition of primary immunodeficiencies has been expanded by the recognition that genetic defects affecting innate immunity may result in selective predisposition to certain infections, such as mycobacterial disease, herpes simplex encephalitis, and invasive pneumococcal infections. Studies of genetically determined susceptibility to infections have recently shown that immunologic defects may also account for novel infectious phenotypes, such as malaria or leprosy. Finally, a growing body of evidence indicates that primary immunodeficiencies may present with a noninfectious clinical phenotype that may be restricted to single organs, as in the case of atypical hemolytic uremic syndrome or pulmonary alveolar proteinosis. Overall, these achievements highlight the importance of human models, which often differ from the corresponding animal models.

  2. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. (United States)

    Bode, Sebastian Fn; Ammann, Sandra; Al-Herz, Waleed; Bataneant, Mihaela; Dvorak, Christopher C; Gehring, Stephan; Gennery, Andrew; Gilmour, Kimberly C; Gonzalez-Granado, Luis I; Groß-Wieltsch, Ute; Ifversen, Marianne; Lingman-Framme, Jenny; Matthes-Martin, Susanne; Mesters, Rolf; Meyts, Isabelle; van Montfrans, Joris M; Pachlopnik Schmid, Jana; Pai, Sung-Yun; Soler-Palacin, Pere; Schuermann, Uta; Schuster, Volker; Seidel, Markus G; Speckmann, Carsten; Stepensky, Polina; Sykora, Karl-Walter; Tesi, Bianca; Vraetz, Thomas; Waruiru, Catherine; Bryceson, Yenan T; Moshous, Despina; Lehmberg, Kai; Jordan, Michael B; Ehl, Stephan


    Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome defined by clinical and laboratory criteria. Current criteria were created to identify patients with familial hemophagocytic lmyphohistiocytosis in immediate need of immunosuppressive therapy. However, these criteria also identify patients with infection-associated hemophagocytic inflammatory states lacking genetic defects typically predisposing to hemophagocytic lymphohistiocytosis. These patients include those with primary immunodeficiencies, in whom the pathogenesis of the inflammatory syndrome may be distinctive and aggressive immunosuppression is contraindicated. To better characterize hemophagocytic inflammation associated with immunodeficiencies, we combined an international survey with a literature search and identified 63 patients with primary immunodeficiencies other than cytotoxicity defects or X-linked lymphoproliferative disorders, presenting with conditions fulfilling current criteria for hemophagocytic lymphohistiocytosis. Twelve patients had severe combined immunodeficiency with <100/μL T cells, 18 had partial T-cell deficiencies; episodes of hemophagocytic lymphohistiocytosis were mostly associated with viral infections. Twenty-two patients had chronic granulomatous disease with hemophagocytic episodes mainly associated with bacterial infections. Compared to patients with cytotoxicity defects, patients with T-cell deficiencies had lower levels of soluble CD25 and higher ferritin concentrations. Other criteria for hemophagocytoc lymphohistiocytosis were not discriminative. Thus: (i) a hemophagocytic inflammatory syndrome fulfilling criteria for hemophagocytic lymphohistiocytosis can be the initial manifestation of primary immunodeficiencies; (ii) this syndrome can develop despite severe deficiency of T and NK cells, implying that the pathophysiology is distinct and not appropriately described as "lympho"-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc

  3. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S


    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...... in these tg scid mice. CD4+ T cells were found in the peritoneal cavity, in the mesenteric lymph nodes and in the intraepithelial layer and lamina propria of the gut. All CD4+ T cells were CD44+ (i.e. showed evidence of antigen-driven differentiation) and expressed the tg V beta 8.2 TcR beta-chain (TcR beta T......+). Only few CD4+ T cells expressed the tg V alpha 3+ TcR alpha-chain (TcR alpha T). cDNA was prepared from CD4+ T cells from spleen or mesenteric lymph nodes of individual male and female tg scid mice; sequence analyses of polymerase chain reaction-amplified, endogenous TcR alpha-chain (TcR alpha E...

  4. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

    DEFF Research Database (Denmark)

    Worm, Signe W; De Wit, Stephane; Weber, Rainer


    BACKGROUND: Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact...... of DM and preexisting CHD on the development of a new CHD episode among 33,347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). METHODS AND RESULTS: Over 159,971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV...... transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39, P=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05, P=0...

  5. Romidepsin alone or in combination with anti-CD20 chimeric antigen receptor expanded natural killer cells targeting Burkitt lymphoma in vitro and in immunodeficient mice. (United States)

    Chu, Yaya; Yahr, Ashlin; Huang, Brian; Ayello, Janet; Barth, Matthew; S Cairo, Mitchell


    Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL. This study examined the anti-tumor activity of romidepsin alone and in combination with anti-CD20 CAR exPBNKs against rituximab-sensitive and -resistant BL in vitro and in vivo. We found that romidepsin significantly inhibited both rituximab-sensitive and -resistant BL cell proliferation in vitro (P < 0.001) and induced cell death in rituximab-sensitive Raji (P < 0.001) and cell cycle arrest in rituximab-resistant Raji-2R and Raji-4RH (P < 0.001). Consistent with in vitro observations, we also found romidepsin significantly inhibited the growth of rituximab-sensitive and -resistant BL in BL xenografted NSG mice. We also demonstrated that romidpesin significantly induced the expression of Natural Killer Group 2, Member D (NKG2D) ligands MICA/B in both rituximab-sensitive and -resistant BL cells (P < 0.001) resulting in enhancement of exPBNK in vitro cytotoxicity through NKG2D. Finally, we observed the combination of romidepsin and anti-CD20 CAR exPBNK significantly induced cell death in BL cells in vitro, reduced tumor burden and enhanced survival in humanized BL xenografted NSG mice (p < 0.05). Our data suggests that romidepsin is an active HDAC inhibitor that also potentiates expanded NK and anti-CD20 CAR exPBNK activity against rituximab-sensitive and -resistant BL.

  6. Disease: H01181 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01181 T-cell immunodeficiency congenital alopecia and nail dystrophy (TIDAND) T-ce...ll immunodeficiency congenital alopecia and nail dystrophy (TIDAND) is a severe combined immunodeficiency (S...ata C Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia


    Directory of Open Access Journals (Sweden)

    E. G. Kuzmina


    Full Text Available Immune status of healthy people, patients with secondary immunodeficiency and allergic diseases is assessed. To reduce the number of characteristics of immunity (23 indicators to a number of the generalizing factors the multivariate analysis is used (principal component method. This method consistently reveals the principal components – independent functional complexes of interacting factors, with the characteristic of force of their interrelation. The principal components reflect communications between separate indicators and are located in size of their contribution to the total amount of information. The method is applied to structuring immunological indicators and a possibility of detection of features (distinctions of the immune status of patients with secondary immunodeficiency and allergic diseases. The method of principal components when it is applied to the assessment of immune status creates welldefined pattern of a functional condition of the immune system, accentuating main types of the reacting immunocompetent cells, their combinations and interaction. In the general immune status of healthy people (blood donors the T cell compartment (the first and second the principal components plays the major role. The second in importance components reflect the humoral immunity status. The indicators describing the response of the innate immunity (natural killer cells, the system phagocytic cells, follow them. Mathematical modeling reveals hierarchy of responses of innate and adaptive immunity, which is in agreement with established mechanisms of immune response. Differences of individual indicators of principal components of donors blood (norm, the patients with secondary immunodeficiency and allergic diseases built in the first, second and fourth to the principal components are detected. They group and display the status of 40% of the total amount (dispersion of immunological information taken in the analysis accentuating quantity and a

  8. Human Immunodeficiency Virus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Yasemin Arikan


    Full Text Available The incidence and prevalence of human immunodeficiency virus (HIV infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.

  9. Respiratory function in patients with coronary heart disease in combination with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    А. С. Клинкова


    Full Text Available The objective of the study was to assess the state of respiratory function (RF in patients with CHD and in patients with CHD combined with COPD. Also evaluated was the efficiency of pulmonary gas exchange, while taking into account the oxygen-utilization coefficient (OUC. RF was investigated in 73 patients with coronary heart disease (CHD and in 51 patients with CHD combined with COPD by means of a bodyplethysmography approach. In patients with CHD and COPD there was a significant reduction of the efficiency of pulmonary ventilation (OUC decreased by 24% as compared to the normal value against a background of bronchial conductivity. The patients with CHD without COPD showed a moderate decrease in RF reserves, with the effectiveness of pulmonary ventilation maintained at an optimal level.

  10. Combined prednisolone and pirfenidone in bleomycin-induced lung disease

    Directory of Open Access Journals (Sweden)

    Preyas J Vaidya


    Full Text Available Bleomycin is a cytostatic drug commonly employed in the treatment of Hodgkin's disease, seminomas, and choriocarcinoma. Bleomycin may induce a chronic pulmonary inflammation that may progress to fibrosis. So far, only corticosteroids have been used in the treatment of bleomycin-induced lung disease with variable results. Pirfenidone is an antifibrotic drug that has been approved for the treatment of idiopathic pulmonary fibrosis. We report two cases of bleomycin-induced lung disease treated successfully with pirfenidone and oral corticosteroids.

  11. Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. (United States)

    Heimall, Jennifer; Puck, Jennifer; Buckley, Rebecca; Fleisher, Thomas A; Gennery, Andrew R; Neven, Benedicte; Slatter, Mary; Haddad, Elie; Notarangelo, Luigi D; Baker, K Scott; Dietz, Andrew C; Duncan, Christine; Pulsipher, Michael A; Cowan, Mort J


    Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections. The average survival for SCID patients who have undergone transplantation currently is >70% at 3 years after transplantation, although this can vary significantly based on multiple factors, including age and infection status at the time of transplantation, type of donor source utilized, manipulation of graft before transplantation, graft-versus-host disease prophylaxis, type of conditioning (if any) utilized, and underlying genotype of SCID. In at least 1 study of SCID patients who received no conditioning, long-term survival was 77% at 8.7 years (range out to 26 years) after transplantation. Although a majority of patients with SCID will engraft T cells without any conditioning therapy, depending on genotype, donor source, HLA match, and presence of circulating maternal cells, a sizable percentage of these will fail to achieve full immune reconstitution. Without conditioning, T cell reconstitution typically occurs, although not always fully, whereas B cell engraftment does not, leaving some molecular types of SCID patients with intrinsically defective B cells, in most cases, dependent on regular infusions of immunoglobulin. Because of this, many centers have used conditioning with alkylating agents including busulfan or melphalan known to open marrow niches in attempts to achieve B cell reconstitution. Thus, it is imperative that we understand the potential late effects of these agents in this patient

  12. Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle. (United States)

    Praud, Christophe; Vauchez, Karine; Zongo, Pascal; Vilquin, Jean-Thomas


    Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C. The counts were integrated into a classical mathematical decline equation. After injection, human cells were essentially located in the endomysium, then they disappeared progressively from D0 to D28. The final number of integrated human nuclei was grossly determined at D2 after injection, suggesting that no more efficient fusion between donor myoblasts and host fibers occurs after the resolution of the local damages created by needle insertion. Almost 1% of implanted human cells occupied a satellite-like cell niche. Our mathematical model validated by histological counting provided a reliable quantitative estimate of human myoblast survival and/or incorporation into SCID muscle fibers. Informations brought by histological labelling and this mathematical model are complementary. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Primary immunodeficiencies in highly consanguineous North African populations. (United States)

    Barbouche, Mohamed-Ridha; Galal, Nermeen; Ben-Mustapha, Imen; Jeddane, Leïla; Mellouli, Fethi; Ailal, Fatima; Bejaoui, Mohamed; Boutros, Jeanette; Marsafy, Aisha; Bousfiha, Ahmed Aziz


    The study of inbred populations has contributed remarkably to the description of new autosomal recessive primary immunodeficiencies (PIDs). Here, we examine the pattern of PIDs in North African populations and assess the impact of highly prevalent consanguinity. This review reports on the current status of pediatricians' awareness of PIDs in Egypt, Morocco, and Tunisia, where awareness of PIDs is relatively recent. The phenotypic distribution of PIDs is reported and compared among the three countries and with other populations. Data analysis reveals a prevalence of autosomal recessive forms and a peculiar distribution of major PID categories, particularly more combined immunodeficiencies than antibody disorders. In these endogamous communities, molecular diagnosis is critical to developing a genetic-based preventive approach. The organization of diagnosis and care services in these resource-limited settings faces many obstacles. Autosomal recessive PIDs are overrepresented; thus, it is critical to continue investigation of these diseases in order to better understand the underlying mechanisms and to improve patient care. © 2011 New York Academy of Sciences.

  14. Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions. (United States)

    Kotler, Donald P


    Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

  15. Primary immunodeficiencies underlying fungal infections. (United States)

    Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne


    We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis. CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.

  16. Protein microarrays: a new tool for the study of autoantibodies in immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jacob Michael Rosenberg


    Full Text Available Autoimmunity is highly coincident with immunodeficiency. In a small but growing number of primary immunodeficiencies, autoantibodies are diagnostic of a given disease and implicated in disease pathogenesis. In order to best gain an understanding of the role of autoantibodies in immunodeficiencies and to discover novel autoantibodies, new proteomic tools are needed. Protein microarrays have the ability to screen for reactivity to hundreds to many thousands of unique autoantigens simultaneously on a single chip using minimal serum input. Here, we review the different types of protein microarrays and how they can be useful in framing the study of primary and secondary immunodeficiencies.

  17. Feline Immunodeficiency Virus in South America

    Directory of Open Access Journals (Sweden)

    Bruno M. Teixeira


    Full Text Available The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species. Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV causes an immune system disease in domestic cats (Felis catus involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs in South America.

  18. CC chemokine receptor 5 delta32 and CC chemokine receptor 2 64I polymorphisms do not influence the virologic and immunologic response to antiretroviral combination therapy in human immunodeficiency virus type 1-infected patients

    NARCIS (Netherlands)

    Wit, Ferdinand W. N. M.; van Rij, Ronald P.; Weverling, Gerrit Jan; Lange, Joep M. A.; Schuitemaker, Hanneke


    To investigate the influence of the CC chemokine receptor 2 64I and CC chemokine receptor 5 delta32 polymorphisms on the virologic and immunologic response of human immunodeficiency virus type 1 (HIV-1)-infected patients to highly active antiretroviral therapy, data from 4 clinical studies were

  19. Immunodeficiency in chronic sinusitis: recognition and treatment. (United States)

    Stevens, Whitney W; Peters, Anju T


    Chronic rhinosinusitis (CRS) is estimated to affect over 35 million people. However, not all patients with the diagnosis respond to standard medical and surgical treatments. Although there are a variety of reasons a patient may be refractory to therapy, one possible etiology is the presence of an underlying immunodeficiency. This review will focus on the description, recognition, and treatment of several antibody deficiencies associated with CRS, including common variable immunodeficiency (CVID), selective IgA deficiency, IgG subclass deficiency, and specific antibody deficiency (SAD). The diagnosis of antibody deficiency in patients with CRS is important because of the large clinical implications it can have on sinus disease management. CVID is treated with immunoglobulin replacement, whereas SAD may be managed symptomatically and sometimes with prophylactic antibiotics and/or immunoglobulin replacement.

  20. APOE2 and consanguinity: a risky combination for Alzheimer's disease. (United States)

    Kaur, M; Balgir, P P


    To investigate the association between APOE genotypes and Alzheimer's disease (AD) in elderly Indian subjects. The study also aims at the identification of consanguinity as disease risk factor for AD. A total of 100 Indian patients (26 consanguineous, 74 non-consanguineous), meeting criteria for probable or definite AD and 36 cognitively healthy, elderly unrelated control subjects (spouses), were included in the study. The APOE genotyping and statistical analyses (SPSS 7.5) was performed to determine the odds of AD according to APOE genotype. The analysis revealed increased prevalence of E4 allele in patients as compared with controls. The difference in prevalence of E3 and E4 alleles was found to be statistically significant between consanguineous patients and controls as well as non-consanguineous patients and controls. Compared to individuals with the APOE3/3, the odds of having AD were significantly increased among those with one or more copies of the E4 allele, even after adjusting with age and sex. An interesting outcome of the study is the higher prevalence of the E2 allele in consanguineous AD patients (in contrast to previously reported studies). The risk for AD was higher in consanguineous individuals with E2/4 genotype (1.62 fold), as compared to non-consanguineous individuals. The Results support that the APOE4 allele plays a role as a risk factor for AD and suggests that the APOE2 allele may not play a protective role in the development of AD in Indians, especially individuals with family history of consanguinity. The study hypothesises that the consanguinity modifies the disease risk associated with E2 allele, although this allele is considered protective. The less number of subjects from a broader population limits the study. The wide-ranging population and ethnicity-based studies in the most inbred groups of the world may provide comprehensive insight into this conclusion.

  1. Combined Alzheimer's disease and cerebrovascular staging explains advanced dementia cognition. (United States)

    Zea-Sevilla, María Ascensión; Fernández-Blázquez, Miguel Angel; Calero, Miguel; Bermejo-Velasco, Pedro; Rábano, Alberto


    The absence of a consensus system for full neuropathological evaluation limits clinicopathological studies and comparability between laboratories. Combined staging for Alzheimer's type and cerebral vascular pathology may allow a better classification of cases for clinical and cognitive correlation. Cognitive and postmortem neuropathological data were obtained from 70 brains donated to the Tissue Bank of the Centro de Investigación de Enfermedades Neurológicas (CIEN) Foundation according to recently developed staging schemes for Alzheimer's type and vascular pathology. Subjects belonged to a cohort of institutionalized patients with moderate or severe dementia and a mean follow-up period of 7 years. Cases were classified into three groups: Alzheimer's predominant (64.1%), vascular predominant (6.3%) and mixed pathology (29.6%). Significant differences were observed in Severe Mini-Mental State Examination and verbal fluency between the vascular predominant and the other groups of patients. The combination of scales measuring cerebral vascular and Alzheimer's type pathology allowed a classification of patients that reveals differences between groups in premortem cognitive features. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  2. Two CpG mutational hot spots in the X-linked interleukin-2 receptor gamma chain gene (IL2RG) may cause 15% of all human severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Center for Human Genome Research, Bethseda, MD (United States); Liu, X. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)


    Severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immune function, is caused by various autosomal gene defects, including adenosine deaminase (ADA) deficiency, as well as mutations in the X-linked IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2. Mutational analysis of IL2RG was performed using genomic DNA from males with SCID referred from genetics and immunology centers. Single strand conformation polymorphisms (SSCP) were sought by PCR amplification of each of the 8 IL2RG exons using labelled flanking primers. Sequence of exons with aberrant SSCP detected a majority of unique deleterious IL2RG mutations in 30 unrelated SCID patients. However, multiple mutations were seen at CpG dinucleotides, known to be C{yields}T transversion sites. cDNA 690-691 in exon 5 was mutated in 4 patients, 1 patient with each of the C{sub 690}{yields}T causing an Arg{yields}Cys substitution, and 1 with G{sub 691}{yields}A causing Arg{yields}His. Two other patients had SCID caused by a single mutation in IL2RG exon 7. This C{sub 879}{yields}T, also in a CpG, changed an Arg to STOP, resulting in loss of the SH2-related intracellular domain. In addition to our patients, 1 patient with each of the C{sub 690} and the C{sub 879} mutations have been reported by others, giving an overall incidence of 20% from our lab and 21% from all reported IL2RG SCID mutations. While ADA defects account for approximately 15% of SCID, a striking male SCID predominance suggest up to 70% of the cases are X-linked, due to IL2RG mutation. Thus, screening for mutations at the 2 CpG hot spots we have found in IL2RG can identify the genotype of as many SCID cases as are found by ADA testing.

  3. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples. (United States)

    Piloto, Obdulio; Nguyen, Bao; Huso, David; Kim, Kyu-Tae; Li, Yiwen; Witte, Larry; Hicklin, Daniel J; Brown, Patrick; Small, Donald


    The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is expressed at extremely high levels in ALL patients with mixed lineage leukemia rearrangements or hyperdiploidy and is sometimes mutated in these same patients. In this report, we investigate the effects of treating ALL cell lines and primary samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3 mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10 actually stimulated FLT3 activation, possibly as a result of antibody-mediated receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity, such an antibody could still prove efficacious against leukemia cells in vivo. In fact, IMC-EB10 treatment significantly prolonged survival and/or reduced engraftment of several ALL cell lines and primary ALL samples in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence-activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy reduced leukemic engraftment below the level of detection in these assays (IMC-EB10 treatment did not select for resistant cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10 cytotoxicity upon retransplantation. In vivo studies involving either partial depletion or activation of natural killer (NK) cells show that most of the cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an antibody, either naked or conjugated to radioactive

  4. Human immunodeficiency virus endocrinopathy

    Directory of Open Access Journals (Sweden)

    Uma Sinha


    Full Text Available Human immunodeficiency virus (HIV endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.

  5. Combined tamoxifen-lynestrenol treatment in benign breast disease. (United States)

    Cupceancu, B


    In order to avoid secondary induction of estrogens caused by tamoxifen treatment, tamoxifen was associated with the progestative lynestrenol in 48 menstrual women with benign breast disease (adenoma or fibroadenoma, cystic, simple or complex dysplasia). In one variant tamoxifen dosage was 20 mg (2 tablets) daily taken orally from day 5 to day 25 of the menstrual cycle, associated with 10 mg (2 tablets) of lynestrenol daily, only during the last 15 days. In another variant the above mentioned drugs were given concomitantly from day 10 to 15 of the cycle (according to cycle length) for 10 days. The average duration of the treatment was 4 cycles. The results are analysed according to surface percentage reduction of the main and associated lesions within the same case. In all cases of simple dysplasia, in 78% of the cases with complex dysplasia and in 54% of the adenomas, the lesions decreased to less than half their initial size, and in some instances the lesions disappeared altogether and the breasts became normally soft. Breast pain was improved or disappeared altogether in 96% of the cases. Despite its positive results the associated treatment used should be applied only in certain cases, especially those diagnozed as complex dysplasia and only in those medical units that have adequate diagnosis and treatment follow-up facilities.

  6. [Bechterew disease and top level sport: an attainable combination?]. (United States)

    Kleinjan, Marjolein; van Rijthoven, André W A M; Backx, Frank J G


    One 23-year-old and two 24- year-old athletes were diagnosed with ankylosing spondylitis. Because of their wish to compete in sport at the highest level, we considered the feasible extent and intensity of physical sports-load regarding the short-, middle- and long-term effects in this particular subgroup of ankylosing spondylitis patients. We could not find any published articles regarding the physical capacities of highly motivated athletes with ankylosing spondylitis. To give 'tailor made' advice to each athlete, we analysed these patients by using a standardized questionnaire, followed by analysis of the case history and a thorough physical examination. As a result we obtained an idea of the maximum individual feasible sports-load in relation to individual capacity for each athlete. Individual and disease characteristics, as well as the sport-specific physical load, can influence the physical capacity of the athlete. To register the effects of maximum sports-load in the middle and long term, and to work towards offering the best possible advice to athletes with ankylosing spondylitis, follow-up research in these 3 patients is advisable.

  7. Epidemiology of Primary Immunodeficiency in Iceland. (United States)

    Ludviksson, Bjorn R; Sigurdardottir, Sigurveig T; Johannsson, Johann Heidar; Haraldsson, Asgeir; Hardarson, Thorgeir O


    Primary immunodeficiencies (PID) are rare heterogeneous diseases. Little is known about the prevalence of PID in Iceland and no national registry exists. The aim of the study was to describe the epidemiology of PID in Iceland. Using The European Society's for Immunodeficiencies (ESID) criteria for PID, information about individuals with a known PID between 1990 and 2010 in Iceland were collected from inpatient registries of the National University Hospital of Iceland, the Department of Immunology and from clinical immunologists. Selective IgA deficiency, mannan binding lectin deficiency and secondary immunodeficiencies were excluded Sixty six individuals met the study criteria, 35 of them (53%) were females. Four patients died during the study period from PID- or treatment related complications and two moved abroad. In the beginning of 2011 there were 60 individuals living in Iceland with a known PID diagnosis meeting ESID's criteria. Estimated prevalence for PID in the Icelandic population of 318.452 habitants was 18.8 for 100.000 inhabitants. Predominantly antibody disorders comprised the largest category of PID in Iceland. The prevalence of PID is high in Iceland compared to reports from other nations. Our patient data are easily accessible and a central laboratory measures the immune parameters. This high prevalence may indicate that PID is more common than generally recognized.

  8. Autoimmune cytopenias related to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Vlasta Petric


    Full Text Available Background: Common variable immunodeficiency disorders are characterised by defective antibody production leading to recurrent infections. Noninfective complications are a consequence of autoimmunity, granuloma and polyclonal lymphoid infiltration. We often detect autoimmune cytopenias before primary immunodefciency is confirmed. Patients and methods: We report a case of 39-year old man with recurrent respiratory infections, autoimmune thrombocytopenia and haemolytic anemia who had common varible immunodeficiency confirmed. He had a lack of serum IgG, IgA and IgM, bronchiectasis, lymphadenopathy, splenomegaly, hepatic granuloma, autoimmune gastritis with B12 deficiency and Evans syndrome. We treated autoimmune cytopenias with methylprednisolon and cyclosporine. After substitution therapy with intravenous immunoglobulin the frequency of espiratory infections decreased. Occurrence of diarrhea is suspected for enteropathy, however, hystologic identification is required. Because of patologically changed gastric mucosa and signs of polyclonal lymphoid infiltration, the patient is at high risk for malignancy and the outcome of the disease remains unpredictable. Conclusions: Generally, we discover common variable immunodeficiency at management of noninfective complications, in wich intravenous immunoglobulin are not effective. Autoimmune cytopenias and some other complications are successfully treated with glucocorticoids. Careful monitorig of these patients is important because of a high risk for malignancy.

  9. [Primary immunodeficiencies in seriously ill children: Report of 3 clinical cases]. (United States)

    Yañez, Leticia; Lama, Pamela; Rivacoba, Carolina; Zamorano, Juanita; Marinovic, Maria Angélica


    Primary immunodeficiency diseases (PID) are congenital disorders secondary to an impaired immune response. Infections, autoimmune disorders, atopy, and lymphoproliferative syndromes are commonly associated with this disorder. To present and discuss 3 infants diagnosed with PID. The cases are presented of three patients with PID diagnosed during their first admission to a Paediatric Intensive Critical Care Unit. The first patient, a 4-month-old infant affected by a severe pneumonia, and was diagnosed as a Severe Combined Immunodeficiency Disease. The second patient was an 8-month-old infant with Candida lusitaniae mesenteric adenitis, and diagnosed with a Chronic Granulomatous Disease. The last patient, a 6-month-old infant presented with ecthyma gangrenosum and X-linked agammaglobulinaemia. PID should be suspected when an infectious disease does not responde to the appropriate therapy within the expected period. An update of each disease is presented. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Novel genome-editing tools to model and correct primary immunodeficiencies

    NARCIS (Netherlands)

    Ott De Bruin, Lisa M.; Volpi, Stefano; Musunuru, Kiran

    Severe combined immunodeficiency (SCID) and other severe non-SCID primary immunodeficiencies (non-SCID PID) can be treated by allogeneic hematopoietic stem cell (HSC) transplantation, but when histocompatibility leukocyte antigen-matched donors are lacking, this can be a high-risk procedure.

  11. Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk

    DEFF Research Database (Denmark)

    Franklin, J.G.; Paus, M.D.; Pluetschow, A.


    BACKGROUND: Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking. OBJECTIVES: Radiotherapy (RT), chemotherapy (CT) and combined chemo-radiotherapy (CRT) for newly...

  12. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. (United States)

    Bruyand, Mathias; Thiébaut, Rodolphe; Lawson-Ayayi, Sylvie; Joly, Pierre; Sasco, Annie Jeanne; Mercié, Patrick; Pellegrin, Jean Luc; Neau, Didier; Dabis, François; Morlat, Philippe; Chêne, Geneviève; Bonnet, Fabrice


    Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.

  13. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)


    Apr 6, 1974 ... Immunodeficiency diseases in infancy may be genetic or may result from an infection acquired during intra- uterine life. A precise aetiological diagnosis is important for genetic counselling purposes, prognosis and treatment. The case of a young female child with a combined immuno- deficiency disease ...

  14. Combination Comprising Parthenolide For Use In The Treatment Of Alzheimer's Disease And Other Neurodegenerative Disorders

    KAUST Repository

    Bajic, Vladimir B.


    The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer\\'s Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent, including an inhibitor of TLR4/MD-2/CD14, nAChR agonist, Resatorvid, Curcumin, Tilorone or a Tilorone analog, or a combination thereof.

  15. The combined effect of cancer and chronic diseases on general practitioner consultation rates.

    NARCIS (Netherlands)

    Heins, M.J.; Korevaar, J.C.; Donker, G.A.; Rijken, P.M.; Schellevis, F.G.


    Aim: More than two-thirds of cancer patients have one or more chronic diseases besides cancer. The purpose of this study was to get detailed insight into the combined effect of cancer and chronic diseases on general practitioner (GP) consultation rates. Methods: From the NIVEL Primary Care Database

  16. The combined effect of cancer and chronic diseases on general practitioner consultation rates

    NARCIS (Netherlands)

    Heins, M.J.; Korevaar, J.C.; Donker, G.A.; Rijken, P.M.; Schellevis, F.G.


    Aim: More than two-thirds of cancer patients have one or more chronic diseases besides cancer. The purpose of this study was to get detailed insight into the combined effect of cancer and chronic diseases on general practitioner (GP) consultation rates. Methods: From the NIVEL Primary Care Database

  17. [Innate immunity primary immunodeficiencies and infections]. (United States)

    Duchamp, M; Miot, C; Bustamante, J C; Picard, C


    The diagnosis of primary immunodeficiency diseases (PIDs) is important for the early and adaptive care of patients and their families. Among the various known PIDs, a number of them concern the innate immune system, which involve a set of cells and mechanisms involved in the host defense by a nonspecific and fast response. The majority of patients with innate immunity defects have a predisposition to one isolated type of infection (bacterial, viral, or fungal), dependent on the genetic defect involved. This article describes the different PIDs involving innate immunity and the immunological investigations allowing for their diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. [Acquired immunodeficiency syndrome in pediatric patients]. (United States)

    Molina Moguel, J L; Ruiz Illezcas, R; Forsbach Sánchez, S; Carreño Alvarez, S; Picco Díaz, I


    The object of this study was to determine how many of the patients treated at the Pediatric Odontology Clinic, a branch of the Maxillo-Facial Surgery Service at the Veinte de Noviembre Regional Hospital, ISSSTE, are VIH-positive of show serious manifestations of Acquired Immuno-Deficiency Syndrome (AIDS). For such purpose, 100 pediatric patients suffering from different systemic or local diseases were evaluated, the most common being hematological alterations. Results evidenced the presence of VIH in the blood of five of the pediatric subjects, all suffering from Hemophilia.

  19. Antigen Loading (e.g., Glutamic Acid Decarboxylase 65 of Tolerogenic DCs (tolDCs Reduces Their Capacity to Prevent Diabetes in the Non-Obese Diabetes (NOD-Severe Combined Immunodeficiency Model of Adoptive Cotransfer of Diabetes As Well As in NOD Mice

    Directory of Open Access Journals (Sweden)

    David P. Funda


    Full Text Available Tolerogenic DCs (tolDCs are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D. T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65, that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD-severe combined immunodeficiency (NOD-SCID recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein—ovalbumin (OVA. The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. application. These data document that mechanisms by which tol

  20. Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Lindsay Crickard

    Full Text Available Smallpox (variola virus is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs against vaccinia H3 (H3L and B5 (B5R, targeting both the mature virion (MV and extracellular enveloped virion (EV forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP studies examining severe combined immunodeficiency mice (SCID given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG. Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV. In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.

  1. Expansion of the biocontrol spectrum of foliar diseases in rice with combinations of rhizobacteria

    Directory of Open Access Journals (Sweden)

    Ismail Teodoro de Souza Júnior

    Full Text Available ABSTRACT The cultivation of irrigated rice is subject to the occurrence of various diseases, where damage causes losses in productivity. Alternatives are currently being sought to control these diseases, with biocontrol a viable possibility. With the aim of broadening the spectrum of action of biocontrol, this study evaluated the effect of combinations of biocontrol bacteria on rice blast (Pyricularia grisea, brown spot (Bipolaris oryzae and leaf scald (Gerlachia oryzae in rice plants. The effect of isolate combinations was assessed by microbiolization of seeds from the rice cultivar El Paso L144 with suspensions of the bacteria DFs185 (Pseudomonas synxantha, DFs223 (P. fluorescens, DFs306 (unidentified, DFs416 and DFs418 (Bacillus sp., used individually or in a combination of two, three or four compatible isolates. Seeds treated with Carboxin Thiram fungicide (T+F at a final dosage corresponding to 3 ml kg-1 were used as control. Considering the leaf diseases together, eight treatments significantly controlled all three diseases, and were superior to the treatment with fungicide. Among these treatments, seven were combinations. Only the DFs306 bacteria were able to control the three diseases when used individually. It can therefore be presumed that combinations of bacteria, when microbiolized in rice seeds, can broaden the spectrum of action for the control of rice blast, brown spot and leaf scald.

  2. [Parkinson's disease combined with overactive bladder syndrome treated with acupuncture and medication]. (United States)

    Chen, Yi-Liang'; Feng, Wei-Ju; Zhang, Xiao-Li


    To evaluate the therapeutic effect of Parkinson's disease combined with overactive bladder syndrome (GAB) treated with combined therapy of oral administration of Tolterodine with low dose and electroacuponcture. Sixty cases of Parkinson's disease combined with GAB were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each group. In both groups, Madopar basic doses were same, and anticholinergic agents such as Artane were stopped. In group A, Tolterodine was orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B, Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of urination and UPDRS III scores were observed, and the adverse reactions were recorded in both groups. After treatment, the frequency of average urination of 24 hours, frequency of incontinence of 24 hours and average urine volume at a time were obviously improved (all P Parkinson' s disease combined with GAB treated with combined therapy of Tolterodine with low dose and electroacupuncture is superior to that of complete dose of Tolterodine with oral administration, with less adverse reactions. And it also can improve the motor symptom of Parkinson's disease patients.

  3. Hepatitis C Virus and Human Immunodeficiency Virus Co-Infection ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are major health problems worldwide. HCV/HIV co-infection has been shown to increase the frequency of liver disease and also maternal-fetal transmission of HCV. Little data exist on the prevalence of co-infection of these viruses in ...

  4. Mathematical Analysis of a Model for Human Immunodeficiency ...

    African Journals Online (AJOL)


    ABSTRACT: The objective of this paper is to present a mathematical model formulated to investigate the dynamics of human immunodeficiency virus (HIV). The disease free equilibrium of the model was found to be locally and globally asymptotically stable. The endemic equilibrium point exists and it was discovered that the ...

  5. Awareness and practice of Human Immunodeficiency Virus And ...

    African Journals Online (AJOL)

    Background: Human Immunodeficiency Virus(HIV) and Hepatitis B Virus(HBV) infections are global viral diseases with various seroprevalence rates in different parts of the world. They share similar modes of transmission and are very important in Transfusion Medicine. Aim/Objective: To determine the level of awareness ...

  6. Sexual orientation and risk factors for Human Immunodeficiency ...

    African Journals Online (AJOL)

    The issue of homosexuality attracts global debate, given that this constitutes risk factor for sexually transmitted diseases. An exploration of socio-cultural, religious and sexual activities of lesbian, gay, bisexual, transgender and intersex sector would inform future Human Immunodeficiency Virus programming.

  7. Health care seeking among men with genital ulcer disease in South Africa: correlates and relationship to human immunodeficiency virus-1 and herpes simplex virus type 2 detection and shedding. (United States)

    Leichliter, Jami S; Lewis, David A; Sternberg, Maya; Habel, Melissa A; Paz-Bailey, Gabriela


    Episodic acyclovir therapy has been added to genital ulcer disease (GUD) syndromic management guidelines in several sub-Saharan African countries with human immunodeficiency virus (HIV) epidemics. We examined the correlates of health care seeking in men with GUD and its relationship to HIV-1 and herpes simplex virus type 2 outcomes. Men with GUD (n = 615) were recruited from primary health care clinics in Gauteng province, South Africa for a randomized controlled trial of episodic acyclovir therapy. We used baseline survey and sexually transmitted infection/HIV-testing data to examine delay in health care seeking (defined as time from ulcer recognition to baseline study visit). Median delay in health care seeking for GUD was 5 days, and one-quarter of men had previously sought care for the current ulcer. Previous care seekers were older, had more episodes of ulceration in the past year, and were more likely to test seropositive for HIV-1 and HSV-2. Delay in health care seeking was significantly associated with age, education level, and sex during the ulceration episode. Delays in care seeking were related to poorer HIV-1 outcomes; these findings were valid after controlling for advanced HIV. Interventions to help shorten the duration between ulcer recognition and health care seeking for men with GUD are needed.

  8. Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment

    Directory of Open Access Journals (Sweden)

    Elena Aguilera

    Full Text Available BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease.

  9. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease.

    Directory of Open Access Journals (Sweden)

    Tassiane Assíria Fontes Martins

    Full Text Available The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

  10. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease. (United States)

    Assíria Fontes Martins, Tassiane; de Figueiredo Diniz, Lívia; Mazzeti, Ana Lia; da Silva do Nascimento, Álvaro Fernando; Caldas, Sérgio; Caldas, Ivo Santana; de Andrade, Isabel Mayer; Ribeiro, Isabela; Bahia, Maria Terezinha


    The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

  11. Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group

    NARCIS (Netherlands)

    Dubé, M. P.; Sprecher, D.; Henry, W. K.; Aberg, J. A.; Torriani, F. J.; Hodis, H. N.; Schouten, J. [=Judith; Levin, J.; Myers, G.; Zackin, R.; Nevin, T.; Currier, J. S.


    Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy, These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the

  12. Screening for Human Immunodeficiency Virus (HIV) (United States)

    Understanding Task Force Recommendations Screening for Human Immunodeficiency Virus (HIV) The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Human Immunodeficiency Virus (HIV) . This ...



    Aketaeva Asem Sagimbekovna; Smailova Lazat Kenzhebekovna; Kabikenova Dinara Kenzhetaevna


    Determination of level of fallopian tube affect and assessment of fallopian tube state in women with natural sterility combined with reproductive diseases. The analysis of endoscopic surgery results was presented by sampling in 200 patients, of which 98 patients with natural sterility, 102 with secondary sterility. The patients with natural sterility were distributed by three groups: 1 group was made up with patients with natural sterility combined with endometriosis (n=33), ...

  14. Functional magnetic resonance imaging exploration of combined hand and speech movements in Parkinson's disease. (United States)

    Pinto, Serge; Mancini, Laura; Jahanshahi, Marjan; Thornton, John S; Tripoliti, Elina; Yousry, Tarek A; Limousin, Patricia


    Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task. Copyright © 2011 Movement Disorder Society.

  15. Collaborating to improve quality of life in patients with primary immunodeficiencies: World Prrimary Immunodeficiency Week (WPIW 2013

    Directory of Open Access Journals (Sweden)

    Sorensen Ricardo


    Full Text Available World Primary Immunodeficiency Week (WPIW 2013, is celebrated annually on 22-29 April. This year WPIW focuses on the need to test, diagnose and treat this primary immunodeficiency to promote its early detection and appropriate care. This year’s reflexions focuses on various regions of the world. The authors have taken stock of the situation in their respective areas of the world: Europe, Latin America, North Africa and Middle East, as well as Australia. Through a cross country analysis, it reflects on progress made to date to improve the life of patients with primary immunodeficiency diseases (PIDs and the challenges that remain to address. In addition the authors address the need for continued international collaboration amongst all relevant actors to drive better access to early diagnosis and appropriate treatment and ultimately improve the life of patients with PIDs.

  16. A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and Atherosclerosis. (United States)

    Bornfeldt, Karin E; Kramer, Farah; Batorsky, Anna; Choi, Jinkuk; Hudkins, Kelly L; Tontonoz, Peter; Alpers, Charles E; Kanter, Jenny E


    Diabetic kidney disease and atherosclerotic disease are major causes of morbidity and mortality associated with type 2 diabetes (T2D), and diabetic kidney disease is a major cardiovascular risk factor. The BTBR mouse strain with leptin-deficiency (Lepob) has emerged as one of the best models of human diabetic kidney disease. However, no T2D mouse model of combined diabetic kidney disease and atherosclerosis exists. Our goal was to generate such a model. To this end, the LDL receptor was targeted for degradation via IDOL (inducible degrader of the LDL receptor) overexpression, using a liver-targeted adeno-associated virus (AAV-DJ/8) in BTBR wild-type (WT) and BTBR Lepob (OB) mice. Liver-targeted IDOL-AAV-DJ/8 increased plasma LDL cholesterol, as compared with the control eGFP-AAV-DJ/8. IDOL-induced dyslipidemia caused formation of atherosclerotic lesions of an intermediate stage, which contained both macrophages and smooth muscle cells. BTBR OB mice exhibited diabetic kidney disease. IDOL-induced dyslipidemia worsened albuminuria and glomerular macrophage accumulation, but had no effect on mesangial expansion or podocyte numbers. Thus, by inducing hepatic degradation of the LDL receptor, we generated a T2D model of combined kidney disease and atherosclerosis. This model provides a new tool to study mechanisms, interactions, and treatment strategies of kidney disease and atherosclerosis in T2D. Copyright © 2017. Published by Elsevier Inc.

  17. Natural simian immunodeficiency virus transmission in mandrills: a family affair? (United States)

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique


    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

  18. The oral microbiome in human immunodeficiency virus (HIV)-positive individuals

    National Research Council Canada - National Science Library

    Kistler, James O; Arirachakaran, Pratanporn; Poovorawan, Yong; Dahlén, Gunnar; Wade, William G


    Human immunodeficiency virus (HIV) infection is associated with a range of oral conditions, and increased numbers of disease-associated microbial species have previously been found in HIV-positive subjects...

  19. Serofrequency of feline immunodeficiency virus and feline leukemia virus in cats of Araçatuba, São Paulo


    Sobrinho, Ludmila Silva Vicente [UNESP; Vides, Juliana Peloi [UNESP; Braga, Eveline Tozzi [UNESP; Gomes, Amélia Ana Domingues; Rossi,Claudio Nazaretian; Marcondes, Mary


    Feline immunodeficiency virus and feline leukemia represent important infectious diseases caused by retroviruses. This study aimed to investigate the prevalence of infection by feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in cats from the municipality of Araçatuba, São Paulo. Blood samples from 302 cats were collected and tested for the presence of antibodies against feline immunodeficiency virus and antigen of feline leukemia virus by ELISA ® Snap- Combo FIV-FeLV (IDE...

  20. Newcastle disease virus, rituximab, and doxorubicin combination as anti-hematological malignancy therapy

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    Al-Shammari AM


    Full Text Available Ahmed Majeed Al-Shammari,1 Huda Rameez,2 Maha F Al-Taee2 1Department of Experimental Therapy, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, 2Department of Biotechnology, College of Science, Baghdad University, Baghdad, IraqAbstract: Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou–Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies.Keywords: oncolytic viruses, virotherapy, combination therapy

  1. High specificity of V3 serotyping among human immunodeficiency virus type-1 subtype C infected patients with varying disease status and viral phenotype. (United States)

    Walker, Polly R; Cilliers, Tonie; Choge, Isaac A; Taylor, Natasha; Cohen, Sarah S; Morris, Lynn


    V3 serotyping is a technique for determining HIV-1 genetic subtype based on the binding of antibodies from patient sera or plasma to synthetic V3 peptides derived from subtype consensus sequences. Variation in the performance of this assay has been attributed to V3 sequence heterogeneity, the degree of which varies with patient disease progression, virus co-receptor usage, and genetic subtype. This study assessed the performance of a competitive peptide enzyme immunoassay (cPEIA) in samples from HIV-1 subtype C infected patients with varying disease profiles, including those with syncytium (SI) and non-syncytium-inducing (NSI) viruses. Out of 90 sera tested, 94.4% reacted strongly against the subtype C peptide. There was no significant difference in assay sensitivity among samples from advanced AIDS patients in which humoral immune response may be lower, nor among SI viruses which carry changes in the V3 sequence. Four samples were found to be cross-reactive with other subtypes and one acutely infected patient sample was non-reactive due to low anti-gp120 antibody titers. A significantly higher number of samples showed secondary reactivity to subtype A, compared to other subtypes (P < 0.005). In conclusion, the assay was able to identify HIV-1 subtype C infection with a high level of sensitivity (94%) irrespective of the stage of disease and therefore provides a valuable resource for the large-scale epidemiological monitoring of the spread of HIV-1 subtypes in South Africa.

  2. Mathematical models of SIR disease spread with combined non-sexual and sexual transmission routes


    Miller, Joel C.


    The emergence of diseases such as Zika and Ebola has highlighted the need to understand the role of sexual transmission in the spread of diseases with a primarily non-sexual transmission route. In this paper we develop a number of low-dimensional models which are appropriate for a range of assumptions for how a disease will spread if it has sexual transmission through a sexual contact network combined with some other transmission mechanism, such as direct contact or vectors. The equations der...

  3. of human immunodeficiency virus (HIV)

    African Journals Online (AJOL)

    Context: With increasing feminization of the human immunodeficiency virus (HIV) pandemic especially in Africa, more seropositive women are getting pregnant. There is therefore an increasing need for prevention of mother to child transmission (PMTCT) of HIV and increased need for awareness by our women. Objective: ...

  4. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

    NARCIS (Netherlands)

    Khanna, Reena; Bressler, Brian; Levesque, Barrett G.; Zou, Guangyong; Stitt, Larry W.; Greenberg, Gordon R.; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J.; Donner, Allan; Vandervoort, Margaret K.; Morris, Joan C.; Feagan, Brian G.; Anderson, Frank; Atkinson, Kenneth; Bacchus, Rahman; Berezny, Gary; Borthistle, Bruce; Buckley, Alan; Chiba, Naoki; Cockeram, Alan; Elkashab, Magdy; Fashir, Baroudi; Gray, James; Hemphill, Douglas; Hoare, Connie; Holland, Stephen; Hurowitz, Eric; Kaal, Nuri; Laflamme, Pierre; Borromee, Saint-Charles; Lau, Helena; McMullen, William; Memiche, Reshat; Menon, Krishna; Miller, D. Alexander; O'Hara, William; Oravec, Michael; Penner, Robert; Petrunia, Denis; Pluta, Henryk; Prabhu, Umesh; Prest, Marcia; Shaaban, Hani; Sheppard, Duane; Shulman, Scott; Somerton, Stephen; Wiesinger, Holly; Zandieh, Iman; Caenepeel, Philip; Claessens, Christophe; de Suray, Nicolas; andre, Jacques Defl; Holvoet, Jan; Vergauwe, Philippe


    Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of

  5. Disease Combinations Associated with Physical Activity Identified: The SMILE Cohort Study

    NARCIS (Netherlands)

    S. Dörenkamp (Sarah); I. Mesters (Ilse); J. Schepers (Jan); R. Vos (Rein); M. van den Akker (Marjan); J.A.W. Teijink (J. A W); R.A. de Bie (Robert)


    textabstractIn the search of predictors of inadequate physical activity, an investigation was conducted into the association between multimorbidity and physical activity (PA). So far the sum of diseases used as a measure of multimorbidity reveals an inverse association. How specific combinations of

  6. Combined osteotomy in patients with severe Legg-Calve-Perthes disease. (United States)

    Eamsobhana, Perajit; Kaewpornsawan, Kamolporn


    The purpose of the present study was to describe the clinical and radiographic results obtained with the combined osteotomy in patients with severe Legg-Calve-Perthes disease. During 2000 to 2010 patients with Legg-Calve-Perthes disease who intervened with combined osteotomy at Siriraj Hospital were evaluated. Clinical evaluation was categorized by Ratliff classification and radiographic evaluation was performed by Moss index, Lloyd Roberts classification and Stulberg classification. Twenty patients intervened with combined osteotomy. There were nineteen males and one female with a mean age of 7.7 years. The average follow-up was 49 months. Nine had a Catterall III and eleven had a Catterall IV. According to Herring classification, fourteen patients were Herring B and six were Herring C. In accordance with the Ratliff classification, the postoperative clinical results: fifteen good, three fair and two poor. According to Mose scale, eight patients had good results, nine had fair results and three had poor results. According to the Lloyd-Roberts classification eight patients had good results, nine had fair results and three had poor results. Based on the Stulberg classification, there were ten patients in class II, nine in class III and one in class V. The surgical treatment for severe Perthes disease with the best expected outcome is still a challenge. According to the results reported here, the combined osteotomy is safe and effective procedure for patients with severe Perthes disease in whom the femoral head cannot be contained by conventional forms of treatment.

  7. Evaluation of Clinical and Laboratory Data in Patients with Recurrent Infections and Suspected Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Hamid Ahanchian


    Full Text Available Background: Frequent infections is among the most frequent clinical dilemmas for primary care physicians. Immunodeficiency disorders are a heterogeneous group of illnesses that predispose patients to the recurrent infections, autoimmunity and malignancies. The aim of this study was to evaluate the clinical and laboratory data collected for the final diagnosis of patients referred with recurrent infections and suspected immunodeficiency to a local immunodeficiency clinic.   Methods: This epidemiological study was carried out between April 2010 and September 2012 at the Immunodeficiency Clinic of Mashhad. All patients with clinical manifestations of immunodeficiency who were referred to our clinic during this period of time were included in this study. 41 patients aged from 10 months to 51 years, were evaluated. Results: Forty one patients, aged between 10 months and 51 years were evaluated. Eleven patients had a primary immunodeficiency, four cases had a secondary immunodeficiency, in three patients an underlying structural disease were found, eight patients were predisposed to recurrent infections as a result of allergies and finally, fifteen cases were found to be normal individuals.   Discussion: Most patients with recurrent infection have a normal immune system. Allergic disorders are the most common predisposing factor to recurrent infection. However, as immunodeficiency disorders are potentially serious, early diagnosis can improve the quality of life and outcome and prevent severe sequels in future.

  8. Achieving Universal Access for Human Immunodeficiency Virus and Tuberculosis: Potential Prevention Impact of an Integrated Multi-Disease Prevention Campaign in Kenya

    Directory of Open Access Journals (Sweden)

    Reuben Granich


    Full Text Available In 2009, Government of Kenya with key stakeholders implemented an integrated multi-disease prevention campaign for water-borne diseases, malaria and HIV in Kisii District, Nyanza Province. The three day campaign, targeting 5000 people, included testing and counseling (HTC, condoms, long-lasting insecticide-treated bednets, and water filters. People with HIV were offered on-site CD4 cell counts, condoms, co-trimoxazole, and HIV clinic referral. We analysed the CD4 distributions from a district hospital cohort, campaign participants and from the 2007 Kenya Aids Indicator Survey (KAIS. Of the 5198 individuals participating in the campaign, all received HTC, 329 (6.3% tested positive, and 255 (5% were newly diagnosed (median CD4 cell count 536 cells/μL. The hospital cohort and KAIS results included 1,284 initial CD4 counts (median 348/L and 306 initial CD4 counts (median 550/μL, respectively (campaign and KAIS CD4 distributions P=0.346; hospital cohort distribution was lower P<0.001 and P<0.001. A Nyanza Province campaign strategy including ART <350 CD4 cell count could avert approximately 35,000 HIV infections and 1,240 TB cases annually. Community-based integrated public health campaigns could be a potential solution to reach universal access and Millennium Development Goals.

  9. Hematologic manifestations of feline immunodeficiency virus infection. (United States)

    Shelton, G H; Linenberger, M L; Grant, C K; Abkowitz, J L


    Studies were done on 53 cats with community-acquired infection with the feline immunodeficiency virus (FIV) to determine if hematologic abnormalities were comparable with those observed in patients seropositive for the human immunodeficiency virus (HIV). Nine cats were asymptomatic, 24 had clinical symptoms equivalent to AIDS-related complex (ARC), and 20 had AIDS-like disease. Hematologic abnormalities were detected in 75% (40 of 53) of FIV-seropositive cats, and multiple concurrent cytopenias were common. Anemia, lymphopenia, neutropenia, and thrombocytopenia occurred in 36%, 53%, 34%, and 8% of FIV-seropositive cats, respectively. Cytopenias were seen only in symptomatic (ARC or AIDS) cats. The occurrence of cytopenias and the distribution of clinical stages were similar in cats with concurrent feline leukemia virus (FeLV) infection and those with FIV alone, suggesting that these abnormalities were a direct consequence of FIV infection. In addition, abnormalities were noted in 72% of marrows from symptomatic cats and included hyperplasia of individual cell lineages and dysmorphic features. Our results demonstrate that the hematologic manifestations of FIV infection are strikingly similar to those reported in HIV-seropositive patients. Thus, FIV infection in cats is an excellent animal model to study the pathogenesis of blood and marrow abnormalities in AIDS, as well as to evaluate the hematologic toxicities of drug therapies.


    Directory of Open Access Journals (Sweden)

    A.Yu. Mushkin


    Full Text Available Initial immunodeficiencies are genetically conditioned defects of immune system; they are the basis for generalized infections including those induced by mycobacteria of tuberculosis complex. The lesions of skeleton in those patients are of different types depending on the kind of immunodeficiency. The article presents the results of clinical observation, conservative and surgical treatment of 12 children with mycobacterial lesions of skeleton on the ground different initial immunodeficiencies — severe combined immune deficiency, chronic granulematosis and insufficiency of interferon and interleukin 12.Key words: children, initial immunodeficiency, mycobacterial infection, bone lesions, surgical treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 60–64

  11. Tuberculose como doença definidora de síndrome da imunodeficiência adquirida: dez anos de evolução na Cidade do Rio de Janeiro Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Elizabeth Cristina Coelho Soares


    Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodeficiency Syndrome database from 1993 to 2002. RESULTS: The expanded definition of a case of acquired immunodeficiency syndrome, implemented in 1998, resulted in a substantial increase in the number of reported cases of acquired immunodeficiency syndrome, especially of those defined by immunologic criteria. Among the cases of acquired immunodeficiency syndrome defined only by disease, esophageal candidiasis, in its various forms, remained the most common opportunistic infection present at the time the cases of acquired immunodeficiency syndrome were reported. Although Pneumocystis carinii pneumonia was the second leading opportunistic infection in most of the years evaluated, it was surpassed by tuberculosis in 2001. CONCLUSION: Despite the decreased numbers of cases of acquired immunodeficiency syndrome defined by disease, tuberculosis remains a significant acquired immunodeficiency syndrome-defining event, currently more common than P. carinii pneumonia and toxoplasmosis. This is probably due to the high rate of tuberculosis prevalence in the city.

  12. Disease named entity recognition by combining conditional random fields and bidirectional recurrent neural networks (United States)

    Wei, Qikang; Chen, Tao; Xu, Ruifeng; He, Yulan; Gui, Lin


    The recognition of disease and chemical named entities in scientific articles is a very important subtask in information extraction in the biomedical domain. Due to the diversity and complexity of disease names, the recognition of named entities of diseases is rather tougher than those of chemical names. Although there are some remarkable chemical named entity recognition systems available online such as ChemSpot and tmChem, the publicly available recognition systems of disease named entities are rare. This article presents a system for disease named entity recognition (DNER) and normalization. First, two separate DNER models are developed. One is based on conditional random fields model with a rule-based post-processing module. The other one is based on the bidirectional recurrent neural networks. Then the named entities recognized by each of the DNER model are fed into a support vector machine classifier for combining results. Finally, each recognized disease named entity is normalized to a medical subject heading disease name by using a vector space model based method. Experimental results show that using 1000 PubMed abstracts for training, our proposed system achieves an F1-measure of 0.8428 at the mention level and 0.7804 at the concept level, respectively, on the testing data of the chemical-disease relation task in BioCreative V. Database URL: PMID:27777244

  13. Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review. (United States)

    Spyratos, Dionisios; Sichletidis, Lazaros


    Chronic obstructive pulmonary disease (COPD) is a common disease among the elderly that could be prevented by smoking cessation. As it is characterized by airflow limitation that is not fully reversible, bronchodilator therapy is the first choice of treatment. Symptomatic COPD patients with or without risk for future exacerbations have a strong indication for the permanent use of long- and ultralong-acting β2-agonists and/or long-acting muscarinic antagonists. Combining bronchodilators is an effective approach, as they demonstrate synergic action at a cellular level and have additive clinical benefits and fewer adverse events compared with increased doses of the monocomponents. Novel fixed-dose combinations of long-acting β2-agonists/long-acting muscarinic antagonists in one inhaler have been approved for clinical use by the US Food and Drug Administration and the European Medicines Agency. This review focuses on published clinical trials about the fixed-dose combination of umeclidinium/vilanterol trifenatate in patients with COPD. Results from six studies (five of them of 12 weeks' duration and one that lasted 1 year, including more than 6,000 patients in total) showed that umeclidinium/vilanterol trifenatate improved lung function, dyspnea, and health-related quality of life and decreased the exacerbation rate with no serious adverse events. More longstanding trials are needed to evaluate the effect of the drug on disease progression and compare it directly with other fixed-dose combinations.

  14. [Pulmonary complications in children with human immunodeficiency virus infection]. (United States)

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría


    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  15. Combined mitral and tricuspid valve repair in rheumatic valve disease: fewer reoperations with prosthetic ring annuloplasty. (United States)

    Bernal, José M; Pontón, Alejandro; Diaz, Begoña; Llorca, Javier; García, Iván; Sarralde, J Aurelio; Gutiérrez-Morlote, Jesús; Pérez-Negueruela, Carolina; Revuelta, José M


    We examined predictors of early and very long-term outcome after combined mitral and tricuspid valve repair for rheumatic disease. Between 1974 and 2002, 153 consecutive patients (mean age, 46.0+/-13.2 years) underwent combined mitral and tricuspid valve repair for rheumatic disease. Mitral disease was predominantly stenosis (82.3%); 100% of patients had organic tricuspid valve disease, predominantly with regurgitation (53.6%) or some degree of tricuspid stenosis (46.4%). Mitral repair included commissurotomy in 132 patients (86.3%) associated with a flexible annuloplasty in 108. Tricuspid valve repair included flexible annuloplasty in 68 patients (44.4%) and suture annuloplasty in 20 patients (13.1%) combined with tricuspid commissurotomy in 62 patients (42.5%). Thirty-day mortality was 5.9%. Late mortality was 60.1%. The median follow-up was 15.8 years (interquartile range, 6 to 19 years). Follow-up was 97.9% complete. Age>65 years was the only predictor of late mortality. Kaplan-Meier survival probability was 74.4% at 10 years and 57.0% at 15 years. Sixty-three patients required valve reoperation (mitral valve, 59; tricuspid valve, 38). Predictors of valve reoperations were either mitral or tricuspid commissurotomy without associated prosthetic ring annuloplasty. At 20 years, Kaplan-Meier freedom from reoperation was 48.5+/-5.1%. Combined mitral and tricuspid valve repair in rheumatic disease showed satisfactory early results. Long-term results were poor because of high mortality and a high number of valve-related reoperations. The use of prosthetic ring annuloplasty was significantly associated with a reduced incidence of both mitral and tricuspid valve reoperations.

  16. Optimal combinations of control strategies and cost-effective analysis for visceral leishmaniasis disease transmission.

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    Santanu Biswas

    Full Text Available Visceral leishmaniasis (VL is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis.

  17. [Drug combination characteristics of Shenxiong glucose injection in treating ischemic cerebrovascular disease in real world]. (United States)

    Wang, Gui-Qian; Xie, Yan-Ming; Liu, Huan; Zhang, Yin; Jia, Ping-Ping; Zhuang, Yan


    To analyze the clinical drug use characteristics of Shenxiong glucose injection in the treatment of ischemic cerebrovascular disease. From hospital information system (HIS) of 19 hospitals over China, the basic information of patients with Shenxiong glucose injection for ischemic cerebrovascular disease, traditional Chinese medicine and Western medicine diagnosis information, order information, and laboratory examination information were extracted. Then Apriori algorithm was used to construct the model, and the association analysis was performed by using Clementine 12 to analyze the clinical drug use characteristics of Shenxiong glucose injection in the real world. A total of 411 kinds of Western medicines and 110 kinds of traditional Chinese medicines were included in 784 cases of drug combination. In the drug combination, aspirin had the highest frequency in Western medicine, which was used in 515 cases (65.69%); Ginkgo biloba extract had the highest frequency in Chinese medicine, which was used in 121 cases (15.43%). Atorvastatin+aspirin (association rules of 10.15%) was the most common Western medicine pairs; atorvastatin+clopidogrel+aspirin (association support 5.56%) was the most common triple Western medicine therapy, often combined with antibiotics and blood stasis drugs in use. Results showed that Shenxiong glucose injection was often combined with antiplatelet drugs and blood stasis drugs in the treatment of ischemic cerebrovascular disease clinically, contributing to the enhancement of platelet aggregation and blood stasis. The incompatibility of combined application of drugs shall be noted to ensure the clinical medication safety and efficacy of the combined drug use. Copyright© by the Chinese Pharmaceutical Association.

  18. Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism. (United States)

    Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X


    Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

  19. [Evaluating an effectiveness of surgical treatment of gastroesophageal reflux disease combined with hiatal hernia]. (United States)

    Mozharovskiy, V V; Tsyganov, A A; Mozharovskiy, K V; Tarasov, A A

    To assess an effectiveness of surgical treatment of gastroesophageal reflux disease (GERD) combined with hiatal hernia (HH). The trial included 96 patients with GERD and HH who were divided into 2 groups. The principal difference between groups was the use of surgery in the main group and therapeutic treatment in the comparison group. The effectiveness of surgical treatment is superior to therapeutic treatment of GERD by more than 2.5 times. HH combined with GERD is an indication for surgical treatment. Fundoplication cuff should not lead to angular and rotational esophageal deformation. Nissen procedure in Donahue modification (Short Floppy Nissen) simulates optimally the geometry of esophago-gastric junction and His angle.

  20. Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease. (United States)

    Oertel, Markus F; Schüpbach, W Michael M; Ghika, Joseph-André; Stieglitz, Lennart H; Fiechter, Michael; Kaelin-Lang, Alain; Raabe, Andreas; Pollo, Claudio


    Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

  1. [The combined drug ascoril in the treatment of patients with chronic obstructive pulmonary disease concurrent with coronary heart disease]. (United States)

    Grigor'eva, N Iu; Kuznetsov, A N; Koroleva, T V; Koroleva, M E


    To evaluate the clinical efficacy of the combined drug ascoril (Glenmark, India) in patients with grade I-Ii chronic obstructive pulmonary disease (COPD) concurrent with coronary heart disease (CHD). Sixty patients, including 12 (20%) women and 48 (80%) men, aged 43 to 68 years (mean age 55.1 +9.9 years), with COPD were examined. The patients were divided into 2 groups. Group 1 used the combined broncholytic and expectorant drug ascoril and Group 2 took mucolytic agent ambroxol. The follow-up period was 7 days. On day 2 of ascoril treatment, all the patients showed a significant reduction in the intensity of cough that was completely relieved in 26 (87%) patients by treatment day 7. Prior to ascoril treatment, heart rate (HR) was 64.4+/-5.5 beats/min. A significant increase in HR to 72.7+/-10.1 beats/min was observed 20 min after the first drug intake (p < 0.05) and a decrease to 68.6+/-10.5 beats/min was seen after 60 min. On treatment day 7, HR was 63.0+/-6.5 beats/min, which was similar to that before ascoril treatment (p = 0.6). In the patients with COPD concurrent with CHD, the combined drug ascoril exerts broncholytic and expectorant effects, with no pronounced negative action on HR.

  2. Spatiotemporal analysis of tropical disease research combining Europe PMC and affiliation mapping web services. (United States)

    Palmblad, Magnus; Torvik, Vetle I


    Tropical medicine appeared as a distinct sub-discipline in the late nineteenth century, during a period of rapid European colonial expansion in Africa and Asia. After a dramatic drop after World War II, research on tropical diseases have received more attention and research funding in the twenty-first century. We used Apache Taverna to integrate Europe PMC and MapAffil web services, containing the spatiotemporal analysis workflow from a list of PubMed queries to a list of publication years and author affiliations geoparsed to latitudes and longitudes. The results could then be visualized in the Quantum Geographic Information System (QGIS). Our workflows automatically matched 253,277 affiliations to geographical coordinates for the first authors of 379,728 papers on tropical diseases in a single execution. The bibliometric analyses show how research output in tropical diseases follow major historical shifts in the twentieth century and renewed interest in and funding for tropical disease research in the twenty-first century. They show the effects of disease outbreaks, WHO eradication programs, vaccine developments, wars, refugee migrations, and peace treaties. Literature search and geoparsing web services can be combined in scientific workflows performing a complete spatiotemporal bibliometric analyses of research in tropical medicine. The workflows and datasets are freely available and can be used to reproduce or refine the analyses and test specific hypotheses or look into particular diseases or geographic regions. This work exceeds all previously published bibliometric analyses on tropical diseases in both scale and spatiotemporal range.

  3. Optimal combinations of acute phase proteins for detecting infectious disease in pigs

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Stockmarr, Anders; Piñeiro, Matilde


    gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative......The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect......, pigMAP, respectively. For the practical use of such combinations, methodology is described for establishing individual APP threshold values, above which, for any APP in the combination, ongoing infection/inflammation is indicated....

  4. Ethanol suppression of peripheral blood mononuclear cell trafficking across brain endothelial cells in immunodeficiency virus infection

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    Lola C Hudson


    Full Text Available Lola C Hudson1, Brenda A Colby1, Rick B Meeker21Department of Molecular Biosciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 2Department of Neurology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: Earlier studies suggested that the combination of alcohol use and immunodeficiency virus infection resulted in more severe neurologic disease than either condition individually. These deleterious interactions could be due to increased immune cell and virus trafficking or may result from interactions between ethanol and human immunodeficiency virus (HIV-associated toxicity within the brain. To determine the extent to which increased trafficking played a role, we examined the effect of ethanol on the migration of different peripheral blood mononuclear cell (PBMCs subsets across a brain endothelial cell monolayer. We utilized combinations of feline brain endothelial cells with astrocytes, and/or microglia with either acute exposure to 0.08 g/dL ethanol, a combination of ethanol and feline immunodeficiency virus (FIV, or FIV alone. Adherence of PBMCs to endothelium was increased in all combinations of cells with the addition of ethanol. Despite increased PBMC adhesion with ethanol treatment, transmigration of B cells, monocytes, CD4 T cells and CD8 T cells was not increased and was actually decreased in the presence of astrocytes. Expression of three common adhesion molecules, intercellular adhesion molecule-1 (ICAM1, ICAM2, and vascular cell adhesion molecule, was unchanged or slightly decreased by ethanol. This indicated that although adherence is increased by ethanol it is not due to an increased expression of adhesion molecules. RANTES, MIP1α, MIP1β, and MCP-1 mRNA expression was also studied in brain endothelial cells, astrocytes and microglia by reverse transcriptase-polymerase chain reaction. Ethanol treatment of astrocytes resulted in modest changes of

  5. Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil. (United States)

    Alvarez, X Antón; Cacabelos, R; Sampedro, C; Couceiro, V; Aleixandre, M; Vargas, M; Linares, C; Granizo, E; García-Fantini, M; Baurecht, W; Doppler, E; Moessler, H


    Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimer's disease (AD). We compared the safety and efficacy of the neurotrophic compound Cerebrolysin (10 ml; n=64), donepezil (10 mg; n=66) and a combination of both treatments (n=67) in mild-to-moderate (mini-mental state examination-MMSE score 12-25) probable AD patients enrolled in a randomized, double-blind trial. Primary endpoints were global outcome (Clinician's Interview-Based Impression of Change plus caregiver input; CIBIC+) and cognition (change from baseline in AD Assessment Scale-cognitive subscale+; ADAS-cog+) at week 28. Changes in functioning (AD Cooperative Study-Activities of Daily Living scale, ADCS-ADL) and behaviour (Neuropsychiatric Inventory, NPI) were secondary endpoints. Treatment effects in cognitive, functional and behavioral domains showed no significant group differences; whereas improvements in global outcome favored Cerebrolysin and the combination therapy. Cognitive performance improved in all treatment groups (mean±SD for Cerebrolysin: -1.7±7.5; donepezil: -1.2±6.1; combination: -2.3±6.0) with best scores in the combined therapy group at all study visits. Cerebrolysin was as effective as donepezil, and the combination of neurotrophic (Cerebrolysin) and cholinergic (donepezil) treatment was safe in mild-to-moderate AD. The convenience of exploring long-term synergistic effects of this combined therapy is suggested.

  6. Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review

    Directory of Open Access Journals (Sweden)

    Spyratos D


    Full Text Available Dionisios Spyratos, Lazaros Sichletidis Pulmonary Department, “G Papanikolaou” Hospital, Aristotle University of Thessaloniki, Exohi, Thessaloniki, Greece Abstract: Chronic obstructive pulmonary disease (COPD is a common disease among the elderly that could be prevented by smoking cessation. As it is characterized by airflow limitation that is not fully reversible, bronchodilator therapy is the first choice of treatment. Symptomatic COPD patients with or without risk for future exacerbations have a strong indication for the permanent use of long- and ultralong-acting ß2-agonists and/or long-acting muscarinic antagonists. Combining bronchodilators is an effective approach, as they demonstrate synergic action at a cellular level and have additive clinical benefits and fewer adverse events compared with increased doses of the monocomponents. Novel fixed-dose combinations of long-acting ß2-agonists/long-acting muscarinic antagonists in one inhaler have been approved for clinical use by the US Food and Drug Administration and the European Medicines Agency. This review focuses on published clinical trials about the fixed-dose combination of umeclidinium/vilanterol trifenatate in patients with COPD. Results from six studies (five of them of 12 weeks’ duration and one that lasted 1 year, including more than 6,000 patients in total showed that umeclidinium/vilanterol trifenatate improved lung function, dyspnea, and health-related quality of life and decreased the exacerbation rate with no serious adverse events. More longstanding trials are needed to evaluate the effect of the drug on disease progression and compare it directly with other fixed-dose combinations. Keywords: COPD treatment, bronchodilators, lung function, long-acting ß2-agonists, long-acting muscarinic receptor antagonist combination, umeclidinium/vilanterol

  7. BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Shrot, Shai; Soudack, Michalle [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Tel Aviv University, Sackler School of Medicine, Tel Aviv (Israel); Barkai, Galia [Sheba Medical Center, Pediatric Infectious Diseases Unit, Safra Children' s Hospital, Tel-Hashomer (Israel); Ben-Shlush, Aviva [Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel)


    When administered to an immune-compromised patient, BCG (Bacille Calmette-Guerin) can cause disseminated and life-threatening infections. To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. (orig.)

  8. Umeclidinium bromide and vilanterol in combination for the treatment of chronic obstructive pulmonary disease. (United States)

    Kelly, Emer


    Drugs from the two major classes of bronchodilator; umeclidinium, a long-acting muscarinic antagonist (LAMA), and vilanterol, a long-acting β2 agonist (LABA), have been combined in a single inhaler device for once-daily use in chronic obstructive pulmonary disease (COPD). These drugs have been proven safe and well tolerated in patients with COPD and show an enhanced improvement in FEV1 when compared to either drug in isolation and when compared with an established LAMA drug. In this article, we discuss the data supporting this combination inhaler and also review alternative combined LAMA/LABA options. We discuss where these agents are likely to find a place in the current therapy of COPD and where the future is likely to lead with these and other therapies.

  9. Detecting Diseases in Medical Prescriptions Using Data Mining Tools and Combining Techniques. (United States)

    Teimouri, Mehdi; Farzadfar, Farshad; Soudi Alamdari, Mahsa; Hashemi-Meshkini, Amir; Adibi Alamdari, Parisa; Rezaei-Darzi, Ehsan; Varmaghani, Mehdi; Zeynalabedini, Aysan


    Data about the prevalence of communicable and non-communicable diseases, as one of the most important categories of epidemiological data, is used for interpreting health status of communities. This study aims to calculate the prevalence of outpatient diseases through the characterization of outpatient prescriptions. The data used in this study is collected from 1412 prescriptions for various types of diseases from which we have focused on the identification of ten diseases. In this study, data mining tools are used to identify diseases for which prescriptions are written. In order to evaluate the performances of these methods, we compare the results with Naïve method. Then, combining methods are used to improve the results. Results showed that Support Vector Machine, with an accuracy of 95.32%, shows better performance than the other methods. The result of Naive method, with an accuracy of 67.71%, is 20% worse than Nearest Neighbor method which has the lowest level of accuracy among the other classification algorithms. The results indicate that the implementation of data mining algorithms resulted in a good performance in characterization of outpatient diseases. These results can help to choose appropriate methods for the classification of prescriptions in larger scales.

  10. Combined inguinal hernia in the elderly. Portraying the progression of hernia disease. (United States)

    Amato, Giuseppe; Agrusa, Antonino; Rodolico, Vito; Puleio, Roberto; Di Buono, Giuseppe; Amodeo, Silvia; Gulotta, Eliana; Romano, Giorgio


    Identification of a combined hernia is a common occurrence in the course of inguinal hernia repair. This type of protrusion disease seems to affect the elderly, in particular. Very few investigations have been carried out to ascertain the structural changes that occur in the groin affected by this clinical condition. Analysis of intraoperative findings of combined inguinal hernias evidenced in the elderly, from the most recent 100 groin hernia repair procedures carried out by a single operator, represents the basis of the article. Protrusions that presumably represent the forerunner of this type of hernia were also analyzed: double ipsilateral inguinal hernias composed of a direct and an indirect protrusion. The gross anatomical, as well as histological, modifications occurring during the development of combined protrusions were also evaluated. Combined hernia was the most frequent protrusion in patients over 65 years, accounting for 36% of the total in this patient group. In the same patient cohort, double inguinal hernia further involves 22% of elderly subjects. Macroscopically, progressive disruption of the inguinal back wall and degenerative reabsorption of the inferior epigastric vessels were evidenced. Histologically, inflammatory infiltrate, significant nerve and vascular injuries, along with severe muscle degeneration were recognized. The results seem to confirm that inguinal hernia is an unremitting progressive disease caused by chronic compressive structural damage. Combined hernias represent a frequent clinical condition in the elderly consequent to long-term degenerative damage. Therapy of combined protrusions must consider the impact of visceral vector forces. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  11. Combination of fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease. (United States)

    Bollmeier, Suzanne G; Prosser, Theresa R


    To evaluate the efficacy and safety of the combination of fluticasone furoate/vilanterol (FF/VI) and compare it with other inhaled combination corticosteroid/long-acting β₂-receptor agonists for maintenance treatment of chronic obstructive pulmonary disease (COPD). A PubMed and EMBASE search in June 2013 using the MeSH terms fluticasone and vilanterol identified trials using this combination for COPD. Additional information was gathered from references cited in the identified publications, the manufacturer, and package insert as well as the registry. Preference was given to randomized controlled clinical trials. Data from animal trials, clinical trials for asthma, and non-English sources were excluded. Given once daily, FF/VI improves trough forced expiratory volume at 1 s by about 230 mL in a 28-day trial versus placebo. However, a more modest increase (100-130 mL) was seen in 2 longer 28-week trials. In the longest trial of 1 year, a slight but significant decrease in the yearly rate of moderate plus severe exacerbations, the time to first moderate or severe exacerbation, and the frequency of exacerbations requiring systemic corticosteroids was seen. There was no difference in the rate of exacerbations requiring hospitalization. The product appears to have the adverse effect profile typical of its class. Of the inhaled corticosteroid/long-acting β₂ receptor agonist combinations, VI/FF is the first allowing once-daily dosing. Similar to the other combination products, it may slightly decrease the incidence of COPD exacerbations in the patient subset with Global Initiative for Chronic Obstructive Lung Disease risk category C or D. There are no direct safety or efficacy data comparing this with other available inhaled combination products. The once-daily dosing might improve adherence in select patients. The Ellipta delivery device may assist some who are unable to use other devices correctly.

  12. Treadmill training combined with water and land-based exercise programs: Effects on Parkinson's disease patients. (United States)

    Ayan, Carlos; Varela, Silvia; Vila, M Helena; Seijo-Martinez, Manuel; Cancela, José M


    There is a need for studies about the effects of treadmill training (TT) on Parkinson's disease (PD) patients when combined with other exercise training modalities. To identify the effects of a multicomponent rehabilitation program on the illness impact, quality of life and fitness level in Parkinson's disease. Participants were assigned to two exercise groups: water and land-based exercise (WL) or water and land-based exercise plus treadmill training (TWL). The water and land-based exercise group performed one water-based exercise and one land-based exercise session per week for 15 weeks. Participants in the water and land-based exercise plus treadmill training added two sessions of treadmill training to this schedule. The Senior Fitness Test (SFT) was used to assess the sample's fitness level. Participants in the water and land-based exercise Group experienced significant benefits in the disease impact (UPDRS t = 3.083; p = 0.029) and quality of life (PDQ-39 t = 2.942; p = 0.036). The addition of treadmill training did not have any significant effect on these variables. Both programs showed similar effects on the fitness components evaluated. Adding treadmill training to a combination of water and land-based exercise programs may have limited effects on quality of life and the impact on the disease.

  13. Combined genetic and imaging diagnosis for two large Chinese families affected with Pelizaeus-Merzbacher disease. (United States)

    Lv, Y; Cao, L H; Pang, H; Lu, L N; Li, J L; Fu, Y; Qi, S L; Luo, Y; Li-Ling, J


    Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder characterized by nystagmus, impaired motor development, ataxia, and progressive spasticity. Genetically defective or altered levels of proteolipid protein (PLP1) or gap-junction alpha protein 12 gene have been found to be a common cause. Here we report on two large Han Chinese families affected with this disease. The probands of both families had produced sons featuring cerebral palsy that had never been correctly diagnosed. PMD was suspected after careful analysis of family history and clinical features. Three rounds of molecular testing, including RT-PCR, genetics linkage and SRY sequence analyses, in combination with fetal ultrasound and magnetic resonance imaging, confirmed the diagnosis. In Family 1, in addition to two patients, three carriers were identified, including one who was not yet married. Genetic testing indicated that a fetus did not have the disease. A healthy girl was born later. In Family 2, two patients and two carriers were identified, while a fetus was genetically normal. A healthy girl was born later. We concluded that by combining genetic testing and imaging, awareness of the symptoms of PMD and understanding of its molecular biology, there is great benefit for families that are at risk for producing offspring affected with this severe disease.

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

    Directory of Open Access Journals (Sweden)

    Claire Rouzaud


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

  15. The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency. (United States)

    Dalm, Virgil A S H; Driessen, Gertjan J A; Barendregt, Barbara H; van Hagen, Petrus M; van der Burg, Mirjam


    Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency. To evaluate the presence of immunodeficiency in a series of 6 patients with JS. Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry. Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found. Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS.

  16. Pediatric Selective IgM Immunodeficiency

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    Marc F. Goldstein


    Full Text Available Objective. Limited information exists on features of pediatric Selective IgM immunodeficiency (SIgMID. Previously published pediatric cases and 2 new cases are reviewed. Methods. English literature from PubMed and references from relevant articles were reviewed. Previously reported cases and 2 new cases from an allergy/immunology practice were analyzed. Results. Forty-nine reported cases of SIgMID presented with respiratory infections (77.6%, gastrointestinal disease (16.3%, skin disease (12.2%, and meningitis (8.2%. Mean serum IgM level was 16.5±13.8 mg/dL. Two patients were identified with SIgMID among 6300 active pediatric patients (0.03% presenting with asthma, vasomotor rhinitis, and recurrent respiratory infections. In the 51 cases reported, none developed lymphoproliferative disease nor evolved into panhypogammaglobulinemia; four fatalities were reported. Conclusions. The prevalence of SIgMID in our pediatric population was 0.03%. In general, respiratory infections are the common comorbid conditions. Death and autoimmune disease are uncommon complications of pediatric SIgMID.

  17. Primary immunodeficiency leading to mycobacterial disease

    Directory of Open Access Journals (Sweden)

    Esther van de Vosse


    To facilitate the analysis of variations identified by researchers around the world, databases have been set up that contain all reported MSMD patients and mutations (see for instance: Thus far, just over 400 patients have been reported worldwide with MSMD and this is probably only the tip of the iceberg. Also, other genes are still expected to be found to cause MSMD; no genes have been reported so far in which mutations specifically lead to susceptibility to tuberculosis.

  18. Pulmonary malakoplakia associated with immunodeficiency by HTLV-1 and HIV

    Directory of Open Access Journals (Sweden)

    Manuela Madruga


    Full Text Available Malakoplakia is a rare chronic inflammatory disease often confused with neoplasia. In this paper we report two cases of pulmonary Malakoplakia, both with typical clinical diagnosis of tuberculosis and lung cancer. A patient with human T-lymphotropic virus type I (HTLV-1 and diagnosis of adult T-cell leukemia/lymphoma, and another patient with human immunodeficiency virus (HIV, which was treated for tuberculosis, but, after pulmonary lobectomy, was evidenced Rodococosis equi, progressed to death.

  19. Feline immunodeficiency. ABCD guidelines on prevention and management. (United States)

    Hosie, Margaret J; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C


    Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the 'gold standard' laboratory test for FIV serology. PCR-based assays vary in performance. Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats

  20. Combined influence of multiple climatic factors on the incidence of bacterial foodborne diseases. (United States)

    Park, Myoung Su; Park, Ki Hwan; Bahk, Gyung Jin


    Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (Psnowfall, wind speed, duration of sunshine, and cloudiness were not significant for these 3 FBD. Other FBD, including campylobacteriosis, were not significantly associated with any combination of climatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease. (United States)

    Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya


    An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease. Copyright © 2014 the American Physiological Society.

  2. Effects of sanxuemingmu capsule combined with compound anisoine in ocular ischemic diseases

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    Jian-Chao Li


    Full Text Available AIM: To evaluate the effects of sanxuemingmu capsule combined with compound anisoine in the ocular ischemic disease.METHODS: We divided our patient into two groups according to their blood-activating and stasis-dissolving drug using history at first, then divided them into observation/positive/negative control subgroups according to random case-control method. The clinical key data and advert effects after 3 cycles of treatment were obtained by visual acuity/visual field and color Doppler.RESULTS: The index of general effects/visual acuity/the general visual acuity loss/the artery/vein perfusion time of fundus fluorescein angiography(FFAand color Doppler index(CDItogether with the advert effects rate of cardiovascular system of the observation groups were significantly better than those of the contrast groups.CONCLUSION: The combination of sanxuemingmu capsule with anisoine is effective in the ocular ischemic diseases and can lessen the cardiovascular advert effect rate of ocular ischemic diseases suffer while this administration method is more benefit in cases without blood-activating and stasis-dissolving drug using history than cases with drug using cases.

  3. [Fast track surgery combined with laparoscopy in the treatment of infant Hirschsprung disease]. (United States)

    Tang, Weibing; Geng, Qiming; Zhang, Jie; Chen, Huan; Lyu, Xiaofeng; Lu, Changgui; Jiang, Weiwei; Li, Wei; Li, Bo; Xu, Xiaoqun


    To evaluate the safety and efficacy of fast track surgery (FTS) combined with laparoscopy in the treatment of infant Hirschsprung disease. Clinical data of 72 infants with Hirschsprung disease undergoing elective pull-through surgery from June 2010 to June 2013 were retrospectively summarized. The patients were divided into two groups: fast track surgery combined with laparoscopy group (FTS group, n=33) and laparoscopic surgery with traditional management perioperatively (control group, n=39). Postoperative intestinal function recovery, hospital stay, cost of hospitalization, complications were compared and postoperative recovery was followed-up for four weeks. There were no significant differences in intraoperative blood loss and operative time between FTS and control group (both P>0.05). The recovery of bowel movement was earlier in the FTS group but the difference was not statistically significant (P=0.078). The hospital stay was shorter [(10 ± 2) d vs. (14 ± 4) d] and cost of hospitalization was lower [(15 316 ± 2273) Yuan vs. (18 641 ± 3082) Yuan] in FTS group than those in control group(PHirschsprung disease is safe and effective.

  4. Radial Artery Fascial Flow-Through Free Flap for Combined Revascularization in Moyamoya Disease. (United States)

    Russin, Jonathan; Carey, Joseph


    Free flaps are commonly used by other surgical subspecialties for soft tissue reconstruction and revascularization. Cranial applications of these flaps have been limited to only a single case report. To present a new technique for combined revascularization in moyamoya disease using a flow-through free flap. Data were obtained from an Institutional Review Board-approved, prospectively maintained database with informed consent from the patient. A 28-yr-old patient presented with progressive stenosis of the proximal anterior cerebral artery resulting in ischemic infarcts. Direct revascularization of the anterior cerebral artery territory and indirect revascularization of the middle cerebral artery with a large vascularized fascial pedicle was performed. Flow-through free flaps offer a unique combination of revascularization and a large vascularized pedicle. This technique highlights the application of these flaps for revascularization in moyamoya disease and the value of multidisciplinary collaboration. Revascularization will likely play an increasing role in the open surgical treatment of cerebrovascular disease. We believe that flow-through free flaps will be a contribution to the future of revascularization in neurosurgery.

  5. Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots. (United States)

    la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Malvagia, Sabrina; Funghini, Silvia; Moriondo, Maria; Valleriani, Claudia; Lippi, Francesca; Ombrone, Daniela; Della Bona, Maria Luisa; Speckmann, Carsten; Borte, Stephan; Brodszki, Nicholas; Gennery, Andrew R; Weinacht, Katja; Celmeli, Fatih; Pagel, Julia; de Martino, Maurizio; Guerrini, Renzo; Wittkowski, Helmut; Santisteban, Ines; Bali, Pawan; Ikinciogullari, Aydan; Hershfield, Michael; Notarangelo, Luigi D; Resti, Massimo; Azzari, Chiara


    Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program. This study evaluate whether mass spectrometry can identify metabolite abnormalities in dried blood spots (DBSs) from affected patients, with the final goal of individuating the disease at birth during routine newborn screening. DBS samples from 9 patients with genetically confirmed PNP-combined immunodeficiency, 10,000 DBS samples from healthy newborns, and 240 DBSs from healthy donors of different age ranges were examined. Inosine, dIno, guanosine, and dGuo were tested by using tandem mass spectrometry (TMS). T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) levels were evaluated by using quantitative RT-PCR only for the 2 patients (patients 8 and 9) whose neonatal DBSs were available. Mean levels of guanosine, inosine, dGuo, and dIno were 4.4, 133.3, 3.6, and 3.8 μmol/L, respectively, in affected patients. No indeterminate or false-positive results were found. In patient 8 TREC levels were borderline and KREC levels were abnormal; in patient 9 TRECs were undetectable, whereas KREC levels were normal. TMS is a valid method for diagnosis of PNP deficiency on DBSs of affected patients at a negligible cost. TMS identifies newborns with PNP deficiency, whereas TREC or KREC measurement alone can fail. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  6. Estimating the causal effects of chronic disease combinations on 30-day hospital readmissions based on observational Medicaid data. (United States)

    Casucci, Sabrina; Lin, Li; Hewner, Sharon; Nikolaev, Alexander


    Demonstrate how observational causal inference methods can generate insights into the impact of chronic disease combinations on patients' 30-day hospital readmissions. Causal effect estimation was used to quantify the impact of each risk factor scenario (ie, chronic disease combination) associated with chronic kidney disease and heart failure (HF) for adult Medicaid beneficiaries with initial hospitalizations in 2 New York State counties. The experimental protocol: (1) created matched risk factor and comparator groups, (2) assessed covariate balance in the matched groups, and (3) estimated causal effects and their statistical significance. Causality lattices summarized the impact of chronic disease comorbidities on readmissions. Chronic disease combinations were ordered with respect to their causal impact on readmissions. Of disease combinations associated with HF, the combination of HF, coronary artery disease, and tobacco abuse (in that order) had the highest causal effect on readmission rate (+22.3%); of disease combinations associated with chronic kidney disease, the combination of chronic kidney disease, coronary artery disease, and diabetes had the highest effect (+9.5%). Multi-hypothesis causal analysis reveals the effects of chronic disease comorbidities on health outcomes. Understanding these effects will guide the development of health care programs that address unique care needs of different patient subpopulations. Additionally, these insights bring new attention to individuals at high risk for readmission based on chronic disease comorbidities, allowing for more personalized attention and prioritization of care. Multi-hypothesis causal analysis, a new methodological tool, generates meaningful insights from health care claims data, guiding the design of care and intervention programs.

  7. Autoimmune Cytopenias In Common Variable Immunodeficiency (CVID

    Directory of Open Access Journals (Sweden)

    Roshini Sarah Abraham


    Full Text Available Common variable immunodeficiency (CVID is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%(Chapel et al., 2008;Cunningham-Rundles, 2008, autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004;Chapel et al., 2008 of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia and neutropenia. While it may seem paradoxical prima facie that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.

  8. Specific role of combination aclidinium: formoterol in the treatment of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Matera MG


    Full Text Available Maria Gabriella Matera,1 Alessandro Sanduzzi,2 Mario Cazzola3 1Department of Experimental Medicine, Second University of Naples, 2Department of Respiratory Diseases, Monaldi Hospital, University Federico II, Naples, 3Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy Abstract: Co-administration of a long-acting β2-agonist and a long acting muscarinic antagonist produces superior bronchodilation compared with their individual effects. Our preclinical data indicated that combining aclidinium bromide (ACLI and formoterol fumarate (FORM provides synergistic benefit on smooth muscle relaxation of both large and small human airways. Data from more than 2,000 patients in eleven clinical trials documented that ACLI/FORM, a twice-daily fixed-dose combination, produces a greater degree of bronchodilation than ACLI or FORM monotherapy alone and is safe and well tolerated. Two large key trials have shown that there is a benefit in using ACLI/FORM when the clinical target is the variability of symptoms and mainly nighttime and/or early morning symptoms. ACLI/FORM is the only long acting muscarinic antagonist/long acting β2-agonist fixed-dose combination that has been studied for this therapeutic indication. Keywords: aclidinium, formoterol, fixed-dose combination, COPD, symptoms

  9. Infections and immunodeficiency in Down syndrome. (United States)

    Ram, G; Chinen, J


    Down syndrome (DS) is the most common genetic disease and presents with cognitive impairment, cardiac and gastrointestinal abnormalities, in addition to other miscellaneous clinical conditions. DS individuals may have a high frequency of infections, usually of the upper respiratory tract, characterized by increased severity and prolonged course of disease, which are partially attributed to defects of the immune system. The abnormalities of the immune system associated with DS include: mild to moderate T and B cell lymphopenia, with marked decrease of naive lymphocytes, impaired mitogen-induced T cell proliferation, reduced specific antibody responses to immunizations and defects of neutrophil chemotaxis. Limited evidence of genetic abnormalities secondary to trisomy of chromosome 21 and affecting the immune system is available, such as the potential consequences of gene over-expression, most significantly SOD1 and RCAN1. Secondary immunodeficiency due to metabolic or nutritional factors in DS, particularly zinc deficiency, has been postulated. Non-immunological factors, including abnormal anatomical structures (e.g. small ear canal, tracheomalacia) and gastro-oesophageal reflux, may play a role in the increased frequency of respiratory tract infections. The molecular mechanisms leading to the immune defects observed in DS individuals and the contribution of these immunological abnormalities to the increased risk of infections require further investigation. Addressing immunological and non-immunological factors involved in the pathogenesis of infectious diseases may reduce the susceptibility to infections in DS subjects. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  10. Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

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    Monique E. Francois


    Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

  11. Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease. (United States)

    Ramadan, Wijdan H; Kabbara, Wissam K; El Khoury, Ghada M; Al Assir, Sarah A


    Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

  12. Histoplasmosis in Patients With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) (United States)

    Anderson, Albert M.; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W.; Jhaveri, Malhar; Greenberg, Richard N.; Bamberger, David M.; Rodgers, Mark; Crawford, Timothy N.; Wheat, L. Joseph


    Abstract Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p 150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis. PMID:24378739

  13. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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    Villegas VM


    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  14. [The algorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus]. (United States)

    Gurov, A V; Biryukova, E V; Yushkina, M A


    The objective of the present study was to determine the leading clinical and pathogenetic factors determining the clinical course of the pyoinflammatory ENT diseases in the patients with diabetes mellitus (DM) and to develop the algorithm for the rational therapy of these conditions. A total of 145 patients presenting with pyoinflammatory ENT diseases and concomitant diabetes mellitus were available for the examination that included the microbiological and biochemical studies, determination of the total lipid spectrum, glycated hemoglobin (HbA1c) level, and glycemic profile. Also, the body mass index of the patients was estimated along with the type and severity of obesity. Moreover, the character of antibacterial and hypoglycemic therapy was evaluated. The mathematical analysis of the data obtained revealed the clinical and biochemical parameters determining the clinical picture of the pyoinflammatory ENT diseases in the patients with diabetes mellitus. These were localization of the pyogenic process in the larynx, abdominal obesity, fasting hyperglycemia in excess of 8.3 mmol/l, and dyslipidemia accompanied by the reduction in the amount of high density lipoproteins to below 40 mg/100 ml and the increase of low density lipoproteins to above 155 mg/100 ml. The results of the study were used to develop the differentialalgorithm for the combined treatment of pyoinflammatory ENT diseases in the patients with diabetes mellitus based on the proposed original scale for the prediction of pyogenic complications.

  15. Combined scintigraphic and radiographic diagnosis of bone and joint diseases. 3. rev. and enl. ed.

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    Bahk, Yong-Whee [Sung Ae General Hospital, Seoul (Korea). Dept. of Nuclear Medicine and Radiology


    The third edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases has been comprehensively rewritten and rearranged. It now encompasses, in addition to the bone and joint diseases described in the two earlier editions, hitherto unpublished novel applications of pinhole scanning to the diagnosis of a broader spectrum of skeletal disorders than ever before, including those of the soft tissues. A large number of state-of-the-art scans and corroboratory images obtained using CT, MRI and/or sonography are presented side by side. The book has been considerably expanded to discuss five new themes: Normal Variants and Artifacts, Drug-Induced Osteoporosis, Soft-Tissue Tumors and Tumor-like Conditions, PET/CT in Bone and Joint Diseases and A Genetic Consideration of Skeletal Disorders. Topical chapters on rheumatic skeletal disorders, malignant tumors of bone, benign tumors of bone and traumatic diseases have also been thoroughly rewritten and are complemented by the addition of some 90 recently acquired cases. (orig.)

  16. Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

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    Julie Harvengt


    Full Text Available A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She was treated by enzyme replacement therapy (ERT. Clinical follow-up showed mild developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical studies revealed multiple respiratory chain deficiencies and a mosaic pattern of deficient complex IV immunostaining in liver and fibroblast. Molecular analysis identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation in MPV17. A younger sister unaffected by mtDNA depletion, presented with pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral normalization without any neurological symptom. A third sister, affected by both conditions, had marked developmental delay, strabismus and ophthalmoplegia but no liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related disease. The combined pathological effect of Gaucher and mitochondrial diseases can negatively impact neurological and liver functions and influence the outcome in consanguineous families. The immunocytochemical staining of OXPHOS protein in tissues and cultured cells is a powerful tool revealing mosaic pattern of deficiency pointing to mtDNA-related mitochondrial disorders.


    African Journals Online (AJOL)

    INTRODUCTION. An estimated 42 million people worldwide are now infected with the human immunodeficiency virus. (HIV), (1) the causative agent of the acquired immunodeficiency syndrome compared with. 30million people that were infected in 1997(2). Ninety per cent (90%) of these live in developing countries.

  18. Post exposure prophylaxis against human immunodeficiency virus ...

    African Journals Online (AJOL)


    Nov 23, 2015 ... immunodeficiency virus post ex- posure prophylaxis (HIV PEP) among paediatricians in Nigeria. ... pathogens including human immunodeficiency virus. (HIV) during the course of providing care for their pa- tients. ..... Ford N, Shubber Z, Calmy A,. Irvine C, Rapparini C, Ajose O, et al. Choice of antiretroviral ...

  19. Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency

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    Kathryn Victoria Whitmore


    Full Text Available Adenosine deaminase (ADA deficiency is best known as a form of severe combined immunodeficiency (SCID which results from mutations in the gene encoding adenosine deaminase. Affected patients present with clinical and immunological manifestations typical of a severe combined immunodeficiency. Therapies are currently available that can that target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidence that deficiency of ADA has significant impact on non-immunological organ systems. This review will outline the impact of ADA deficiency on various organ systems, starting with the well understood immunological abnormalities. We will discuss possible pathogenic mechanisms and also highlight ways in which current treatments could be improved. In doing so, we aim to present ADA deficiency as more than an immunodeficiency and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems. Only by fully understanding ADA deficiency and its manifestations in all organ systems can we aim to deliver therapies that will correct all the clinical consequences.

  20. Combining carotid intima-media thickness with carotid plaque on screening for coronary heart disease. (United States)

    Wald, David S; Bestwick, Jonathan P; Morton, Geraint; Drummond, Linda; Jenkins, Nick; Khodabakhsh, Pouran; Curzen, Nick P


    Ultrasound-detected carotid artery intima-media thickness (IMT) and carotid plaque are possible screening tests for coronary heart disease (CHD) among asymptomatic individuals. To assess the increase in screening performance of combining carotid IMT and plaque compared with each measurement alone in the identification of individuals with CHD. Ultrasound examination of left and right carotid arteries was performed on 100 individuals (median age 57), 55 with a history of CHD (unstable angina or myocardial infarction) and 45 without. IMT measurements were taken from the common carotid artery and plaque was identified above, at and below the carotid bifurcation. Associations between IMT and plaque were determined using logistic regression, and screening performance was assessed from the distributions of IMT and plaque among cases and controls. At a false-positive rate of 5%, IMT (cut-off >0.75 mm) identified 30% (95% CI 14-58) of affected individuals. There was an increase in the detection rate of 8 percentage points (1-33%) using IMT and plaque combined compared with IMT alone. As the false-positive increased, the difference in the detection rate increased, up to a maximum of 20 percentage points (5-38%) at a false-positive rate of 20%. The comparison of IMT and plaque combined with plaque alone could only be estimated for the false-positive rate observed using plaque alone (18%); at this point the detection rate was 72% for plaque and 75% for plaque and IMT combined, an increase of 3 percentage points (0-4%). In screening for CHD, combining carotid IMT measurement with plaque assessment is better than using either measurement alone, but the improvement in discrimination is not sufficient to make carotid ultrasound screening for CHD worthwhile.

  1. [Clinical study of non-alcoholic fatty liver disease and its combined the chronic HBV infection]. (United States)

    He, J; Zeng, Y L; Li, W; Guo, E E; Li, J L; Kang, Y; Shang, J


    Objective: to compared with clinical data between nonalcoholic fatty liver disease (NAFLD) and Chronic HBV infection with NAFLD, and to explore the relationship between HBV infection and hepatic steatosis. Methods: A total of 81 patients with clinical data in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to June 2016 were enrolled and divided into NAFLD group and HBV combined NAFLD group.Comparison of The levels of liver function (ALT, AST, ALP, GGT), blood lipid (TC, TG, HDL, LDL), blood glucose (GLU), uric acid (UA), hepatic fibrosis (S) and inflammation (G) And hepatic steatosis (F), and to explore the relationship between HBV infection and hepatic steatosis. The independent samples t-test or Wilcoxon two -sample test was used for comparison of continuous data,and the chi-square test was used for comparison of categorical data. Multinomial Logistic regression was used to analyze The risk factors of hepatic steatosis, P HBV with NAFLD group. Baseline level comparison: ALT (t = -4.379, P HBV infection-related indicators, it is difficult to distinguish between NAFLD and NAFLD combined with HBV differences; HBV infection and hepatic steatosis have a certain relationship.

  2. Disease: H01264 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01264 Hepatic venoocclusive disease with immunodeficiency (VODI) Hepatic venoocclusive disea...ound to be associated with VODI. Immune system disease; Liver disease SP110 [HSA:...are associated with immunodeficiency and hepatic veno-occlusive disease. Nat Genet 38:620-2 (2006) ...

  3. [A case of acquired immunodeficiency syndrome with ileocecal ulcer]. (United States)

    Iwasaki, Tetsuyoshi; Saruta, Masayuki; Sawada, Ryoichi; Ide, Daisuke; Arihiro, Seiji; Matsuoka, Mika; Katoh, Tomohiro; Tajiri, Hisao


    We report a case of a patient with acquired immunodeficiency syndrome (AIDS) and ileocecal ulcer. A 31-year-old man was admitted with chief complaints of decreased body weight and abdominal pain. Colonoscopy revealed a round punched-out ulcer on the ileocecal valve. Initially, we suspected entero-Behçet's disease and simple ulcer as the cause of the ileocecal ulcer. However, after histologic examination of tissue biopsies obtained during colonoscopy, we diagnosed the patient as having cytomegalovirus (CMV) enteritis. Based on the patient's white blood cell depletion and CMV enteritis, we performed a human immunodeficiency virus (HIV) antibody test. The test was positive, and the diagnosis of AIDS was established. The number of patients with AIDS has been increasing in Japan; thus, we should consider the possibility of CMV enteritis and AIDS in young adult patients affected by ileocecal ulcer with no notable history.

  4. New insights into Alzheimer's disease progression: a combined TMS and structural MRI study.

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    Eini Niskanen

    Full Text Available BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas. METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD and mild cognitive impairment (MCI patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness. CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.

  5. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

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    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)


    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  6. A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management

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    Mansueto Gomes Neto

    Full Text Available INTRODUCTION: In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE: To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS: We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT: The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION: Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk

  7. Combination of dynamic (11)C-PIB PET and structural MRI improves diagnosis of Alzheimer's disease. (United States)

    Liu, Linwen; Fu, Liping; Zhang, Xi; Zhang, Jinming; Zhang, Xiaojun; Xu, Baixuan; Tian, Jiahe; Fan, Yong


    Structural magnetic resonance imaging (sMRI) is an established technique for measuring brain atrophy, and dynamic positron emission tomography with (11)C-Pittsburgh compound B ((11)C-PIB PET) has the potential to provide both perfusion and amyloid deposition information. It remains unclear, however, how to better combine perfusion, amyloid deposition and morphological information extracted from dynamic (11)C-PIB PET and sMRI with the goal of improving the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We adopted a linear sparse support vector machine to build classifiers for distinguishing AD and MCI subjects from cognitively normal (CN) subjects based on different combinations of regional measures extracted from imaging data, including perfusion and amyloid deposition information extracted from early and late frames of (11)C-PIB separately, and gray matter volumetric information extracted from sMRI data. The experimental results demonstrated that the classifier built upon the combination of imaging measures extracted from early and late frames of (11)C-PIB as well as sMRI achieved the highest classification accuracy in both classification studies of AD (100%) and MCI (85%), indicating that multimodality information could aid in the diagnosis of AD and MCI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Corticosteroids and adrenoceptor agonists: the compliments for combination therapy in chronic airways diseases. (United States)

    Sin, Don D; Man, S F Paul


    The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.

  9. Prostatome: A combined anatomical and disease based MRI atlas of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Rusu, Mirabela; Madabhushi, Anant, E-mail: [Case Western Reserve University, Cleveland, Ohio 44106 (United States); Bloch, B. Nicolas; Jaffe, Carl C. [Boston University School of Medicine, Boston, Massachusetts 02118 (United States); Genega, Elizabeth M. [Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215 (United States); Lenkinski, Robert E.; Rofsky, Neil M. [UT Southwestern Medical Center, Dallas, Texas 75235 (United States); Feleppa, Ernest [Riverside Research Institute, New York, New York 10038 (United States)


    Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework

  10. Combined treatment of periodontal disease and benign mucous membrane pemphigoid. Case report with 8 years maintenance. (United States)

    Damoulis, P D; Gagari, E


    Desquamative gingivitis may be the clinical manifestation of one of several systemic diseases. The clinical course of the disease can be complicated by plaque-associated periodontitis. However, there is no information currently available for the concurrent management of both conditions. This paper presents the treatment and 8-year maintenance of a patient with periodontal disease and benign mucous membrane pemphigoid (BMMP). The first phase of treatment included oral hygiene instructions and local corticosteroid administration, followed by scaling and root planing. The patient's compliance and excellent response to therapy allowed for subsequent surgical pocket elimination and augmentation of the zone of keratinized tissue for prosthetic reasons. Over the following 8 years, the patient's periodontal condition remained stable even though periodontal maintenance was erratic. For the control of BMMP, intermittent administration of corticosteroids was necessary, without any significant local or systemic side effects. We suggest that combined treatment and long-term maintenance of BMMP and periodontitis are feasible under certain conditions and propose a clinical protocol for treatment which could serve as a guideline for similar conditions.

  11. Monitoring hand, foot and mouth disease by combining search engine query data and meteorological factors. (United States)

    Huang, Da-Cang; Wang, Jin-Feng


    Hand, foot and mouth disease (HFMD) has been recognized as a significant public health threat and poses a tremendous challenge to disease control departments. To date, the relationship between meteorological factors and HFMD has been documented, and public interest of disease has been proven to be trackable from the Internet. However, no study has explored the combination of these two factors in the monitoring of HFMD. Therefore, the main aim of this study was to develop an effective monitoring model of HFMD in Guangzhou, China by utilizing historical HFMD cases, Internet-based search engine query data and meteorological factors. To this end, a case study was conducted in Guangzhou, using a network-based generalized additive model (GAM) including all factors related to HFMD. Three other models were also constructed using some of the variables for comparison. The results suggested that the model showed the best estimating ability when considering all of the related factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. [Lopinavir/ritonavir in human immunodeficiency virus-infected women]. (United States)

    Téllez, María Jesús


    There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Dermatophytosis And Human Immunodeficiency Virus(HIV Infection

    Directory of Open Access Journals (Sweden)

    Sentamilselvi G


    Full Text Available The incidence of Human Immunodeficiency Virus (HIV antibody through Enzyme Linked Immunosorbant Assay (ELISA technique was observed to be 2.5% among the 200 patients with dermatophytosis. The incidence was less (1% in those with chronic disease compared to those with nonchronic disease (4%. The positivity seemed to be more in females screened. The clinical presentation of dermatophytosis in HIV positive patients was similar to that screen in general population. Trichophyton rubrum was the commonest isolate. Unusual widespread lesions and atypical lesions of nails like proximal subungual white onychomycosis were not encountered in the present series.

  14. Nondrug therapy in the combination rehabilitation of patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    V. L. Golubev


    Full Text Available Non-drug rehabilitation in Parkinson’s disease (PD has recently attracted the increasing attention of neurologists worldwide. Symptomatic medical treatment only prolongs the period of relative wellbeing and little affects the course of the disease, without preventing its progression. Today this raises the question of whether other or additional therapeutic approaches to rehabilitating patients with this disease should be sought. The elaboration and practical implementation of a program for multidisciplinary patient rehabilitation are most effective to date. This program includes combination therapy based on the use of current drugs and different variants of nondrug therapy. Within the current concept of medical treatment for PD, there are two strategic approaches: 1 to search for agents that are able to slow, delay, or stop its progression (the so-called neuroprotection and 2 to develop more effective symptomatic therapies. The latter approach is presently considered to be basic. At large, more than 40-year experience in using dopaminergic and other antiparkinsonian agents indicates that this therapy cannot drastically solve the problem of PD treatment. So nondrug care methods whose improvement has become a relevant task of current therapeutic strategy in this disease are the focus of attention today. A nonpharmacological approach to treating PD is appropriate at all its stages. Here are just some of these methods: medicinal vacation, phototherapy, sleep deprivation, electroconvulsive therapy, and transcranial magnetic stimulation. Patients’ compliance to dietary advice is of significance. The experience shows that the most accessible and efficient and safe nondrug treatment is of course a package of measures to stimulateand restore a patient’s physical activity, which encompasses special functional training programs, kinesitherapy, multisensory training,physical exercises, etc. There is a need to further accumulate experience

  15. Relationship of emotional intelligence and adherence to combination antiretroviral medications by individuals living with HIV disease. (United States)

    Willard, Suzanne


    Medications are an intentional and purposeful means to the successful management of many chronic diseases. In the treatment of disease caused by HIV, adherence to medication is of particular concern because any level of nonadherence, often a few missed doses, will lead eventually to the development of drug resistance. Many predictors of poor adherence to HIV medications have been identified as significant factors in adherence. Among these is the emotional aspect. The purpose of this study was to examine emotional intelligence (EI) and adherence to combination antiretroviral therapy in individuals who are infected with HIV. EI is defined as the ability to perceive and express emotions, facilitate emotions, understand and reason with emotion, and manage emotions. EI has been correlated with various aspects of success in life. In this study, EI was measured by the Mayer, Salovey, Caruso Emotional Intelligence Test. Adherence to medications was measured by self-report and defined as less than 10% missed doses of medications. Eighty-two participants were recruited from an urban hospital-based HIV clinic. Pearson's r was used to analyze the data for significance, and no correlation was reported. This data set was not large enough to prove significance, statistically, of the research question. However, an unexpected result of this study was that the overall EI scores for this particular population were markedly lower than the test norms. Further study would be warranted and recommended to explore El measurement in people at risk for HIV disease or in those who have the disease to further understand the impact of emotions and EI in this specific population.

  16. A genetic risk score combining ten psoriasis risk loci improves disease prediction.

    Directory of Open Access Journals (Sweden)

    Haoyan Chen


    Full Text Available Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS and a weighted (wGRS approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7 versus 12.09 (SD 1.8, p = 4.577×10(-40. The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57, p = 2.010×10(-65. To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC. The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p = 2.13×10(-8. Additionally, the AUC for HLA-C alone (rs10484554 was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p = 0.18, highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p = 4.91×10(-6 and family history (p = 0.020. Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.

  17. Unilateral and bilateral lumbosacral transitional vertebrae : comparison of the incidence of combined diseases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Yong; Kwon, Soon Tae; Han, Tae Il; Lee, Se Hyo; Han, Ki Tae; An, Jae Sung; Yang, Jun Young; Lee, Jun Kyu [College of Medicine, Chungnam National University, Taejon (Korea, Republic of); Kim, Hyun Jeong [Eulji College of Medicine, Taejon (Korea, Republic of)


    The purpose of this study was to evaluate the radiologic findings of lumbosacral transitional vertebrae (LSTV), as seen on plain radiographs and MRI, and to compare the incidence of combined diseases between unilateral and bilateral groups. We retrospectively evaluated the plain radiographs and MR images of 63 patients with LSTV, classifying its type according to Castellvi's criteria, and evaluated disc herniations, facet joint osteoarthritic change, scoliosis, and spondylolisthesis. We then compared the incidence of each combined diseases between unilateral and bilateral groups, and as a control group, 63 patients without LSTV were also evaluated. Forty of 63 cases of LSTV (63.5%) were bilateral, and 23 (36.5%) unilateral. According to Castellvi's criteria, the incidence of type I was 41.3% (unilateral 7 cases, bilateral 19), type III 30.2% (unilateral 8 cases, bilateral 11), type II 23.8% (unilateral 8 cases, bilateral 7), and type IV 4.8% (unilateral 0 cases, bilateral 3). With combined diseases, the incidence of disc herniation was 66.7% (unilateral 15 cases, bilateral 27), moderate to severe facet joint osteoarthritic change 28.6% (unilateral 11 cases, bilateral 7), scoliosis 27.0% (unilateral 9 cases, bilateral 8), and spondylolisthesis 9.5% (unilateral 2 cases, bilateral 4). The incidence of facet joint osteoarthritic change was significantly higher in the unilateral group (47.8%) than in the bilateral group (17.5%) (p =3D0.02), and scoliosis occurred at a higher rate in the unilateral group (39.1%) than in the bilateral group (20.0%) (p=3D0.18). There was, however, no significant difference in the incidence of disc herniation and spondylolisthesis between the two groups (unilateral group: 65.2% and 8.7%; bilateral group: 67.5% and 10.0%, respectively). With LSTV, the incidence of facet joint osteoarthritic change was significantly higher in the unilateral group than in the bilateral group, and scoliosis also showed a higher rate of occurrence in

  18. Safety aspects and rational use of a naproxen + esomeprazole combination in the treatment of rheumatoid disease

    Directory of Open Access Journals (Sweden)

    David N Roberts


    Full Text Available David N Roberts1, Philip B Miner21Department of Internal Medicine, Digestive Diseases Section, University of Oklahoma, 2Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, USAAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are widely prescribed for reduction of pain and inflammation, particularly in the setting of rheumatologic disorders. While effective, they are associated with risks, including nephrotoxicity, gastrointestinal inflammation, peptic ulcer disease, and worsened cardiovascular outcomes. After development of cyclo-oxygenase 2 inhibitors to minimize gastrointestinal complications, early use revealed increased cardiovascular event rate risk, and retrospective analysis of traditional NSAIDs revealed similar concerns, with the exception of naproxen. PN400 is a fixed-dose combination formulation designed to provide sequential delivery of a nonenteric-coated, immediate-release esomeprazole 20 mg mantle followed by an enteric-coated naproxen 500 mg core. This review summarizes the pharmacokinetics, benefits, safety, and tolerability of PN400. Phase I trials demonstrated pharmacokinetics consistent with its formulation, and at different esomeprazole combination doses, PN400 containing esomeprazole 20 mg was the lowest dose that still resulted in substantial sustained increases of gastric pH > 4. In two Phase III trials (Study 301 and Study 302, PN400 resulted in a significant reduction in gastric ulcers relative to enteric-coated naproxen (4.1% to 23.1% in Study 301, 7.1% to 24.3% in Study 302. Discontinuation due to NSAID-associated upper gastrointestinal adverse events or duodenal ulcers was significantly less in PN400 patients (3.2% to 12%, P < 0.001, in Study 301; 4.8% to 11.9%, P = 0.009, in Study 302. Two subjective patient indices were utilized to assess tolerability, ie, the Severity of Dyspepsia Assessment (SODA and Overall Treatment Evaluation of Dyspepsia (OTE-DP. Patients with PN400 had significantly

  19. Epstein–Barr Virus+ Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders

    Directory of Open Access Journals (Sweden)

    Thomas Magg


    Full Text Available Epstein–Barr virus positive (EBV+ smooth muscle tumors (SMTs constitute a very rare oncological entity. They usually develop in the context of secondary immunodeficiency caused by human immunodeficiency virus infection or immunosuppressive treatment after solid organ transplantation. However, in a small fraction of predominantly pediatric patients, EBV+ SMTs may occur in patients with primary immunodeficiency disorders (PIDs, such as GATA2 and CARMIL2 deficiency. In secondary immunodeficiencies and when the underlying condition can not be cured, the treatment of EBV+ SMTs is based on surgery in combination with antiretroviral and reduced or altered immunosuppressive pharmacotherapy, respectively. Importantly, without definitive reconstitution of cellular immunity, long-term survival is poor. This is particularly relevant for patients with EBV+ SMTs on the basis of PIDs. Recently, allogeneic hematopoietic stem cell transplantation resulted in cure of immunodeficiency and EBV+ SMTs in a GATA2-deficient patient. We propose that in the absence of secondary immunodeficiency disorders patients presenting with EBV+ SMTs should be thoroughly evaluated for PIDs. Allogeneic hematopoietic stem cell transplantation should be taken into consideration, ideally in the setting of a prospective clinical trial.

  20. Disease: H00088 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available V, Hovhannisyan H, Majzoub J, Miller DT. Genetic diagnosis of primary immune deficiencies. Immunol Allerg...ieties Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin

  1. Disease: H00094 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00094 Immunodeficiency associated with DNA repair defects, including the following six disea...D Recombinational DNA repair and human disease. Mutat Res 509:49-78 (2002) PMID:1...7162365 (gene) Kumar A, Teuber SS, Gershwin ME. Current perspectives on primary immunodeficiency diseases. C...trom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. Primary immunodeficiency diseases: an ...update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol 120:776-94 (2007) ...


    Directory of Open Access Journals (Sweden)

    E. A. Latysheva


    Full Text Available The problems of primary immunodeficiency in Russia and the ways of solving of them are discussed in the article. Primary immunodeficiency is a group of rare diseases, so awareness of this pathology in the medical community and among patients is very low. This leads to late diagnosis and inadequate treatment of patients with such conditions. The result of the late beginning of treatment is early development of disability, and the high mortality rate of patients, as well as the high costs of the treatment of complications of primary immunodeficiency and sick-leave certificates for the government. Today in time and adequate therapy allows patients not only to reach adulthood without signs of disability, and to lead an active way of life, but to have healthy children. Given the high cost of therapy in many countries, the issue of providing patients with life-saving drugs remains unresolved. The global practice is to involve social organizations and funds. One of the foundations supporting educational programs, development of laboratories and research in the field of primary immunodeficiency is the Foundation of the Jeffrey Modell. A network of centres for primary immunodeficiency supported by the Jeffrey Modell Foundation (JMF-centers has started its functioning over the territory of the Russian Federation since 2011 in order to improve diagnostics and treatment of patients with primary immunodeficiency. A brief description of activity of these centers is presented in the article.

  3. Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2

    DEFF Research Database (Denmark)

    Lindegaard Pedersen, Brian; Bækgaard, Niels; Quistorff, Bjørn


    BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests...... tested applying high resolution oxygraphy on isolated muscle fibers. RESULTS: The NIRS exercise tests showed evidence of mitochondrial dysfunction in the PAD+T2D group by a longer recovery of the deoxygenation resulting from exercise in spite of a higher exercise oxygenation level compared to the PAD...... were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function...


    Directory of Open Access Journals (Sweden)

    A.S. Ivanov


    Full Text Available Aim. To present rare clinical observation of successful surgical treatment of the patient with double-chamber right ventricle in combination with ventricular septal defect, subaortic fi brosis and muscular stenosis, insufficiency of the aortic valve and extrahepatic portal hypertension.Description. Patient F., 15 years old, was diagnosed with Congenital Heart Disease – double-chambered right ventricle, ventricular septal defect. Fibromuscular subaortic stenosis. Aortic valve insuffi ciency II. Circulatory failure II A., functional class III. Extrahepatic portal hypertension. Splenomegaly. Thrombocytopenia. The state after the imposition of splenorenal anastomosis in September 1998 and the imposition of mesocaval H-shaped anastomosis in 1998. Non-functioning anastomoses. Patient indicated for surgical correction of CHD, however, given the low level of platelets, expressed splenomegaly, leucopenia, the patient was referred for a preliminary treatment to Rogachev’s Pediatric Hematology, Oncology and Immunology Center. The treatment (stimulating thrombopoiesis using romiplostim gave no signifi cant effect. Platelet count reached 70–90 Å~ 109. Seeing of frequent bleeding from esophageal varices, the patient underwent varix sclerosis. At the time of hospitalization – no esophageal varices. The patient appealed to V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs where he was recommended for surgical treatment.Result. The patient performed surgery: radical correction of CHD: resection of the stenosis of the outfl ow tract of the right ventricle, subaortic stenosis resection, closure of ventricular septal defect, AV plasty under cardiopulmonary bypass. The early postoperative period was uneventful. Leukopenia was observed to 1,2 Å~ 109, thrombocytopenia 70–90 Å~ 109. Despite the low level of platelets bleeding in pre-and postoperative period was not registered. Antibiotic therapy with tienam. Good postoperative

  5. A combined disease management and process modeling approach for assessing and improving care processes: a fall management case-study

    NARCIS (Netherlands)

    Askari, Marjan; Westerhof, Richard; Eslami, Saied; Medlock, Stephanie; de Rooij, Sophia E.; Abu-Hanna, Ameen


    To propose a combined disease management and process modeling approach for evaluating and improving care processes, and demonstrate its usability and usefulness in a real-world fall management case study. We identified essential disease management related concepts and mapped them into explicit

  6. Effects of a fixed combination of perindopril and indapamide in patients with type 2 diabetes and chronic kidney disease

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Ninomiya, Toshiharu; Perkovic, Vlado; Woodward, Mark; Zoungas, Sophia; Cass, Alan; Cooper, Mark; Grobbee, Diederick E.; Mancia, Giuseppe; Mogensen, Carl Eric; Neal, Bruce; Chalmers, John


    Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril-indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to

  7. Patients’ Views on a Combined Action Observation and Motor Imagery Intervention for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Judith Bek


    Full Text Available Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson’s disease (PD, methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD.

  8. Patients' Views on a Combined Action Observation and Motor Imagery Intervention for Parkinson's Disease. (United States)

    Bek, Judith; Webb, Jordan; Gowen, Emma; Vogt, Stefan; Crawford, Trevor J; Sullivan, Matthew S; Poliakoff, Ellen


    Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson's disease (PD), methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD.

  9. Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents. (United States)

    Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M


    To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Statins and renin-angiotensin system inhibitor combination treatment to prevent cardiovascular disease. (United States)

    Lee, Hae-Young; Sakuma, Ichiro; Ihm, Sang-Hyun; Goh, Choong-Won; Koh, Kwang Kon


    Hypercholesterolemia and hypertension are common risk factors for cardiovascular disease (CVD). Updated guidelines emphasize target reductions of overall cardiovascular risks. Experimental studies have shown reciprocal relationships between insulin resistance (IR) and endothelial dysfunction. Hypercholesterolemia and hypertension have a synergistic deleterious effect on IR and endothelial dysfunction. Unregulated renin-angiotensin system (RAS) is important in the pathogenesis of atherosclerosis and hypertension. Various strategies with different classes of antihypertensive medications to reach target goals have failed to reduce residual CVD risk further. Of interest, treating moderate cholesterol elevations with low-dose statins in hypertensive patients reduced CVD risk by 35-40% further. Therefore, statins are important in reducing CVD risk. Unfortunately, statin therapy causes IR and increases the risk of type 2 diabetes mellitus. RAS inhibitors improve both endothelial dysfunction and IR. Further, cross-talk between hypercholesterolemia and RAS exists at multiple steps of IR and endothelial dysfunction. In this regard, combined therapy with statins and RAS inhibitors demonstrates additive/synergistic effects on endothelial dysfunction and IR in addition to lowering cholesterol levels and blood pressure when compared with either monotherapy in patients. This is mediated by both distinct and interrelated mechanisms. Therefore, combined therapy with statins and RAS inhibitors may be important in developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome, or obesity to prevent CVD.  

  11. Obstructive sleep apnea combined dyslipidemia render additive effect on increasing atherosclerotic cardiovascular diseases prevalence. (United States)

    Cao, Zhiyong; Zhang, Ping; He, Zhiqing; Yang, Jing; Liang, Chun; Ren, Yusheng; Wu, Zonggui


    Current study was designed to investigate the effects of obstructive sleep apnea (OSA) combined dyslipidemia on the prevalence of atherosclerotic cardiovascular diseases (ASCVD). This was a cross-sectional study and subjects with documented dyslipidemia and without previous diagnosis of OSA were enrolled. Polysomnography was applied to evaluate apnea-hypopnea index (AHI). Based on AHI value, subjects were classified into four groups: without OSA, mild, moderate and severe OSA groups. Clinical characteristics and laboratory examination data were recorded. Relationship between AHI event and lipid profiles was analyzed, and logistic regression analysis was used to evaluate the effects of OSA combined dyslipidemia on ASCVD prevalence. Totally 248 subjects with dyslipidemia were enrolled. Compared to the other 3 groups, subjects with severe OSA were older, male predominant and had higher smoking rate. In addition, subjects with severe OSA had higher body mass index, waist-hip ratio, blood pressure, and higher rates of overweight and obesity. Serum levels of fasting plasma glucose, glycated hemoglobin, LDL-C and CRP were all significantly higher. ASCVD prevalence was considerably higher in subjects with severe OSA. AHI event in the severe OSA group was up to 35.4 ± 5.1 events per hour which was significantly higher than the other groups (P dyslipidemia plus no-OSA group (reference group), OSA enhanced ASCVD risk in subjects with dyslipidemia, regardless of OSA severity. After extensively adjusted for confounding variables, the odds of dyslipidemia plus mild-OSA was reduced to insignificance. While the effects of moderate- and severe-OSA on promoting ASCVD risk in subjects with dyslipidemia remained significant, with severe-OSA most prominent (odds ratio: 1.52, 95% confidence interval: 1.13-2.02). OSA combined dyslipidemia conferred additive adverse effects on cardiovascular system, with severe-OSA most prominent.

  12. Combined exposure of carps (Cyprinus carpio L.) to cyanobacterial biomass and white spot disease. (United States)

    Palikova, Miroslava; Navratil, Stanislav; Papezikova, Ivana; Ambroz, Petr; Vesely, Tomas; Pokorova, Dagmar; Mares, Jan; Adamovsky, Ondrej; Navratil, Lukas; Kopp, Radovan


    Under environmental conditions, fish can be exposed to multiple stressors including natural toxins and infectious agents at the same time. This study brings new knowledge on the effects of controlled exposure to multiple stressors in fish. The aim of this study was to test the hypothesis that influence of cyanobacterial biomass and an infection agent represented by the white spot disease can combine to enhance the effects on fish. Common carps were divided into four groups, each with 40 specimens for 20 days: control group, cyanobacterial biomass exposed group, Ichthyophthirius multifiliis-infected fish (Ich) and cyanobacterial biomass-exposed fish + Ichthyophthirius multifiliis-infected fish. During the experiment we evaluated the clinical signs, mortality, selected haematological parameters, immune parameters and toxin accumulation. There was no mortality in control fish and cyanobacterial biomass-exposed fish. One specimen died in Ichthyophthirius multifiliis-infected fish and the combined exposure resulted in the death of 13 specimens. The whole leukocyte counts (WBC) of the control group did not show any significant differences. Cyanobacteria alone caused a significant increase of the WBC on day 13 (p≤0.05) and on day 20 (p≤0.01). Also, I. multifiliis caused a significant elevation of WBC (p≤0.01) on day 20. Co-exposition resulted in WBC increased on day 13 and decrease on day 20, but the changes were not significant. It is evident from the differential leukocyte counts that while the increase of WBC in the group exposed to cyanobacteria was caused by elevation of lymphocytes, the increase in the group infected by I. multifiliis was due to the increase of myeloid cells. It well corresponds with the integral of chemiluminescence in the group infected by I. multifiliis, which is significantly elevated on day 20 in comparison with all other groups. We can confirm additive action of different agents on the immune system of fish. While single agents seemed to


    Directory of Open Access Journals (Sweden)

    M. A. Popova


    Full Text Available The research objective is to determine the state of endothelium-dependent and endothelium-independent vasodilatation in patients with coronary heart disease (CHD associated with chronic obstructive pulmonary disease (COPD.Material and methods. In the cross-sectional study included 122 patients with CHD associated with COPD: 68 people of them are patients with stable angina without acute coronary events in history and 54 patients with acute ST segment elevation myocardial infarction (STEMI. Comparison group comprised 53 patients with stable angina and 51 patients after STEMI without concomitant COPD. Patients were included if they met the following inclusion criteria: male, age <60 years, verified forms of CHD (stable angina, STEMI, documented with COPD without exacerbation and forced expiratory volume in 1 second > 30% in the groups with CHD and COPD. Arterial endothelial function was tested with high-resolution ultrasonography: brachial artery diameter was measured at rest, after flow increase (which causes endothelium-dependent dilatation, and after administration of sublingual nitroglycerin (an endothelium-independent dilator.Results. We found that endothelial dysfunction in patients with acute and chronic forms of CHD in combination with COPD are more pronounced than in isolated CHD.Conclusion. Expressed depression functional vascular reserve in patients with CHD associated with COPD, should be taken into account when conducting individualized therapy of these patients.

  14. Malnutrition risk questionnaire combined with body composition measurement in malnutrition screening in inflammatory bowel disease. (United States)

    Csontos, Ágnes Anna; Molnár, Andrea; Piri, Zsolt; Pálfi, Erzsébet; Miheller, Pál


    The purpose of malnutrition screening is to predict the probability of a worse outcome due to nutritional factors. The Malnutrition Universal Screening Tool (MUST) can be used for screening in inflammatory bowel disease (IBD); however, it does not provide details about body composition. Our aim was to assess the body composition and combine this with the MUST method to screen risk of malnutrition and sarcopenia. A total of 173 IBD outpatients were enrolled in this cross-sectional study. The MUST scale indicated 21.4% of IBD patients to be at risk of malnutrition. A risk of sarcopenia was detected in 27.7%. However, one third of these patients were not considered to be at risk by their MUST score. Furthermore, Crohn's disease (CD) patients had a strongly unfavorable fat-free mass index (FFMI) value compared to ulcerative colitis (UC) patients, and these differences were significant among men (FFMI: 18.62 ± 2.16 vs 19.85 ± 2.22, p = 0.02, in CD and UC males, respectively). As sarcopenia is a relevant prognostic factor, the MUST method should be expanded to include body composition analysis to detect more IBD patients at risk of malnutrition and sarcopenia in order to start their nutritional therapy immediately.

  15. Critical Care Medicine and Infectious Diseases: An Emerging Combined Subspecialty in the United States. (United States)

    Kadri, Sameer S; Rhee, Chanu; Fortna, Gregory S; O'Grady, Naomi P


    The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Postnatal transmission of human immunodeficiency virus type 1: the breast-feeding dilemma. (United States)

    Van de Perre, P


    Human milk has been considered only recently as a source of transmission for the human immunodeficiency virus. The estimated postnatal transmission rate from mothers who acquired human immunodeficiency virus infection while lactating is 26% (95% confidence interval 13% to 39%) and may be in the range of 8% to 18% from mothers who were infected before becoming pregnant. Risk factors for postnatal transmission include maternal immune deficiency and the presence of human immunodeficiency virus-infected cells in milk. Some milk factors may be protective against postnatal transmission such as specific immunoglobulin A and immunoglobulin M and a molecule able to inhibit the binding of human immunodeficiency virus to CD4. In addition to its safety and its birth-spacing properties, breast-feeding provides immunologic protection and an ideal nutritional content to the infant. In a poor hygienic environment artificial feeding dramatically increases morbidity and mortality from diarrheal diseases and respiratory infections. Consequently, according to our current knowledge the World Health Organization and the United Nations Children's Fund reasonably recommend continuing breast-feeding promotion in women living in settings where infectious diseases and malnutrition are the primary causes of infant deaths such as in many developing countries. In settings where infectious diseases and malnutrition are not the primary causes of infant deaths, such as in most of the settings in the developed world, the advisory group recommends against breast-feeding for mothers with proved human immunodeficiency virus-1 infection.

  17. Early outcomes of one-stage combined osteotomy in Legg-Calve´-Perthes disease. (United States)

    Bhuyan, Basant Kumar


    Legg-Calve´-Perthes disease (LCPD) is an idiopathic avascular necrosis of the femoral head. There are multiple approaches to the treatment of LCPD ranging from conservative management to a wide variety of surgical methods. Conservative management necessitates extreme degrees of abduction in an orthosis for a longer period of time which further jeopardize capital femoral head vascularity. Surgical containment methods are used in cases where it is desirable. Initial surgical containment methods are varus or varus-derotational osteotomy of the proximal femur or an innominate osteotomy as described by Salter and other pelvic osteotomies. The purpose of this study was to describe the early results of containment methods by one-stage combined osteotomy (femoral varus osteotomy and Salter innominate osteotomy) in patients with severe LCPD. 23 children were operated in the age group of 4-9 years for LCPD by one-stage combined osteotomy procedure between January 2005 and June 2012. There were 19 boys and 4 girls, left hip involved in 10 cases and right in 13 cases. Preoperatively, they were classified according to Catterall, Joseph's stage and lateral pillar (LP) classification. Postoperatively, clinical results were evaluated in accordance with Ratliff classification and radiological assessment was made by Mose's index, modified Stulberg classification and Epiphyseal extrusion index. Seventeen hips were Catterall group III, 6 in group IV and all had two or more "head-at-risk" signs. There were 2 patients with stage IIA, 15 were in stage IIB and 6 were in stage IIIA as classified by Joseph's stage of disease. According to LP classification, 11 patients were group B, 3 were group B/C and 9 were in group C. At an average followup of 5.4 years (range 2-9.5 years), the clinical results were good in 12, fair in 9 and poor in 2. According to Mose scale, 8 patients had good results, 13 fair results and 2 had poor results. Based on modified Stulberg classification, there were 10

  18. Visceral Leishmaniasis Treated with Antimonials/Paromomycin followed by Itraconazole/Miltefosine after Standard Therapy Failures in a Human Immunodeficiency Virus–Infected Patient


    Barragán, Patricia; López-Velez, Rogelio; Olmo, Montserrat; Podzamczer, Daniel


    Visceral leishmaniasis is an opportunistic infection that affects human immunodeficiency virus–infected persons in leishmaniasis-endemic areas. The standard treatment may not be effective and relapses are common. We report the case of a human immunodeficiency virus-1–infected patient who had several relapses of visceral leishmaniasis after treatment with standard therapies and responded to a combined therapy.

  19. Acquired immunodeficiency syndrome and its ocular complications

    Directory of Open Access Journals (Sweden)

    Rao Narsing


    Full Text Available Human immunodeficiency virus infection is the first major pandemic of the 20th century. At present, almost 10 million people are known to be infected with this virus, and it is estimated that by the year 2000, approximately 40 million people will be infected. Transmission of this deadly infection is predominantly by sexual contact. Individuals infected with this virus pass through several predictable stages with progressive decrease in circulating CD4+ T cells. During the advanced stage, these patients develop various opportunistic infections or malignancies, or both. It is this advanced stage that was first recognized as AIDS, which has a 100% mortality rate. The opportunistic organisms that can involve the eye in patients with AIDS include cytomegalovirus, herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, Candida, and others. Intraocular lesions from these agents often represent disseminated infections. Visual morbidity occurs secondary to retinitis due to cytomegalovirus, herpes zoster, or Toxoplasma gondii. Anti-viral agents such as ganciclovir or foscarnet are effective against cytomegalovirus infection. The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important. Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations. In the AIDS patient, the ophthalmologist thus has an opportunity to make not only a slight-saving, but also life-saving diagnosis of disseminated opportunistic infections.

  20. Disease: H00104 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00104 Alternative complement pathway component defects, including the following four diseases...primary immunodeficiency diseases. Clin Dev Immunol 13:223-59 (2006) PMID:17952897 (gene) Geha RS, Notarange...hs HD, Puck JM, Roifman C, Seger R, Wedgwood J. Primary immunodeficiency diseases: an update from the Intern

  1. Epidemiological Patterns of Human Immunodeficiency Virus and ...

    African Journals Online (AJOL)

    Olaleye Received: July 2007. Accepted (Revised):. October 2007. Published. January 2008. Full Length Research Article. Epidemiological Patterns of Human. Immunodeficiency Virus and Herpes Simplex. Virus Co-Infection in Ibadan, Nigeria.

  2. Perceptions and knowledge about the acquired immunodeficiency ...

    African Journals Online (AJOL)

    Perceptions and knowledge about the acquired immunodeficiency syndrome among students in university residences. R.H. Friedland, S.K. Jankelowitz, M de Beer, C De Klerk, V. Khoury, T. Csizmadia, G.N. Padayachee, S. Levy ...

  3. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases. (United States)

    Bahiru, Ehete; de Cates, Angharad N; Farr, Matthew Rb; Jarvis, Morag C; Palla, Mohan; Rees, Karen; Ebrahim, Shah; Huffman, Mark D


    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this

  4. Psychosocial issues in pediatric human immunodeficiency virus. (United States)

    Adler, R K


    This article discusses the psychosocial issues associated with pediatric human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). Using a psychosocial model instead of the usual medical or rehabilitation model will challenge speech-language pathologists to incorporate an understanding of the psychosocial stresses that affect a child's progression through HIV/AIDS and ensure that they receive adequate consideration in a total treatment model. A case study illustrates the relationship between communication disorders and HIV/AIDS.

  5. TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic?

    Directory of Open Access Journals (Sweden)

    Ashish eMarwaha


    Full Text Available In 2005 a newly discovered T helper cell subset that secreted interleukin (IL-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction caused in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn’s disease in the clinical trials of a Secukiumab (AIN457, a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cell can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory disease that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases.

  6. Multimorbidity as specific disease combinations, an important predictor factor for mortality in octogenarians: the Octabaix study

    Directory of Open Access Journals (Sweden)

    Ferrer A


    Full Text Available Assumpta Ferrer,1 Francesc Formiga,2,3 Héctor Sanz,4 Jesús Almeda,5,6 Glòria Padrós7 On behalf of the Octabaix Study Group 1Primary Healthcare Department, Centre ‘El Plà’, DAP Metropolitana Sud ICS, 2Geriatric Unit, Internal Medicine Service, Hospital Universitari de Bellvitge, L´Hospitalet de Llobregat, Barcelona, 3Bellvitge Biomedical Research Department Institute, IDIBELL, L’Hospitalet de Llobregat, 4ISGlobal, Barcelona Ctr Int Health Res (CRESIB, Hospital Clínic – Barcelona University, 5Support Unit Research for Primary Care, Primary Health Care Department of Costa Ponent, IDIAP, ICS, 6CIBER Department of Epidemiology Service (CIBERESP, 7Clinical Laboratory Department, L´Hospitalet de Llobregat, Barcelona, Spain Background: The population is aging and multimorbidity is becoming a common problem in the elderly.Objective: To explore the effect of multimorbidity patterns on mortality for all causes at 3- and 5-year follow-up periods.Materials and methods: A prospective community-based cohort (2009–2014 embedded within a randomized clinical trial was conducted in seven primary health care centers, including 328 subjects aged 85 years at baseline. Sociodemographic variables, sensory status, cardiovascular risk factors, comorbidity, and geriatric tests were analyzed. Multimorbidity patterns were defined as combinations of two or three of 16 specific chronic conditions in the same individual.Results: Of the total sample, the median and interquartile range value of conditions was 4 (3–5. The individual morbidities significantly associated with death were chronic obstructive pulmonary disease (COPD; hazard ratio [HR]: 2.47; 95% confidence interval [CI]: 1.3; 4.7, atrial fibrillation (AF; HR: 2.41; 95% CI: 1.3; 4.3, and malignancy (HR: 1.9; 95% CI: 1.0; 3.6 at 3-year follow-up; whereas dementia (HR: 2.04; 95% CI: 1.3; 3.2, malignancy (HR: 1.84; 95% CI: 1.2; 2.8, and COPD (HR: 1.77; 95% CI: 1.1; 2.8 were the most associated with

  7. Recent advances in treatment of severe primary immunodeficiencies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Andrew Gennery


    Full Text Available Primary immunodeficiencies are rare, inborn errors that result in impaired, disordered or uncontrolled immune responses. Whilst symptomatic and prophylactic treatment is available, hematopoietic stem cell transplantation is an option for many diseases, leading to cure of the immunodeficiency and establishing normal physical and psychological health. Newborn screening for some diseases, whilst improving outcomes, is focusing research on safer and less toxic treatment strategies, which result in durable and sustainable immune function without adverse effects. New conditioning regimens have reduced the risk of hematopoietic stem cell transplantation, and new methods of manipulating stem cell sources should guarantee a donor for almost all patients. Whilst incremental enhancements in transplantation technique have gradually improved survival outcomes over time, some of these new applications are likely to radically alter our approach to treating primary immunodeficiencies.

  8. Immunodeficiency in a Child with Rapadilino Syndrome: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    M. M. G. Vollebregt


    Full Text Available Rapadilino syndrome is a genetic disease characterized by a characteristic clinical tableau. It is caused by mutations in RECQL4 gene. Immunodeficiency is not described as a classical feature of the disease. We present a 2-year-old girl with Rapadilino syndrome with important lymphadenopathies and pneumonia due to disseminated Mycobacterium lentiflavum infection. An immunological work-up showed several unexpected abnormalities. Repeated blood samples showed severe lymphopenia. Immunophenotyping showed low T, B, and NK cells. No Treg cells were seen. T cell responses to stimulations were insufficient. The IL12/IL23 interferon gamma pathway was normal. Gamma globulin levels and vaccination responses were low. With this report, we aim to stress the importance of screening immunodeficiency in patients with RECQL4 mutations for immunodeficiency and the need to further research into its physiopathology.

  9. Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

    Directory of Open Access Journals (Sweden)

    Asghar Aghamohammadi


    Full Text Available Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs have been isolated from primary immunodeficiency (PID patients exposed to oral poliovirus vaccine (OPV. Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2% excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8% were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2. Non-polio enteroviruses were detected in 30 patients (4.7%. Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

  10. Combining machine learning, crowdsourcing and expert knowledge to detect chemical-induced diseases in text. (United States)

    Bravo, Àlex; Li, Tong Shu; Su, Andrew I; Good, Benjamin M; Furlong, Laura I


    Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects.Database URL:¼en#.VsL3yDLWR_V. © The Author(s) 2016. Published by Oxford University Press.

  11. The Unique and Combined Effects of Apathy and Depression on Cognition in Parkinson's Disease. (United States)

    Cohen, Matthew L; Aita, Stephen; Mari, Zoltan; Brandt, Jason


    Apathy and depression are associated with poor cognition in patients with Parkinson's disease (PD). However, the cognitive signature of each syndrome is not well understood. The cognitive consequences of having apathy or depression, versus apathy and depression, are also unclear. This study investigated the unique and combined effects of apathy and depression on cognition in PD patients. PD patients were identified from a clinical research database as having self-reported apathy (n = 21), depression (n = 11), or both (n = 43). PD patients without apathy or depression served as the Control group (n = 49). The groups were of similar age, education, disease severity, age of symptom onset, and medication status. A multivariate analysis of variance (MANOVA) compared the groups on 17 neuropsychological test scores in the domains of attention, motor and psychomotor speed, construction, language, episodic memory, and executive functioning. There was a significant overall effect of group: F(18,276) = 2.12, p = 0.006, ηp2=0.12. Univariate analyses and planned contrasts revealed medium-sized effects distinguishing only the control group and the group with both apathy and depression (ηp2=0.06-0.12) on measures of verbal fluency and manual, processing, and psychomotor speed. PD patients with apathy alone or depression alone did not perform worse than PD controls on neuropsychological tests. Patients with apathy and depression performed worse than controls, but only on speed-based measures. This suggests that apathy and depression are associated with the same or similar circuits as those of cognitive and motor speed.

  12. Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease. (United States)

    Hoshino, Taro; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Mori, Honami; Yoshida, Izumi; Tabei, Kaoru


    Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

  13. Combining insulins with oral antidiabetic agents: effect on hyperglycemic control, markers of cardiovascular risk and disease

    Directory of Open Access Journals (Sweden)

    Kjeld Hermansen


    Full Text Available Kjeld Hermansen, Lene Sundahl Mortensen, Marie-Louise HermansenDepartment of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus, DenmarkAbstract: Patients with type 2 diabetes mellitus (T2DM have an increased risk of cardiovascular disease (CVD. Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and – with some analogs – limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.Keywords: diabetes mellitus, type 2 diabetes, cardiovascular disease, hyperglycemia, insulin, oral antidiabetic drugs

  14. Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. (United States)

    Singhi, Aatur D; Goyal, Alka; Davison, Jon M; Regueiro, Miguel D; Roche, Robyn L; Ranganathan, Sarangarajan


    The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings

  15. Biventricular thrombi in dilated cardiomyopathy in a patient with human immunodeficiency virus infection: a case report. (United States)

    Nkoke, Clovis; Kuate, Liliane Mfeukeu; Luchuo, Engelbert Bain; Edie, Sandrine Dikosso; Boombhi, Jerome; Menanga, Alain


    Sub-Saharan Africa is undergoing epidemiological transition with an increase in the prevalence of cardiovascular diseases that will add to the already devastating burden of infectious diseases such as human immunodeficiency virus infection. Human immunodeficiency virus infection is increasingly being recognized as an important etiological factor for dilated cardiomyopathy with the potential complication of intraventricular thrombus. However, biventricular thrombi are extremely rare. We report on a rare finding of biventricular thrombi in dilated cardiomyopathy in a patient with human immunodeficiency virus infection in Cameroon. A 52-year old Cameroonian male patient with human immunodeficiency virus infection since 4 years, longstanding heavy alcohol consumption and cigarette smoking presented with gradually worsening shortness of breath, fatigue, persistent dry cough and lower extremity swelling of about two weeks duration. Congestive heart failure was diagnosed. Echocardiography showed left ventricular chamber enlargement with severe left ventricular systolic dysfunction and biventricular thrombi. The thrombi were immobile and regular in configuration, suggesting they were old. He was treated with a conventional heart failure treatment including loop diuretics and angiotensin converting enzyme inhibitors and anticoagulants for the biventricular thrombi. Six months later, a control echocardiography showed a significant decrease in the size of the thrombi. There was no evidence of systemic or pulmonary embolization during follow up. Dilated cardiomyopathy may be seen in patients with human immunodeficiency virus infection, although other mechanisms needs to be assessed, but the occurrence of biventricular thrombi is rare.

  16. Human Immunodeficiency Virus Infection And Hypertension. Is There A Connection? (United States)

    Sanidas, Elias; Papadopoulos, Dimitris P; Velliou, Maria; Tsioufis, Kostas; Barbetseas, John; Papademetriou, Vasilios


    Data support that hypertension is prevalent among HIV patients contributing to increased risk of cardiovascular disease. Immunodeficiency and prolonged antiretroviral treatment along with common risk factors including older age, male gender and high body mass index might conduce to greater incidence of hypertension. The purpose of this review was to summarize recent evidence of the increased cardiovascular risk in these patents linking HIV infection to hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email:

  17. Combining Transcranial Magnetic Stimulation and Electroencephalography May Contribute to Assess the Severity of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Petro Julkunen


    Full Text Available Alzheimer's disease (AD is the most common form of old age dementia, and mild cognitive impairment (MCI often precedes AD. In our previous study (Julkunen et al. 2008, we found that the combination of transcranial magnetic stimulation (TMS and electroencephalography (EEG was able to find distinct differences in AD and MCI patients as compared to controls. Here, we reanalyzed the small sample data from our previous study with the aim to test the sensitivity of the TMS-EEG characteristics to discriminate control subjects (n=4 from MCI (n=5 and AD (n=5 subjects. Furthermore, we investigated how the TMS-EEG response characteristics related to the scores of the dementia rating scales used to evaluate the severity of cognitive decline in these subjects. We found that the TMS-EEG response P30 amplitude correlated with cognitive decline and showed good specificity and sensitivity in identifying healthy subjects from those with MCI or AD. Given the small sample size, further studies may be needed to confirm the results.

  18. Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD). (United States)

    Giordano, Marcello; Dominguez, Ligia J; Vitrano, Teresa; Curatolo, Massimiliano; Ferlisi, Anna; Di Prima, Anna; Belvedere, Mario; Barbagallo, Mario


    Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimer's disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n=100, mean age 78.4±4.3 years) initiated treatment with donepezil, 5mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the training program, and after 2 months of follow-up. There was a significant improvement in mini-mental state examination (MMSE) score (pintensive ROT training in Group A. MMSE was maintained after 2 months in-home ROT continuation. There were no significant changes in MMSE in drug-only treated patients (Group B) after 3 weeks, with a non-significant tendency to improvement in ADAS-Cog. Our results suggest benefit of an intensive ROT program in dementia patients receiving donepezil that seems to be maintained as far as ROT is continued by the caregiver. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  19. [A combined preparation stalevo in Parkinson's disease: a 5-year experience of continuous dopaminergic stimulation]. (United States)

    Fedotova, E Iu; Karabanov, A V; Poleshchuk, V V; Polevaia, E V; Mirkasimov, A F; Zagorovskaia, T B; Ivanova-Smolenskaia, I A; Illarioshkin, S N


    Levodopa remains a 'gold standard' for the treatment of patients with Parkinson's disease (PD), but its chronic use is accompanied by fluctuations of symptoms and dyskinesias related to unfavorable pharmacokinetics of levodopa and progressing loss of the nigrostriatal neurons. Prescribing inhibitors of catechol-O-methyl-transferase (enzyme of dopamine metabolism), entacapone or tolcapone, is a perspective approach to the correction of the above-mentioned complications. We followed up 402 patients with PD who received long-term therapy with a combined preparation Stalevo (levodopa/carbidopa/entacapone) for 2-5 years (2.9 ± 0.9 years). The high (92.8%) compliancy and good tolerance of the drug in patients with PD was shown. Stalevo leads to the stabilization of the response to levodopa, improvement of patients' functional capacities, increase in their everyday activity, and improvement of quality of life. Stalevo may be regarded as a preparation of choice in the treatment of motor complications in elderly patients, correction of night symptoms of PD and in a number of other clinical situations arising in hospital and outpatient practice.


    Directory of Open Access Journals (Sweden)

    G. V. Aniskevich


    Full Text Available The analysis of results of hybrid treatment of complex combined coronary and valve disease at patients with high level of operational risk between January 2005 and December 2010. The hybrid treatment of complex combined coronary and valve disease, provides performance of percutaneous coronary interventions (PCI in a combinati- on valve surgery. 118 patients, with a median age 64.4 ± 8.9 years, are included in research. 2 approaches of a hy- brid method of treatment – 2-Staged (n = 86 and a method «1-stop» (n = 32 are applied. The оperative mortality has made 4.2%. On the basis of the received results were the conclusion is drawn that at high-risk patients with complex combined coronary and valve disease the hybrid method of treatment allows to lower risk of operation. 

  1. [Promoting development of new traditional Chinese medicine by combination disease-syndrome and multi-objective optimization research in prevention and treatment of cardiovascular disease]. (United States)

    Wang, Jie; Guo, Li-li


    Differences in theories, application forms and evaluation standards about curative effect between traditional Chinese medicine and modern medicine lead to not only question safty and effectiveness but also hinder development and internationalization of traditional Chinese medicine. Combination of common problems in traditional Chinese new drug registration with experiences in research on traditional Chinese new drugs of prevention and treatment of coronary heart disease elucidate application value about theory of disease-syndrome combination and multi-objective optimization in several ways such as the indications positioning, preparation process optimization, preclinical efficacy evaluating and clinical assessmenting of efficacy and analysis development prospect.

  2. Clinical aspects of feline immunodeficiency and feline leukemia virus infection. (United States)

    Hartmann, Katrin


    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Management of Diabetes Mellitus in Patients with Acquired Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Miulescu Rucsandra Dănciulescu


    Full Text Available Acquired immunodeficiency syndrome (AIDS is a human immune system disease characterized by increased susceptibility to opportunistic infections, certain cancers and neurological disorders. The syndrome is caused by the human immunodeficiency virus (HIV that is transmitted through blood or blood products, sexual contact or contaminated hypodermic needles. Antiretroviral treatment reduces the mortality and the morbidity of HIV infection but is increasingly reported to be associated with increasing reports of metabolic abnormalities. The prevalence and incidence of diabetes mellitus in patients on antiretroviral therapy is high. Recently, a joint panel of American Diabetes Association (ADA and European Association for the Study of Diabetes (EASD experts updated the treatment recommendations for type 2 diabetes (T2DM in a consensus statement which provides guidance to health care providers. The ADA and EASD consensus statement concur that intervention in T2DM should be early, intensive, and uncompromisingly focused on maintaining glycemic levels as close as possible to the nondiabetic range. Intensive glucose management has been shown to reduce microvascular complications of diabetes but no significant benefits on cardiovascular diseases. Patients with diabetes have a high risk for cardiovascular disease and the treatment of diabetes should emphasize reduction of the cardiovascular factors risk. The treatment of diabetes mellitus in AIDS patients often involves polypharmacy, which increases the risk of suboptimal adherence

  4. Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete


    BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine...... if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease. METHODS: Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective...... cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. RESULTS: ECG changes were present in 907...

  5. Birth weight, childhood body mass index and risk of coronary heart disease in adults: combined historical cohort studies

    DEFF Research Database (Denmark)

    Andersen, Lise Geisler; Ängquist, Lars Henrik; Eriksson, Johan G


    Low birth weight and high childhood body mass index (BMI) is each associated with an increased risk of coronary heart disease (CHD) in adult life. We studied individual and combined associations of birth weight and childhood BMI with the risk of CHD in adulthood.......Low birth weight and high childhood body mass index (BMI) is each associated with an increased risk of coronary heart disease (CHD) in adult life. We studied individual and combined associations of birth weight and childhood BMI with the risk of CHD in adulthood....

  6. The human immunodeficiency virus preventive vaccine research at the French National Agency for acquired immunodeficiency syndrome research

    Directory of Open Access Journals (Sweden)

    Elizabeth Fischer


    Full Text Available The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS epidemic is of unprecedented gravity and is spreading rapidly, notably in the most disadvantaged regions of the world. The search for a preventive vaccine is thus an absolute priority. For over 10 years the French National Agency for AIDS research (ANRS has been committed to an original program combining basic science and clinical research. The HIV preventive vaccine research program run by the ANRS covers upstream research for the definition of immunogens, animal models, and clinical research to evaluate candidate vaccines. Most researchers in 2004 believe that it should be possible to obtain partial vaccine protection through the induction of a strong and multiepitopic cellular response. Since 1992, the ANRS has set up 15 phases I and II clinical trials in order to evaluate the safety and the capacity of the candidate vaccines for inducing cellular immune responses. The tested candidate vaccines were increasingly complex recombinant canarypox viruses (Alvac containing sequences coding for certain viral proteins, utilized alone or combined with other immunogens (whole or truncated envelope proteins. ANRS has also been developing an original strategy based on the utilization of lipopeptides. These comprise synthetic fragments of viral proteins associated with lipids that facilitate the induction of a cellular immune response. These approaches promptly allowed the assessment of a prime-boost strategy combining a viral vector and lipopeptides.

  7. Combined pathology of bone tissue: osteoporosis and osteomalacia in patient with Parkinson’s disease (Clinical case report

    Directory of Open Access Journals (Sweden)

    V.V. Povoroznyuk


    Full Text Available The article describes a case of combined osteoporosis and osteomalacia in a patient with Parkinson’s disease and vertebral pain syndrome. Osteomalacia caused by deficiency and metabolic disorders of vitamin D leads to osteoid mineralization impairment that greatly limits the possibilities of osteoporosis treatment. The treatment of Parkinson’s disease and osteotropic drugs contributed to decreasing intensity of the pain syndrome.

  8. Combined mucoactive therapy of diseases of the respiratory system associated with formation of a viscous secretion in children

    Directory of Open Access Journals (Sweden)

    S.P. Kryvopustov


    Full Text Available The article considers in detail the mechanisms of therapeutic action of various mucoactive agents. Modern approaches to mucoactive therapy of respiratory diseases in children are presented, they are accompanied by the formation of a viscous secretion. At the same time, the expediency of combined use of drugs having different mechanism of mucoactive action — ambroxol and carbocysteine is justified. In addition, it helps to increase the effectiveness of antibiotic therapy for respiratory diseases.

  9. Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Wang J


    Full Text Available Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1 1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China *These authors contributed equally to this work Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD in hypertensive adults. Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1 rapid decline in renal function and 2 annual rate of eGFR decline. Results: The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57. However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95 was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL levels. More importantly, there was an interaction

  10. Disease: H00091 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00091 T-B+Severe combined immunodeficiencies (SCIDs), including the following eight disea...a S, Andre-Schmutz I, Basile Gde S, de Villartay JP, Cavazzana-Calvo M. ... TITLE ... Severe combined immunodeficiency. A model disea

  11. Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction

    NARCIS (Netherlands)

    Sabin, C. A.; d'Arminio Monforte, A.; Friis-Moller, N.; Weber, R.; El-Sadr, W. M.; Reiss, P.; Kirk, O.; Mercie, P.; Law, M. G.; de Wit, S.; Pradier, C.; Phillips, A. N.; Lundgren, J. D.; Collins, S.; Loeliger, E.; Tressler, R.; Weller, I.; Friis-Møller, N.; Worm, S. W.; Sjøl, A.; Sawitz, A.; Rickenbach, M.; Pezzotti, P.; Krum, E.; Gras, L.; Balestre, E.; Sundström, A.; Poll, B.; Fontas, E.; Torres, F.; Petoumenos, K.; Kjaer, J.; de Wolf, F.; Zaheri, S.; Bronsveld, W.; Hillebrand-Haverkort, M. E.; Prins, J. M.; Bos, J. C.; Eeftinck Schattenkerk, J. K. M.; Geerlings, S. E.; Godfried, M. H.; Lange, J. M. A.; van Leth, F. C.; Lowe, S. H.; van der Meer, J. T. M.; Nellen, F. J. B.; Pogány, K.; van der Poll, T.; Ruys, Th A.; Sankatsing, S.; Steingrover, R.; van Twillert, G.; van der Valk, M.; van Vonderen, M. G. A.; Vrouenraets, S. M. E.; van Vugt, M.; Wit, F. W. M. N.; van Eeden, A.; ten Veen, J. H.; van Dam, P. S.; Roos, J. C.; Brinkman, K.; Frissen, P. H. J.; Weigel, H. M.; Mulder, J. W.; van Gorp, E. C. M.; Meenhorst, P. L.; Mairuhu, A. T. A.; Veenstra, J.; Danner, S. A.; van Agtmael, M. A.; Claessen, F. A. P.; Perenboom, R. M.; Rijkeboer, A.; van Vonderen, M.; Richter, C.; van der Berg, J.; van Leusen, R.; Vriesendorp, R.; Jeurissen, F. J. F.; Kauffmann, R. H.; Koger, E. L. W.; Bravenboer, B.; ten Napel, C. H. H.; Kootstra, G. J.; Sprenger, H. G.; Miesen, W. M. A. J.; Doedens, R.; Scholvinck, E. H.; ten Kate, R. W.; van Houte, D. P. F.; Polee, M.; Kroon, F. P.; van den Broek, P. J.; van Dissel, J. T.; Schippers, E. J.; Schreij, G.; van de Geest, P. J.; Verbon, A.; Koopmans, P. P.; Keuter, M.; Post, F.; van der Ven, A. J. A. M.; van der Ende, M. E.; Gyssens, I. C.; van der Feltz, M.; den Hollander, J. G.; de Marie, S.; Nouwen, J. L.; Rijnders, B. J. A.; de Vries, T. E. M. S.; Juttmann, J. R.; van de Heul, C.; van Kasteren, M. E. E.; Elisabeth, St; Schneider, M. M. E.; Bonten, M. J. M.; Borleffs, J. C. C.; Ellerbroek, P. M.; Hoepelman, I. M.; Jaspers, C. A. J. J.; Schouten, I.; Schurink, C. A. M.; Blok, W. L.; Tanis, A. A.; Groeneveld, P. H. P.; Salamon, R.; Beylot, J.; Dupon, M.; Le Bras, M.; Pellegrin, J. L.; Ragnaud, J. M.; Dabis, F.; Chêne, G.; Jacqmin-Gadda, H.; Thiébaut, R.; Lawson-Ayayi, S.; Lavignolle, V.; Blaizeau, M. J.; Decoin, M.; Formaggio, A. M.; Delveaux, S.; Labarerre, S.; Uwamaliya, B.; Vimard, E.; Merchadou, L.; Palmer, G.; Touchard, D.; Dutoit, D.; Pereira, F.; Boulant, B.; Morlat, P.; Bernard, N.; Bonarek, M.; Bonnet, F.; Coadou, B.; Gelie, P.; Jaubert, D.; Nouts, C.; Lacoste, D.; Dutronc, H.; Cipriano, G.; Lafarie, S.; Chossat, I.; Lacut, J. Y.; Leng, B.; Mercié, P.; Viallard, J. F.; Faure, I.; Rispal, P.; Cipriano, C.; Tchamgoué, S.; Djossou, F.; Malvy, D.; Pivetaud, J. P.; Chambon, D.; de La Taille, C.; Galperine, T.; Neau, D.; Ochoa, A.; Beylot, C.; Doutre, M. S.; Bezian, J. H.; Moreau, J. F.; Taupin, J. L.; Conri, C.; Constans, J.; Couzigou, P.; Castera, L.; Fleury, H.; Lafon, M. E.; Masquelier, B.; Pellegrin, I.; Trimoulet, P.; Moreau, F.; Mestre, C.; Series, C.; Taytard, A.; Law, M.; Anderson, J.; Lowe, K.; Mijch, A.; Watson, K.; Roth, N.; Wood, H.; Bloch, M.; Gowers, A.; Baker, D.; McFarlane, R.; Carr, A.; Cooper, D.; Chuah, J.; Fankhauser, W.; Mallal, S.; Skett, J.; Calvo, G.; Mateu, S.; Domingo, P.; Sambeat, M. A.; Gatell, J.; del Cacho, E.; Cadafalch, J.; Fuster, M.; Codina, C.; Sirera, G.; Vaqué, A.; Clumeck, N.; Gerard, M.; Kabeya, K.; Konopnicki, D.; Libois, A.; Payen, M. C.; van Laethem, Y.; Neaton, J.; Thompson, G.; Wentworth, D.; Luskin-Hawk, R.; Telzak, E.; Abrams, D. I.; Cohn, D.; Markowitz, M.; Crane, L. R.; Arduino, R.; Mushatt, D.; Friedland, G.; Perez, G.; Tedaldi, E.; Fisher, E.; Gordin, F.; Sampson, J.; Baxter, J.; Olsen, C. H.; Mocroft, A.; Vetter, N.; Karpov, I.; Vassilenko, A.; Colebunders, R.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Hansen, A. B. E.; Skinhøj, P.; Pedersen, C.; Zilmer, K.; Katlama, C.; Viard, J. P.; Girard, P. M.; Saint-Marc, T.; Vanhems, P.; Dabis, C.; Dietrich, M.; Manegold, C.; van Lunzen, J.; Stellbrink, H. J.; Staszewski, S.; Bieckel, M.; Goebel, F. D.; Fätkenheuer, G.; Rockstroh, J.; Schmidt, R. E.; Kosmidis, J.; Gargalianos, P.; Sambatakou, H.; Perdios, J.; Panos, G.; Filandras, A.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Burke, M.; Turner, D.; Pollack, S.; Hassoun, J.; Sthoeger, Z.; Maayan, S.; Vella, S.; Chiesi, A.; Arici, C.; Pristerá, R.; Mazzotta, F.; Gabbuti, A.; Esposito, R.; Bedini, A.; Chirianni, A.; Montesarchio, E.; Vullo, V.; Santopadre, P.; Narciso, P.; Antinori, A.; Franci, P.; Zaccarelli, M.; Lazzarin, A.; Castagna, A.; Viksna, L.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Bruun, J.; Maeland, A.; Ormaasen, V.; Knysz, B.; Gasiorowski, J.; Horban, A.; Prokopowicz, D.; Wiercinska-Drapalo, A.; Boron-Kaczmarska, A.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Antunes, F.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Babes, V.; Streinu-Cercel, A.; Vinogradova, E.; Rakhmanova, A.; Jevtovic, D.; Mokrás, M.; Staneková, D.; González-Lahoz, J.; Sanchez-Conde, M.; García-Benayas, T.; Martin-Carbonero, L.; Soriano, V.; Clotet, B.; Jou, A.; Conejero, J.; Ruiz, L.; Tural, C.; Gatell, J. M.; Miró, J. M.; Zamora, L.; Blaxhult, A.; Karlsson, A.; Pehrson, P.; Ledergerber, B.; Francioli, P.; Telenti, A.; Hirschel, B.; Soravia-Dunand, V.; Furrer, H.; Kravchenko, E.; Chentsova, N.; Fisher, M.; Brettle, R.; Barton, S.; Johnson, A. M.; Mercey, D.; Murphy, M.; Johnson, M. A.; Weber, J.; Scullard, G.; Morfeldt, L.; Thulin, G.; Akerlund, B.; Koppel, K.; Flamholc, L.; Håkangård, C.; Moroni, M.; Cargnel, A.; Merli, S.; Rizzardini, G.; Pastecchia, C.; Caggese, L.; Moioli, C.; Mura, M. S.; Mannazzu, M.; Suter, F.; Manconi, P. E.; Piano, P.; Lo Caputo, S.; Poggiom, A.; Bottari, G.; Pagano, G.; Alessandrini, A.; Scasso, A.; Vincenti, A.; Abbadessa, V.; Mancuso, S.; Alberici, F.; Ruggieri, A.; Arlotti, M.; Ortolani, P.; de Lalla, F.; Tositti, G.; Cassola, G.; Piscopo, R.; Raise, E.; Ebo, F.; Soscia, F.; Tacconi, L.; Tirelli, U.; Di Gennaro, G.; Santoro, D.; Pusterla, L.; Carosi, G.; Torti, C.; Cadeo, G.; Bertelli, D.; Carnevale, G.; Galloni, D.; Filice, G.; Bruno, R.; Di Perri, G.; Arnaudo, I.; Caramello, P.; Orofino, G. C.; Soranzo, M. L.; Bonasso, M.; Quirino, T.; Melzi, S.; Chiodo, F.; Colangeli, V.; Magnani, G.; Ursitti, M.; Menichetti, F.; Martinelli, C.; Mussini, C.; Ghinelli, F.; Sighinolfi, L.; Coronado, O.; Ballardini, G.; Rizzo, E.; Montroni, M.; Braschi, M. C.; Petrelli, E.; Cioppi, A.; Cauda, R.; de Luca, A.; Petrosillo, N.; Noto, P.; Bontempo, G.; Acinapura, A.; Antonucci, G.; de Longis, P.; Lichtner, M.; Pastore, G.; Ladisa, N.; Viglietti, R.; Piazza, M.; Nappa, S.; Abrescia, N.; de Marco, M.; Colomba, A.; Prestileo, T.; de Stefano, C.; La Gala, A.; Cosco, L.; Scerbo, A.; Grima, P.; Tundo, P.; Vecchiet, J.; D'Alessandro, M.; Grisorio, B.; Ferrara, S.; Caissotti, C.; Dellamonica, P.; Bentz, L.; Bernard, E.; de Salvador-Guillouet, F.; Durant, J.; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B.; Pugliese, P.; Rahelinirina, V.; Roger, P. M.; Vandenbos, F.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.; Bürgisser, Ph; Cattacin, S.; Cavassini, M.; Dubs, R.; Egger, M.; Elzi, L.; Erb, P.; Fischer, M.; Flepp, M.; Fontana, A.; Furrer, H. J.; Gorgievski, M.; Günthard, H.; Kaiser, L.; Kind, C.; Klimkait, Th; Lauper, U.; Opravil, M.; Paccaud, F.; Pantaleo, G.; Perrin, L.; Piffaretti, J. C.; Rudin, C.; Schmid, P.; Schüpbach, J.; Speck, R.; Trkola, A.; Vernazza, P.; Yerly, S.


    BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors

  12. Incremental diagnostic value of combined quantitative and qualitative parameters of magnetocardiography to detect coronary artery disease. (United States)

    Shin, Eun-Seok; Lam, Yat-Yin; Her, Ae-Young; Brachmann, Johannes; Jung, Friedrich; Park, Jai-Wun


    Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. This study sought to investigate the incremental diagnostic value of combined quantitative and qualitative parameters of MCG to detect coronary artery disease (CAD). Ninety six patients with suspected CAD who underwent coronary angiography were enrolled in the analysis to test the diagnostic accuracy of 2 MCG parameters (a quantitative parameter of the percent change of ST-segment fluctuation score and a qualitative parameter of non-dipole phenomenon). The best cut-off value for the percent change of ST-segment fluctuation score was -51.0%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.1, 73.9, 82.0, 79.1, and 77.4, in the percent change of ST-segment fluctuation score and 86.5, 84.8, 88.0, 86.7, and 86.3 in non-dipole phenomenon. The area under the curve of receiver-operating characteristics was 0.79 for the percent change of ST-segment fluctuation score and 0.86 for non-dipole phenomenon (pquantitative parameter of percent change of ST-segment fluctuation score in the detection of significant CAD. Furthermore, this study found that the incorporation of non-dipole phenomenon into the percent change of ST-segment fluctuation score significantly improved the diagnostic performance of CAD detection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Christensen, JK; Eugen-Olsen, Jesper; Sørensen, M


    No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain rea...... TTV viremia (Psuspected to be an opportunistic pathogen with an independent influence on HIV progression....

  14. Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection


    Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar


    Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection.

  15. West Nile virus meningitis in a patient with human immunodeficiency virus type 1 infection

    Directory of Open Access Journals (Sweden)

    D. Pilalas


    Full Text Available The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.

  16. [Zheng Classification in Chinese Medicine: from Its Integration with Disease Diagnosis to Clinical Effectiveness Assessment and Combinational New Drug Discovery]. (United States)

    Lv, Ai-ping


    As the core of traditional Chinese medicine theory, Zheng (syndrome, or pattern) classification will promote personalized medicine by changing the clinical diagnosis into a more precise mode when integrating Zheng classification with disease diagnosis approaches. The author adopted rheumatoid arthritis (RA) as a disease model, to explore the scientific fundamentals of Zheng classification based on disease diagnosis using systemic biological approaches and evidence-based medicine design, as well as developed novel approaches on the methodology of clinical effectiveness evaluation on Chinese medicine and R&D of combinational drugs design based on Fu Fang (Chinese herbal formula). Some unique research design and methods are herein introduced.

  17. Characterization of a Highly Pathogenic Molecular Clone of Feline Immunodeficiency Virus Clade C


    de Rozières, Sohela; Mathiason, Candace K.; Rolston, Matthew R.; Chatterji, Udayan; Edward A. Hoover; Elder, John H


    We have derived and characterized a highly pathogenic molecular isolate of feline immunodeficiency virus subtype C (FIV-C) CABCpady00C. Clone FIV-C36 was obtained by lambda cloning from cats that developed severe immunodeficiency disease when infected with CABCpady00C (Abbotsford, British Columbia, Canada). Clone FIV-C36 Env is 96% identical to the noninfectious FIV-C isolate sequence deposited in GenBank (FIV-Cgb; GenBank accession number AF474246) (A. Harmache et al.) but is much more diver...

  18. Liver-related deaths among persons infected with the human immunodeficiency virus: The D:A:D Study

    DEFF Research Database (Denmark)

    Weber, R; Sabin, CA; Friis-Møller, Nina


    BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver......-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death....... RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count...

  19. Liver-related deaths among persons infected with the human immunodeficiency virus: The D:A:D Study

    DEFF Research Database (Denmark)

    Weber, R; Sabin, CA; Friis-Møller, Nina


    -related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death......BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver....... RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count...

  20. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jolles S


    Full Text Available Stephen Jolles Department of Immunology, University Hospital of Wales, Cardiff, UK Abstract: Immunoglobulin (Ig-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg or subcutaneously (SCIg. While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20 has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. Keywords: enzyme facilitated IgG infusion, recombinant human hyaluronidase PH20, subcutaneous immunoglobulin, intravenous immunoglobulin, primary immunodeficiency disease

  1. Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set. (United States)

    Park, Ji Eun; Park, Bumwoo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun


    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  2. A Combination of Species Evenness and Functional Diversity Is the Best Predictor of Disease Risk in Multihost Communities. (United States)

    Chen, Lifan; Zhou, Shurong


    Although accumulated evidence has shown that biodiversity can play an important role in disease transmission and prevalence, it remains unclear how different measures of diversity based on taxonomy or function perform in predicting disease risk. In this article, we assess the relative ability of species richness, Shannon's evenness index, single functional traits, and several functional diversity metrics and their interactions to predict disease risk in both nonequilibrium and equilibrium communities simulated by a multihost epidemiological model. On the basis of generalized linear models and Akaike's information criterion, we found that Shannon's evenness index outperforms species richness as a single variable in explaining variation in disease risk, while the best combination consists of Shannon's evenness index and functional diversity. This study is, to our knowledge, the first to demonstrate the important role played by species evenness and functional diversity in accounting for variation in disease risk in multihost communities.

  3. Laparoscopic Surgical Treatment of Severe Obesity Combined with Gastroesophageal Reflux Disease: A Pilot Randomized Two-Arm Controlled Clinical Study (United States)

    Ospanov, Oral B.; Orekeshova, Akzhunis M.; Fursov, Roman A.; Yelemesov, Aset A.


    Obesity and gastroesophageal reflux disease (GERD) are serious medical, social, and economic problems of modern society. A pilot randomized two-arm controlled clinical study was conducted to compare laparoscopic plication of the greater gastric curvature combined with Nissen fundoplication (LFN+LGP) versus only Nissen fundoplication (LFN). The…

  4. Yeast supplementation reduced the immune and metabolic responses to a combined viral-bacterial respiratory disease challenge in feedlot heifers (United States)

    Two treatments were evaluated in commercial feedlot heifers to determine the effects of a yeast supplement on immune and metabolic responses to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (324 ± 19.2 kg BW) were selected and randomly assigned to one of two treat...

  5. Uso de ciclosporina 0,05% tópica no tratamento do olho seco de pacientes portadores do vírus HIV Topical cyclosporine 0.05% for the treatment of dry eye disease in patients infected with the human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Rodrigo de Pinho Paes Barreto


    Full Text Available OBJETIVO: O presente estudo comparou a eficácia do tratamento da síndrome do olho seco em pacientes infectados pelo HIV com suplementação lacrimal (carboximetilcelulose sódica 0,5% ou com suplementação lacrimal associada à terapia anti-inflamatória (carboximetilcelulose sódica 0,5% e ciclosporina 0,05%. MÉTODOS: Vinte pacientes portadores do vírus HIV provenientes do ambulatório de Infectologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro foram selecionados. O diagnóstico de síndrome do olho seco foi baseado no questionário para olho seco (Ocular Surface Disease Index - OSDI®, teste de Schirmer I, tempo de ruptura do filme lacrimal e coloração da superfície ocular com rosa bengala a 1%. Os pacientes foram distribuídos em dois grupos com dez pacientes (20 olhos e acompanhados durante seis meses. O grupo I foi tratado com colírio de carboximetilcelulose sódica 0,5% e o grupo II foi tratado com a associação de carboximetilcelulose sódica 0,5% e ciclosporina 0,05% tópica. RESULTADOS: Comparando os resultados no início e no final do tratamento, a associação com ciclosporina 0,05% mostrou-se superior (p PURPOSE: This study evaluates the use of topical cyclosporine 0.05% and sodium carboxymethylcellulose 0.5% for the treatment of dry eye disease in patients infected with the human immunodeficiency virus. METHODS: Twenty HIV-positive-patients were selected from the Department of Infectious Diseases of the Federal University of Rio de Janeiro Hospital. Dry eye diagnosis was based on a dry eye questionnaire (Ocular Surface Disease Index - OSDI®, Schirmer I test, break up time and 1% rose bengal staining of the ocular surface. The patients were divided into two groups with ten patients (20 eyes. Group I received sodium carboxymethylcellulose 0.5% drops and group II received sodium carboxymethylcellulose 0.5% drops and topical cyclosporine 0.05% for six months. RESULTS: Comparing

  6. Features of The Heart Remodeling in Patients with Chronic Obstructive Pulmonary Diseases, Combined with Coronary Heart Diseases

    Directory of Open Access Journals (Sweden)

    A.Yu. Ryabova


    Full Text Available The characteristics of heart remodeling in patients with chronic obstructive pulmonary diseases ( COPD, associated with coronary heart diseases (CHD were examined. The changes of structural and functional state of myocardium, intracardiac relationships with associated pathology were under study. The role of blood inflammatory cytokines (IL-6, IL-8, TNF-a and the level of cell adhesion molecules (ICAM-1, VCAM-1 in exacerbating myocardial dysfunction was clarified.

  7. Uveitis as an initial manifestation of acquired immunodeficiency syndrome. (United States)

    Tsen, Chui-Lien; Chen, Shih-Chou; Chen, Yao-Shen; Sheu, Shwu-Jiuan


    Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a multisystem disease that can involve the human eyes. Using ophthalmic examination records from January 2006 to November 2015, we retrospectively reviewed all patients who were diagnosed with HIV/AIDS in our hospital. The study was performed at a tertiary referral center in southern Taiwan. Data included age, gender, ophthalmic examinations, systemic conditions, CD4 cell counts, course, and treatment. Eleven patients were identified as having AIDS with uveitis as their presenting manifestation. All were men, with a mean age of 39.5 ± 11.4 years (range 24-56). The mean CD4 + T-cell counts were 91.7 ± 50.3 cells/μl (range 27-169). Ocular diagnoses included cytomegalovirus (CMV) retinitis in five patients, ocular syphilis in four patients, and ocular toxoplasmosis in two patients. Uveitis resolved in all patients after medical treatment. However, a retinal detachment developed in two eyes in CMV retinitis and one eye in ocular syphilis. Ocular manifestations are among the most common clinical features in patients with HIV/AIDS who have varying clinical presentations that affect almost all ocular structures. This study demonstrated that ocular findings could be an initial manifestation of an underlying disease. Awareness of ocular lesions in HIV/AIDS is important for early recognition and management.

  8. Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Funda Erol Çipe


    Full Text Available Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1 was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

  9. [Real world analysis to explore Xiyanping injection combined with other drugs for hand-foot-mouth disease]. (United States)

    Wang, Zhi-Fei; Fan, Hai-Wei; Xie, Yan-Ming


    Integrated network analysis was used in this paper to analyze Xiyanping injection combined therapy for hand-foot-mouth disease based on the registered research data of 3 204 cases. It was found that the drug combination therapy was almost consistent with the guidelines for the diagnosis and treatment of hand foot mouth disease, but there were some problems to be noticed: there were too many applications of antibiotics, more than the need in preventing secondary infection; and ribavirin was not necessary for use. This article showed that the clinical antibacterial and antiviral values of Xiyanping injection has not been well recognized for hand-foot-mouth disease. Copyright© by the Chinese Pharmaceutical Association.

  10. Comparison between Balloon Kyphoplasty and Short Segmental Fixation Combined with Vertebroplasty in the Treatment of Kümmell's Disease. (United States)

    Chen, Liang; Dong, Renbin; Gu, Yong; Feng, Yu


    Kümmell's disease is a clinical syndrome characterized by a minor spinal trauma with a symptom-free period from months to years, followed by progressive painful kyphosis. Kyphoplasty and vertebroplasty have been introduced to treat Kümmell's disease, and obtained good clinical results. Recently, delayed cement displacement was reported for Kümmell's disease treated by cement augmentation alone. Some authors recommended internal fixation combined with cement injection for this particular condition. To evaluate and compare the clinical efficacy, especially the pain reduction, of 2 procedures (kyphoplasty alone versus short segmental fixation combined with vertebroplasty) in the treatment of Kümmell's disease. Retrospective evaluation and comparison of postoperative VAS scores and radiographic outcomes. Single center inpatient population. Two procedures, including conventional balloon kyphoplasty and short segmental fixation combined with vertebroplasty, were utilized for 54 patients with Kümmell's disease. All patients were followed-up for 8-42 months. Visual analog scale (VAS), vertebral height, and local kyphotic angle were evaluated and compared for 2 groups before surgery, after surgery, and at final follow-up. Pearson correlation coefficients were calculated to assess the relationship between the decreased values of pain scores (VAS) and improvement of anterior vertebral height and local kyphotic angle. For the KP group, the VAS pain score decreased significantly from 7.8 ± 0.9 before surgery to 3.3 ± 1.0 after surgery (P kyphoplasty alone and short segmental fixation combined with vertebroplasty for Kümmell's disease were safe and effective. Improvement of VAS score had no correlation with improvement of vertebral height or local kyphotic angle. Comparatively, balloon kyphoplasty resulted in same the clinical outcomes with less complications.

  11. Mutation Analysis of Consanguineous Moroccan Patients with Parkinson’s Disease Combining Microarray and Gene Panel

    Directory of Open Access Journals (Sweden)

    Ahmed Bouhouche


    Full Text Available During the last two decades, 15 different genes have been reported to be responsible for the monogenic form of Parkinson’s disease (PD, representing a worldwide frequency of 5–10%. Among them, 10 genes have been associated with autosomal recessive PD, with PRKN and PINK1 being the most frequent. In a cohort of 145 unrelated Moroccan PD patients enrolled since 2013, 19 patients were born from a consanguineous marriage, of which 15 were isolated cases and 4 familial. One patient was homozygous for the common LRRK2 G2019S mutation and the 18 others who did not carry this mutation were screened for exon rearrangements in the PRKN gene using Affymetrix Cytoscan HD microarray. Two patients were determined homozygous for PRKN exon-deletions, while another patient presented with compound heterozygous inheritance (3/18, 17%. Two other patients showed a region of homozygosity covering the 1p36.12 locus and were sequenced for the candidate PINK1 gene, which revealed two homozygous point mutations: the known Q456X mutation in exon 7 and a novel L539F variation in exon 8. The 13 remaining patients were subjected to next-generation sequencing (NGS that targeted a panel of 22 PD-causing genes and overlapping phenotypes. NGS data showed that two unrelated consanguineous patients with juvenile-onset PD (12 and 13 years carried the same homozygous stop mutation W258X in the ATP13A2 gene, possibly resulting from a founder effect; and one patient with late onset (76 years carried a novel heterozygous frameshift mutation in SYNJ1. Clinical analysis showed that patients with the ATP13A2 mutation developed juvenile-onset PD with a severe phenotype, whereas patients having either PRKN or PINK1 mutations displayed early-onset PD with a relatively mild phenotype. By identifying pathogenic mutations in 45% (8/18 of our consanguineous Moroccan PD series, we demonstrate that the combination of chromosomal microarray analysis and NGS is a powerful approach to

  12. [Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection]. (United States)

    Aguirrebengoa, Koldo


    Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Immunotherapy of murine retrovirus-induced acquired immunodeficiency by CD4 T regulatory cell depletion and PD-1 blockade. (United States)

    Li, Wen; Green, William R


    LP-BM5 retrovirus induces a complex disease featuring an acquired immunodeficiency syndrome termed murine AIDS (MAIDS) in susceptible strains of mice, such as C57BL/6 (B6). CD4 T helper effector cells are required for MAIDS induction and progression of viral pathogenesis. CD8 T cells are not needed for viral pathogenesis, but rather, are essential for protection from disease in resistant strains, such as BALB/c. We have discovered an immunodominant cytolytic T lymphocyte (CTL) epitope encoded in a previously unrecognized LP-BM5 retroviral alternative (+1 nucleotide [nt]) gag translational open reading frame. CTLs specific for this cryptic gag epitope are the basis of protection from LP-BM5-induced immunodeficiency in BALB/c mice, and the inability of B6 mice to mount an anti-gag CTL response appears critical to the initiation and progression of LP-BM5-induced MAIDS. However, uninfected B6 mice primed by LP-BM5-induced tumors can generate CTL responses to an LP-BM5 retrovirus infection-associated epitope(s) that is especially prevalent on such MAIDS tumor cells, indicating the potential to mount a protective CD8 T-cell response. Here, we utilized this LP-BM5 retrovirus-induced disease system to test whether modulation of normal immune down-regulatory mechanisms can alter retroviral pathogenesis. Thus, following in vivo depletion of CD4 T regulatory (Treg) cells and/or selective interruption of PD-1 negative signaling in the CD8 T-cell compartment, retroviral pathogenesis was significantly decreased, with the combined treatment of CD4 Treg cell depletion and PD-1 blockade working in a synergistic fashion to substantially reduce the induction of MAIDS.

  14. Human immunodeficiency virus type 2: pathogenesis and antiretroviral therapy

    NARCIS (Netherlands)

    M.E. van der Ende (Marchina)


    textabstractHuman immunodeficiency virus type1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) have been identified as hither unknown primate members of the Lentivirinae subfamily of the family Retroviridae in 1983, 1986 and 1985 respectively, HIV-1

  15. Effect of decimeter range waves in combination with drug electroaerosols on immunoinflammatory processes during chronic nonspecific lung diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ayrapetova, N.S.; Tkachenko, A.F.

    An attempt was made to optimize the therapy of chronic nonspecific pulmonary diseases using a combination of decimeter range waves (DRW) and broncholytic electroaerosols. The electroaerosols penetrate rapidly deep into the lungs up to the aveoli, combining the action of an electric charge with the pharmaceutical effect. In all, 232 patients were studied (94.8% with chronic bronchitis, 5.2% with chronic pneumonia) manifesting an active inflammatory process, disturbance of the immune status and diminished glucocorticoid activity. After 15 procedures of combined therapy, 88.5% of the patients showed improvement in their clinical status; 65.4% of the control group (receiving only the electroaerosol) also showed improvement. In this combined therapy, the antiinflammatory and immunosuppressive effect were achieved due to the action of DRW; the electroaerosols had a positive effect on the function state of the cardiorespiratory system. 11 references.

  16. Combining anatomical, diffusion, and resting state functional magnetic resonance imaging for individual classification of mild and moderate Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Tijn M. Schouten


    Full Text Available Magnetic resonance imaging (MRI is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD, and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N=77 from the prospective registry on dementia study and controls (N=173 from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC of 0.760 (full correlations between functional networks to 0.909 (grey matter density. When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.

  17. Combining anatomical, diffusion, and resting state functional magnetic resonance imaging for individual classification of mild and moderate Alzheimer's disease. (United States)

    Schouten, Tijn M; Koini, Marisa; de Vos, Frank; Seiler, Stephan; van der Grond, Jeroen; Lechner, Anita; Hafkemeijer, Anne; Möller, Christiane; Schmidt, Reinhold; de Rooij, Mark; Rombouts, Serge A R B


    Magnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N = 77) from the prospective registry on dementia study and controls (N = 173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.

  18. Combining Public Health Education and Disease Ecology Research: Using Citizen Science to Assess Chagas Disease Entomological Risk in Texas.

    Directory of Open Access Journals (Sweden)

    Rachel Curtis-Robles


    Full Text Available Chagas disease is a zoonotic parasitic disease well-documented throughout the Americas and transmitted primarily by triatomine 'kissing bug' vectors. In acknowledgment of the successful history of vector control programs based on community participation across Latin America, we used a citizen science approach to gain novel insight into the geographic distribution, seasonal activity, and Trypanosoma cruzi infection prevalence of kissing bugs in Texas while empowering the public with information about Chagas disease.We accepted submissions of kissing bugs encountered by the public in Texas and other states from 2013-2014 while providing educational literature about Chagas disease. In the laboratory, kissing bugs were identified to species, dissected, and tested for T. cruzi infection. A total of 1,980 triatomines were submitted to the program comprised of at least seven species, of which T. gerstaeckeri and T. sanguisuga were the most abundant (85.7% of submissions. Triatomines were most commonly collected from dog kennels and outdoor patios; Overall, 10.5% of triatomines were collected from inside the home. Triatomines were submitted from across Texas, including many counties which were not previously known to harbor kissing bugs. Kissing bugs were captured primarily throughout April-October, and peak activity occurred in June-July. Emails to our dedicated account regarding kissing bugs were more frequent in the summer months (June-August than the rest of the year. We detected T. cruzi in 63.3% of tested bugs.Citizen science is an efficient approach for generating data on the distribution, phenology, and infection prevalence of kissing bugs-vectors of the Chagas disease parasite-while educating the public and medical community.

  19. Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk

    DEFF Research Database (Denmark)

    Franklin, J G; Paus, M D; Pluetschow, A


    Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking.......Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking....

  20. Umeclidinium bromide/vilanterol combination in the treatment of chronic obstructive pulmonary disease: a review


    Spyratos, Dionisios; Sichletidis, Lazaros


    Dionisios Spyratos, Lazaros Sichletidis Pulmonary Department, “G Papanikolaou” Hospital, Aristotle University of Thessaloniki, Exohi, Thessaloniki, Greece Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease among the elderly that could be prevented by smoking cessation. As it is characterized by airflow limitation that is not fully reversible, bronchodilator therapy is the first choice of treatment. Symptomatic COPD patients with ...

  1. Mathemical models of molecular epidemiology : Combining genetic and epidemiological data to unravel infectious disease dynamics

    NARCIS (Netherlands)

    Ypma, R.J.F.


    To prevent infectious diseases from spreading, it is often very valuable to know how, when, where and between whom transmissions occur: the dynamics of the disease. These dynamics can be quantified using observations of illness, such as time of symptom onset. A relatively new source of information

  2. A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B


    Full Text Available Abstract Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919 in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969. The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803 effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.

  3. Human Immunodeficiency Virus Related Knowledge, Risk ...

    African Journals Online (AJOL)

    University, Kaski, Nepal,3Jawaharlal Nehru Medical College, KLE University, Belgaum, Karnataka, India, 5Department of. Obstetrics and Gynecological Nursing, Institute of Nursing science, KLE University, Belgaum, Karnataka, India. Abstract. Background: Despite the implementation of anti‑human immunodeficiency virus ...

  4. Tools for genotyping human immunodeficiency virus, and ...

    African Journals Online (AJOL)



    Dec 29, 2008 ... Janini LM, Tanuri A, Schechter M, Peralta JM, Vicente AC, Dela Torre. N, Pieniazek NJ, Luo CC, Ramos A, Soriano V, Schochetman G,. Rayfield MA, Pieniazek D (1998). Horizontal and vertical transmission of human immunodeficiency virus type 1 dual infections caused by viruses of subtypes B and C. J ...

  5. Nigerian dental technology students and human immunodeficiency ...

    African Journals Online (AJOL)

    Background: The rehabilitative dental care is important for maintaining adequate nutrition, guarding against wasting syndrome and malnutrition among human immunodeficiency virus (HIV)‑infected individuals. Aim: The aim of this study is to determine the Nigerian dental technology students' knowledge and ...

  6. Seroprevalence of Helicobacter pylori in human immunodeficiency ...

    African Journals Online (AJOL)

    Background: This study assessed the seroprevalence of Helicobacter pylori antibodies among Iranian patients with human immunodeficiency virus (HIV) infection. It also examines whether anti H. pylori seroprevalence was associated with the severity of the HIV infection or the antiretroviral treatment. Material and Methods: ...

  7. Human Immunodeficiency Virus Infection among Psychiatric ...

    African Journals Online (AJOL)

    Background: Psychiatric patients are considered high risked group for Human immunodeficiency virus (HIV) infection. This has been found to be as a result of poor judgment and irrationality associated with some of the disorders. However, there is dearth of literature on the prevalence of HIV infection among psychiatric ...

  8. Ethnopharmacology of human immunodeficiency virus in South ...

    African Journals Online (AJOL)

    Infection with the human immunodeficiency virus (HIV), the etiologic agent of acquired immune deficiency syndrome (AIDS), continues to pose an unprecedented public health problem of enormous proportions worldwide. Current treatment options for HIV/AIDS have not been satisfactory and the quest for effective curative or ...

  9. Clinical characteristics of Human Immunodeficiency Virus (HIV ...

    African Journals Online (AJOL)

    Renal failure is a common finding in human immunodeficiency virus infected patients, and it contributes significantly to their morbidity and mortality. Most dialysis centres in Nigeria currently do not accept HIV positive patients for dialysis therapy for many reasons. The prevailing high level of stigmatization of HIV positive ...

  10. Dental Practice, Human Immunodeficiency Virus Transmission and ...

    African Journals Online (AJOL)

    The acquired immune deficiency syndrome (AIDS) is a major cause of death in Africa today and it is estimated that 80% of the over 40 million people living with human immunodeficiency virus (HIV)/AIDS (PLWHA) world-wide are residing in sub-Saharan countries.[1] In Nigeria, AIDS was first reported in 1986 following the ...

  11. Mitochondrial dysfunction and human immunodeficiency virus ...

    African Journals Online (AJOL)

    Human immunodeficiency virus (HIV) infection and the pharmacological treatment thereof have both been shown to affect mitochondrial function in a number of tissues, and each may cause specific organ pathology through specific mitochondrial pathways. HIV has been shown to kill various tissue cells by activation of ...

  12. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B ...

    African Journals Online (AJOL)

    Gonçales FL Jr, Pereira JS, Da Silva C, Thomaz GR, Pavan MH,. Fais VC, et al. Hepatitis B virus DNA in sera of blood donors and of patients infected with hepatitis C virus and human immunodeficiency virus. Clin Diagn Lab Immunol. 2003;10:718‑20. 25. Bahaf F, Tanomand A, Montazam H, Sany AA. Seroprevalence.

  13. Attitudes of patients towards voluntary human immunodeficiency ...

    African Journals Online (AJOL)

    Attitudes of patients towards voluntary human immunodeficiency virus counselling and testing in two Nigerian tertiary hospitals. ... Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download ...

  14. Human Immunodeficiency Virus Infection Occupational Post ...

    African Journals Online (AJOL)


    potentially infected body fluids so that they can present themselves rapidly for risk assessment and commencement of ART if necessary in the event of an occupational exposure to HIV. INTRODUCTION. Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immune Deficiency Syndrome. (AIDS). It can be ...

  15. Human immunodeficiency virus infection among migrant fishermen ...

    African Journals Online (AJOL)

    Background: People migrate from place to place for diverse reasons chief among which is economic. Migrant fishermen like other migrant population lead high risk sexual lifestyle and are therefore, predisposed to Human immunodeficiency virus (HIV) infection. Aim: To determine the prevalence of HIV among migrant ...

  16. Acquired immunodeficiency syndrome with subacute sclerosing panencephalitis. (United States)

    Gowda, Vykuntaraju K N; Sukanya, V; Shivananda


    A 7-year-old boy with acquired immunodeficiency syndrome, receiving antiretroviral drugs for 2 years, presented with a recent onset of myoclonic jerks and cognitive deterioration. On examination, he manifested myoclonic jerks once every 10-15 seconds. His electroencephalogram indicated periodic complexes, and his cerebrospinal fluid tested positive for measles antibodies. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Newborn screening for severe primary immunodeficiencies


    Borte, Stephan


    Primary immunodeficiencies (PID) are congenital disorders of immune competence, which are mainly characterized by a pathological susceptibility to infection. This is often accompanied by severe recurrent infections with drug-resistant, long progressions. In addition, there are associated immune regulation disorders, which may manifest themselves in granuloma formation, autoimmunity, recurrent fever, eczema, lymphoproliferation and chronic intestinal inflammation. More than 240 ...

  18. Post exposure prophylaxis against human immunodeficiency virus ...

    African Journals Online (AJOL)

    Objective: To determine the level of awareness, knowledge and practice of human immunodeficiency virus post exposure prophylaxis (HIV PEP) among paediatricians in Nigeria. Methodology: The study was a cross sectional questionnairebased survey conducted among paediatrcians that attended the Paediatric ...

  19. Comparative periodontal status of human immunodeficiency virus ...

    African Journals Online (AJOL)

    Background: There are diverse reports on the prevalence and severity of chronic periodontitis in human immunodeficiency virus (HIV) positive persons. Few studies have been carried out in developing countries in Sub.Saharan Africa. This study was aimed at comparing the prevalence and severity of chronic periodontitis of ...

  20. Haematological Changes in Human immunodeficiency Virus ...

    African Journals Online (AJOL)

    Haematological Changes in Human immunodeficiency Virus Infected Pregnant Women in Benin City, Nigeria. ... A differential leucocyte count was also done by the thin blood film method, stained with Leishman stain and examined microscopically. The erythrocyte sedimentation rate (ESR) was carried out using the


    African Journals Online (AJOL)

    ABSTRACT. A seroprevalence study of Human immunodeficiency virus (HIV) infection in new patients attending the eye clinic of LAUTECH. Teaching Hospital in Osogbo, Osun State, Nigeria showed that twenty-nine patients 2.7%) were positive to HIV1. No patient was positive to HIV 2. There were 21 males (72.4%) and 8 ...

  2. Treatment Outcomes among Human Immunodeficiency Virus and ...

    African Journals Online (AJOL)

    The complex interactions between Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) infections may be magnified, in the presence of another potentially stressful condition like pregnancy. Though co-infection among pregnant women is rare, treatment outcomes may depend on accessibility to comprehensive ...

  3. Primary immunodeficiencies and B-cell lymphomas. (United States)

    Martín-Mateos, María Anunciación; Piquer Gibert, Mónica

    In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  4. Disease: H01244 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01244 T+B+Severe combined immunodeficiencies (SCIDs) Recently, several groups reported a novel clinic...nsion of TCR-gamma/delta T cells combined with TCR-alpha/beta T cell lymphopenia. The clinic

  5. Disease: H01244 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01244 T+B+Severe combined immunodeficiencies (SCIDs) Recently, several groups reported a novel clinica...ansion of TCR-gamma/delta T cells combined with TCR-alpha/beta T cell lymphopenia. The clinica

  6. Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome: a paradigm of immunodeficiency with autoimmunity

    Directory of Open Access Journals (Sweden)

    Federica eBarzaghi


    Full Text Available Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome is a rare monogenic primary immunodeficiency (PID due to mutations of FOXP3, a key transcription factor for naturally occurring (n regulatory T (Treg cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type 1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia, can develop in patients who survive the initial acute phase.The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is haematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease.This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

  7. Serial observations of chronic rotavirus infection in an immunodeficient child. (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H


    Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host.

  8. Cutaneous Manifestations of Human Immunodeficiency Virus Infection in Taiwan

    Directory of Open Access Journals (Sweden)

    Tien-Yi Tzung


    Full Text Available Cutaneous manifestations are common and often the presenting feature of human immunodeficiency virus (HIV infection, but a comprehensive study of HIV-associated skin lesions is not available in Taiwan. We reviewed all skin lesions in all HIV patients diagnosed in our department between 1990 and 1998 to document the spectrum of skin manifestations, the frequency of each disorder, and their relationship with CD4 counts. A total of 64 HIV patients were studied, including 38 with acquired immunodeficiency syndrome (AIDS (CD4 < 200 × 106 cells/L and 26 who had not developed AIDS (non-AIDS. There were 142 episodes of skin conditions representing 25 different skin diseases, including oral candidiasis (15% in non-AIDS vs 71% in AIDS patients, drug eruptions, herpes simplex, seborrheic dermatitis, dermatophytosis, herpes zoster, secondary syphilis, condyloma acuminatum, Kaposi's sarcoma (16% among AIDS patients, hairy leukoplakia, and molluscum contagiosum (13% among AIDS patients, in decreasing order. Several unusual cases are briefly described, including verrucous herpes infection, condyloma-like molluscum contagiosum, and AIDS-associated pigmented erythroderma. In our study, 70% of all HIV patients had skin diseases, with an average of 2.2 conditions per patient (3.2 in AIDS patients vs 0.7 in non-AIDS patients; p < 0.001. A broad spectrum of HIV-associated skin diseases was observed in our series. The frequency of HIV-associated skin disease was 92% in AIDS patients and 39% in non-AIDS patients; 78% of skin lesions in AIDS patients were diagnosed when CD4 counts were below 100 × 106 cells/L.

  9. Combined Dietary Nitrate and Exercise Intervention in Peripheral Artery Disease: Protocol Rationale and Design. (United States)

    Woessner, Mary N; VanBruggen, Mitch D; Pieper, Carl F; O'Reilly, Erin K; Kraus, William E; Allen, Jason D


    Peripheral artery disease (PAD) is caused by atherosclerotic occlusions in the legs. It affects approximately 8-12 million people in the United States alone, one-third of whom suffer from intermittent claudication (IC), defined as ischemic leg pain that occurs with walking and improves with rest. Patients with IC suffer a markedly impaired quality of life and a high perception of disability. Improving pain-free walking time is a primary goal of rehabilitation in this population. The nitric oxide (NO)-PAD trial is designed to compare the effects that 12 weeks of supervised exercise training, in combination with a high inorganic nitrate-content (beetroot [BR] juice) beverage or placebo (PL) beverage, has on clinical outcomes of exercise and functional capacity in two groups of PAD+IC patients: exercise training plus beetroot (EX+BR) and exercise training plus placebo (EX+PL). The primary aims of this randomized controlled, double-blind pilot study are to determine group differences following 12 weeks of EX+BR versus EX+PL in the changes for (1) exercise capacity: pain-free walking time (claudication onset time, COT), peak walk time (PWT), and maximal exercise capacity (peak oxygen uptake, VO2peak) during a maximal-graded cardiopulmonary exercise test (max CPX) and (2) functional capacity: 6-minute walk (6MW) distance. The secondary aims will provide mechanistic insights into the exercise outcome measures and will include (1) gastrocnemius muscle oxygenation during exercise via near-infrared spectroscopy (NIRS); (2) gastrocnemius muscle angiogenesis: capillaries per unit area and per muscle fiber, and relative fraction of type I, IIa, IIb, and IId/x fibers; and (3) vascular health/function via brachial artery flow-mediated dilation, lower-limb blood flow via plethysmography, and pulse wave velocity and reflection. A total of 30 subjects between 40 and 80 years of age with PAD who are limited by IC will undergo exercise training 3 days per week for 12 weeks (ie, 36

  10. Mathematical models of SIR disease spread with combined non-sexual and sexual transmission routes


    Joel C. Miller


    The emergence of Zika and Ebola demonstrates the importance of understanding the role of sexual transmission in the spread of diseases with a primarily non-sexual transmission route. In this paper, we develop low-dimensional models for how an SIR disease will spread if it transmits through a sexual contact network and some other transmission mechanism, such as direct contact or vectors. We show that the models derived accurately predict the dynamics of simulations in the large population limi...

  11. Equine diseases caused by known genetic mutations. (United States)

    Finno, Carrie J; Spier, Sharon J; Valberg, Stephanie J


    The recent development of equine genome maps by the equine genome community and the complete sequencing of the horse genome performed at the Broad Institute have accelerated the pace of genetic discovery. This review focuses on genetic diseases in the horse for which a mutation is currently known, including hyperkalemic periodic paralysis, severe combined immunodeficiency, overo lethal white syndrome, junctional epidermolysis bullosa, glycogen branching enzyme deficiency, malignant hyperthermia, hereditary equine regional dermal asthenia, and polysaccharide storage myopathy. Emphasis is placed on the prevalence, clinical signs, etiology, diagnosis, treatment and prognosis for each disease.

  12. Human immunodeficiency virus and anaesthesia

    African Journals Online (AJOL)

    disease process, and may or may not be on antiretroviral therapy (ART). This article will concentrate mainly on ... Recurrent or chronic upper respiratory tract infections, such as otitis media, otorrhoea, sinusitis, or tonsillitis .... Impair Vitamin D metabolism, leading to osteoporosis. • The effects of midazolam and diazepam are.

  13. Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson’s Disease Patients

    Directory of Open Access Journals (Sweden)

    U. Hidding


    Full Text Available The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN and combined subthalamic nucleus and substantia nigra (STN+SNr high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: 61.3±7.3 years; disease duration: 12.3±5.4 years; Hoehn and Yahr stage: 2.2±0.39 were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS, Modified Fatigue Impact Scale (MFIS, Becks Depression Inventory (BDI-I, Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS, and Parkinson’s Disease Questionnaire (PDQ-39. Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

  14. The efficacy of infliximab combined with surgical treatment of fistulizing perianal Crohn's disease: Comparative analysis according to fistula subtypes. (United States)

    Park, Eun Jung; Song, Ki-Hwan; Baik, Seung Hyuk; Park, Jae Jun; Kang, Jeonghyun; Lee, Kang Young; Goo, Ja Il; Kim, Nam Kyu


    Infliximab is regarded as an effective therapeutic to treat Crohn's disease. This study aimed to assess the efficacy of infliximab combined with surgery and to analyze clinical manifestations according to fistula subtypes in patients with fistulizing perianal Crohn's disease. From April 2013 to December 2015, 47 patients with perianal Crohn's disease in two hospitals of South Korea (Goo Hospital, Gangnam Severance Hospital) were evaluated retrospectively. Patients were categorized into two groups as simple fistula (n = 20) and complex fistula group (n = 27). All patients received 5 mg/kg of infliximab intravenously at 0, 2, and 6 weeks after surgical treatments. Then every eight weeks, the responders continued to receive 5 mg/kg infliximab for maintenance therapy. Complete response of induction therapy was 72.3%, and partial response was 27.7%. After maintenance therapy, complete response was 97.9% and partial response was 2.1%. There was no patient without a response to infliximab in this study. The median time to the first fistula closure was 6.00 ± 8.00 weeks. Infliximab was used on average 2.13 ± 0.71 times until the first fistula closure. The rate of recurrence was 8.5% and adverse events were 4.2%. In comparison with clinical manifestations between simple and complex fistula groups, there was no significant difference except for the coexistence of perianal abscess. Combined surgical and infliximab therapy was efficacious to treat fistulizing perianal Crohn's disease with rapid treatment response and favorable clinical outcomes. It is expected that this top-down strategy with combining surgeries can overcome previous limitations in treating perianal Crohn's disease. Copyright © 2017. Published by Elsevier Taiwan.

  15. Overweight and obesity in children with congenital heart disease: combination of risks for the future? (United States)

    Barbiero, Sandra Mari; D'Azevedo Sica, Caroline; Schuh, Daniela Schneid; Cesa, Claudia Ciceri; de Oliveira Petkowicz, Rosemary; Pellanda, Lucia Campos


    Children who have unhealthy lifestyles are predisposed to develop hypertension, dyslipidemia and other complications. The epidemic of obesity is also affecting children with congenital heart disease. The aim of this study is to estimate the prevalence of obesity and describe associated risk factors, including family history in children with congenital heart disease. A cross-sectional study with 316 children and adolescents with congenital heart disease seen in an outpatient clinic of a reference hospital. Collected sociodemographic data included family history of chronic disease, dietary habits, laboratory tests (total cholesterol, HDL and LDL/cholesterol, triglycerides, fasting glucose, CRP, hematocrit and hemoglobin), and anthropometric assessment. Anthropometric data of the caregivers was self-reported. The prevalence of excess weight was 26.9%. Altered levels of total cholesterol were observed in 46.9%, of HDL in 32.7%, LDL in 23.6% and of triglycerides levels in 20.0%. A higher frequency of family history of obesity (42.6%; p = 0.001), dyslipidemia (48.1%; p = disease (43.7%; p = 0.023), as well as significantly higher values of triglycerides (p = 0.017), glycemia (p = 0.004) and C-reactive protein (p = 0.002) were observed among patients with excess weight. The presence of modifiable risk factors and the variables associated to excess weight in this population was similar to that described in the literature for children without congenital disease. As these children already present the risks associated to heart disease, it is particularly important to promote a healthy lifestyle in this group.

  16. [A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats]. (United States)

    Kashkin, V A; Shekunova, E V; Makarova, M N; Makarov, V G

    To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson's disease in rats. Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed. Combined therapy led to the decrease in muscle rigidity (the decrease of gibbosity in resistance to passive flexion in the ankle joint). There was a decrease in oligokinesia that emerged in higher vertical and horizontal locomotor activity of experimental animals, decrease in the time of head turning during climbing down the pole and total time of climbing down the pole. The combination of drugs had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy.

  17. Disease: H00090 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00090 NK cell defects, including the following disease: CD16 deficiency A patient...Current perspectives on primary immunodeficiency diseases. ... JOURNAL ... Clin Dev Immunol 13:223-59 (2006) DOI:10.1080/17402520600800705 ...

  18. Efficacy and Tolerability of a Combination Treatment of Memantine and Donepezil for Alzheimer’s Disease: A Literature Review Evidence (United States)

    Riverol, Mario; Slachevsky, Andrea; López, Oscar L.


    INTRODUCTION Two types of drugs have been approved for the symptomatic treatment of Alzheimer’s disease (AD): the cholinesterase inhibitors (ChEIs) and memantine. There is a growing interest to know whether the combination of these drugs is safe and if it adds any clinical benefit to patients. OBJECTIVE To systematically review published medical literature assessing the efficacy and tolerability of a combination treatment of memantine and donepezil in AD patients. METHODS We searched PubMed for English and Spanish-language literature, using the terms “Alzheimer’s disease,” “cholinesterase inhibitors,” “donepezil,” and “memantine.” Our review focused on clinical trials and observational studies. RESULTS Eleven publications representing seven unique studies were selected for this review. Three were randomized double-blind, placebo-controlled trials and four were observational studies. CONCLUSIONS Available data revealed that the combination of memantine and donepezil slowed down cognitive decline, prolonged functional independence, and improved behavioral symptoms in patients with moderate to severe AD. The long-term use of the dual therapy decreased the risk of nursing home admission. More longitudinal studies are needed to further examine the role of combined therapy in the management of AD patients. PMID:25302109

  19. Parental consanguinity and the risk of primary immunodeficiency disorders: report from the Kuwait National Primary Immunodeficiency Disorders Registry. (United States)

    Al-Herz, Waleed; Naguib, Kamal K; Notarangelo, Luigi D; Geha, Raif S; Alwadaani, Amal


    It is proposed that consanguineous marriages increase the risk of primary immunodeficiency disorders (PID). The aim of this study is to review the frequency and pattern of parental consanguinity among PID patients and to determine its effects on the distribution of different PID, the patients' performance status and the risk of death. The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. The coefficient of inbreeding was determined for each patient and the patients' overall performance status was assessed using the Lansky Play Performance Scale and the Karnofsky Performance Scale. A total of 128 patients with PID from 99 families are reported. A family history suggestive of PID and parental consanguinity was reported in 44 and 75% of the patients respectively, while the mean coefficient of inbreeding was 0.044067. There were statistically significant associations between both a family history of PID and parental consanguinity and PID category, the risk of death and the patients' overall performance status. Evidence of autosomal recessive transmission of disease was present in 44% of the patients. Parental consanguinity is a risk factor for the development of PID. There is a need to increase the public awareness of the health consequences of consanguineous marriages. Copyright © 2010 S. Karger AG, Basel.

  20. The combination of stem cells and tissue engineering: an advanced strategy for blood vessels regeneration and vascular disease treatment. (United States)

    Wang, Ying; Yin, Pei; Bian, Guang-Liang; Huang, Hao-Yue; Shen, Han; Yang, Jun-Jie; Yang, Zi-Ying; Shen, Zhen-Ya


    Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient's condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.