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  1. Article ; Online: Non-surgical management in children with non-refluxing primary megaureter: a systematic review and meta-analysis.

    Buder, Kathrin / Opherk, Kathrin / Mazzi, Sara / Rohner, Katharina / Weitz, Marcus

    Pediatric nephrology (Berlin, Germany)

    2023  Volume 38, Issue 11, Page(s) 3549–3558

    Abstract: Background: Children with non-refluxing primary megaureter are mostly managed by a watchful approach with close follow-up and serial imaging.: Objectives: This systematic review and meta-analysis aimed to determine whether there is sufficient ... ...

    Abstract Background: Children with non-refluxing primary megaureter are mostly managed by a watchful approach with close follow-up and serial imaging.
    Objectives: This systematic review and meta-analysis aimed to determine whether there is sufficient evidence to support the current non-surgical management strategy in these patients.
    Data sources: A comprehensive search including electronic literature databases, clinical trial registries, and conference proceedings was performed.
    Data synthesis methods: Outcomes were estimated as pooled prevalence. If meta-analytical calculations were not appropriate, outcomes were provided in a descriptive manner.
    Results: Data from 8 studies (290 patients/354 renal units) were included. For the primary outcome, differential renal function estimated by functional imaging, meta-analysis was impossible due to reported data not being precise. Pooled prevalence for secondary surgery was 13% (95% confidence interval: 8-19%) and for resolution 61% (95% confidence interval: 42-78%). The risk of bias was moderate or high in most studies.
    Limitations: This analysis was limited by the low number of eligible studies with few participants and high clinical heterogeneity, and the poor quality of the available data.
    Conclusions: The low pooled prevalence of secondary surgical intervention and high pooled prevalence of resolution may support the current non-surgical management in children with non-refluxing primary megaureter. However, these results should be interpreted cautiously due to the limited available body of evidence. Future studies should overcome existing limitations of imaging methods by using standardized, comparable criteria and report outcome parameters in a quantitative manner. This would allow more sufficient data synthesis to provide evidence-based recommendations for clinical decision-making and counseling.
    Systematic review registration: The protocol was registered on PROSPERO under CRD42019134502.
    MeSH term(s) Humans ; Child ; Kidney Function Tests ; Kidney
    Language English
    Publishing date 2023-03-30
    Publishing country Germany
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-023-05938-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Conference proceedings: Adoptiver T-Zelltransfer als Therapieoption bei refraktären Virusinfektionen mit Adenovirus nach allogener Stammzelltransplantation

    Feucht, J. / Opherk, K. / Kayser, S. / Handgretinger, R. / Lang, P. / Feuchtinger, T.

    2013  , Page(s) 13dgpi01

    Event/congress 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI); Würzburg; Deutsche Gesellschaft für Pädiatrische Infektiologie; 2013
    Keywords Medizin, Gesundheit
    Publishing date 2013-03-28
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/13dgpi01
    Database German Medical Science

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  3. Article ; Online: Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort.

    Krägeloh-Mann, I / Groeschel, S / Kehrer, C / Opherk, K / Nägele, T / Handgretinger, R / Müller, I

    Bone marrow transplantation

    2012  Volume 48, Issue 3, Page(s) 369–375

    Abstract: Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history ... ...

    Abstract Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history is practically missing. We compare a girl with juvenile MLD 10 years after allogeneic HSCT not only with her untreated sister, but also with a large cohort of untreated patients. The girl received HSCT at the age of 5 years when first motor signs appeared. Over 10 years she was stable with respect to her clinical course and gained cognitive abilities. Magnetic resonance imaging (MRI) showed clear regression of white matter changes and magnetic resonance spectroscopy (MRS) demonstrated a reversal of the initial choline increase and N-acetyl-aspartate (NAA) decrease. Only axonal demyelinating neuropathy showed some progression. Her gross motor function and MRI-scores were clearly better compared with her sister and the cohort of untreated patients. Difference to her sister became apparent only 4 years after HSCT. We conclude that HSCT, early in the course of disease, can lead to stabilization of juvenile MLD with a course clearly different from the natural history. HSCT may prevent disease progression, if performed sufficient time before loss of walking, which typically initiates rapid deterioration.
    MeSH term(s) Adolescent ; Cohort Studies ; Disease Progression ; Female ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukodystrophy, Metachromatic/diagnosis ; Leukodystrophy, Metachromatic/pathology ; Leukodystrophy, Metachromatic/surgery ; Male ; Treatment Outcome
    Language English
    Publishing date 2012-09-03
    Publishing country England
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/bmt.2012.155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Conference proceedings: Clinical course of two siblings with Metachromatic Leukodystrophy (MLD) with and without Stem cell transplantation (SCT)

    Kehrer, C / Opherk, K / Müller, I / Wilke, M / Krägeloh-Mann, I

    Neuropediatrics

    2009  

    Abstract: Efficiency of invasive therapies needs proof, e.g. by comparison with the natural course of the treated disease. Affected siblings with similar manifestation offer the possibility to study this. We report on two sisters with juvenile MLD, the elder of ... ...

    Event/congress Abstracts of the 35th Annual Meeting of the Society of Neuropediatrics, Graz, 2009
    Abstract Efficiency of invasive therapies needs proof, e.g. by comparison with the natural course of the treated disease. Affected siblings with similar manifestation offer the possibility to study this. We report on two sisters with juvenile MLD, the elder of whom developed a groß motor coordination problems at the age of 5 years (y). Gait disorder, weakness and fine motor problems presented at the age of 6 y. MLD was diagnosed at the age of 8 y. Thereafter, groß motor function rapidly deteriorated (at 10 y of age loss of the ability to walk freely, at just under 11 y of age loss of the ability to sit and to grip, at 11 y of age loss of head control). Active speech also deteriorated. In the 6 years younger sister, MLD was preclinically diagnosed at the of 2 y. At the age of 4 9/12 y, she also developed groß motor coordination problems and weakness of the legs. Stem cell transplantation (SCT) was performed shortly before the age of 5 y. At that time, MRI scans already showed typical leukodystrophic alterations, and nerve conduction velocities (NCV) were reduced. MRI alterations were described with the use of a modified Loes-Score, the score remained stable after SCT. NCV also remained unchanged. ASA activity in leukocytes was normal after SCT, while sulfatide excretion in urine persisted. Cognitive development was documented by standardized tests (K-ABC) and school reports. Today, the 12 years old girl participates in sports and attends a secondary school. Gross motor function was described with the use of a modified GMFCS (Gross Motor Function Classification System) and remained stable since SCT. There was a rapid deterioration of groß motor function in the older sister, in whom SCT was not performed. SCT in patients with a juvenile MLD at a preclinical stage or at a stage with only mild symptoms seems to be a therapeutic option.
    Language English
    Publishing date 2009-04-07
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 573291-8
    ISSN 1439-1899 ; 0174-304X
    ISSN (online) 1439-1899
    ISSN 0174-304X
    DOI 10.1055/s-0029-1215804
    Database Thieme publisher's database

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  5. Article ; Online: Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific T(helper) cell response.

    Feuchtinger, Tobias / Opherk, Kathrin / Bicanic, Oliver / Schumm, Michael / Grigoleit, Götz Ulrich / Hamprecht, Klaus / Jahn, Gerhard / Handgretinger, Rupert / Lang, Peter

    Cytotherapy

    2010  Volume 12, Issue 7, Page(s) 945–950

    Abstract: Background aims: In the absence of a protective immune response, human cytomegalovirus (HCMV) infection remains a life-threatening complication after allogeneic stem cell transplantation (SCT), especially in recipients of grafts from HCMV-seronegative ... ...

    Abstract Background aims: In the absence of a protective immune response, human cytomegalovirus (HCMV) infection remains a life-threatening complication after allogeneic stem cell transplantation (SCT), especially in recipients of grafts from HCMV-seronegative donors. After allogeneic SCT from a seronegative donor, prolonged and severe immune deficiency often leads to infectious complications. Vaccination with antigen-loaded dendritic cells (DC) has been shown to be a potent approach for the induction of antigen-specific cytotoxic T-cell responses in vivo. For protection from subsequent HCMV reactivation, a sustained immune response is necessary, including antigen-specific CD4(+) T cells.
    Methods: We report the case of an 18-year-old girl with high-risk acute lymphoblastic leukemia that received an allogeneic SCT in CR2. After an HCMV infection, the graft was rejected and she received a second transplant from an HLA-mismatched, HCMV-seronegative family donor. She was treated with pp65-pulsed monocyte-derived DC at day 200 post-SCT, using a recombinant pp65 protein. Until day 200 post-SCT, HCMV reactivated six times with emerging viral resistance to antiviral chemotherapy.
    Results: After vaccination with protein-pulsed DC, an induction and expansion of HCMV-specific T(helper) cells and cytotoxic T lymphocytes was observed, associated with a sustained clearance of the HCMV viremia. Antiviral treatment could be tapered without recurrence of viremia within the first year post-SCT.
    Conclusions: pp65-pulsed DC could induce antigen-specific T-cell responses even after a SCT from an HCMV-seronegative donor. After vaccination with pp65-pulsed DC, a sustained antigen-specific T-cell response prevented concurrent HCMV viremia. Emergence of antigen-specific T(helper) cells may be essential for a sustained, functional T-cell response post-SCT.
    MeSH term(s) Adolescent ; Antibodies, Viral/blood ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/blood ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/physiopathology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Female ; Humans ; Lymphocyte Activation ; Phosphoproteins/immunology ; Stem Cell Transplantation ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; T-Lymphocytes, Cytotoxic/pathology ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Helper-Inducer/pathology ; Tissue Donors ; Vaccination ; Viral Matrix Proteins/immunology ; Viremia/prevention & control
    Chemical Substances Antibodies, Viral ; Phosphoproteins ; Viral Matrix Proteins ; cytomegalovirus matrix protein 65kDa
    Language English
    Publishing date 2010-11
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.3109/14653241003587645
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  6. Article ; Online: Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT.

    Feucht, Judith / Opherk, Kathrin / Lang, Peter / Kayser, Simone / Hartl, Lena / Bethge, Wolfgang / Matthes-Martin, Susanne / Bader, Peter / Albert, Michael H / Maecker-Kolhoff, Britta / Greil, Johann / Einsele, Hermann / Schlegel, Paul-Gerhardt / Schuster, Friedhelm R / Kremens, Bernhard / Rossig, Claudia / Gruhn, Bernd / Handgretinger, Rupert / Feuchtinger, Tobias

    Blood

    2015  Volume 125, Issue 12, Page(s) 1986–1994

    Abstract: Hematopoietic stem cell transplantation (HSCT) has improved over the last few decades. However, viral infections are often refractory to pharmacologic treatment and require alternative treatment strategies such as immunotherapy. Adenovirus (AdV) is th ... ...

    Abstract Hematopoietic stem cell transplantation (HSCT) has improved over the last few decades. However, viral infections are often refractory to pharmacologic treatment and require alternative treatment strategies such as immunotherapy. Adenovirus (AdV) is th predominant disease-causing pathogen in pediatric HSCT. In a clinical trial, we analyzed safety and efficacy of ex vivo adoptive T-cell transfer (ACT) with hexon-specific T cells, predominantly of the T-helper cell 1 (Th1) phenotype, in 30 patients with AdV disease or viremia. ACT was feasible with no acute toxicities or significant onset of graft-versus-host disease. ACT led to in vivo antiviral immunity for up to 6 months with viral control, resulting in complete clearance of viremia in 86% of patients with antigen-specific T-cell responses. After ACT and a follow-up of 6 months, overall survival was markedly increased in responders (mean, 122 days; 15 survivors) compared with nonresponders who all died shortly after ACT (mean, 24 days; no survivors). AdV-related mortality was 100% in nonresponders compared with 9.5% in responders (≥1 log reduction of DNA copies per milliliter after ACT). In summary, ex vivo ACT of AdV-specific Th1 cells was well tolerated and led to successful and sustained restoration of T-cell immunity correlated with virologic response and protection from virus-related mortality. This cellular immunotherapy is a short-term available and broadly applicable treatment. The study is registered at European Union Clinical Trials Register as 2005-001092-35.
    MeSH term(s) Adenoviridae Infections/complications ; Adenoviridae Infections/etiology ; Adolescent ; Adoptive Transfer ; Adult ; Capsid Proteins/metabolism ; Child ; Child, Preschool ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunotherapy, Adoptive/methods ; Infant ; Male ; Middle Aged ; Phenotype ; Probability ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; Th1 Cells/cytology ; Treatment Outcome ; Young Adult
    Chemical Substances Capsid Proteins ; hexon capsid protein, Adenovirus
    Language English
    Publishing date 2015-01-23
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2014-06-573725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation.

    Feuchtinger, Tobias / Opherk, Kathrin / Bethge, Wolfgang A / Topp, Max S / Schuster, Friedhelm R / Weissinger, Eva M / Mohty, Mohamad / Or, Reuven / Maschan, Michael / Schumm, Michael / Hamprecht, Klaus / Handgretinger, Rupert / Lang, Peter / Einsele, Hermann

    Blood

    2010  Volume 116, Issue 20, Page(s) 4360–4367

    Abstract: Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral immunity after SCT ...

    Abstract Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral immunity after SCT and could protect from CMV-related complications. However, logistics of producing virus-specific T-cell grafts limited the clinical application. We treated 18 patients after allo-SCT from human leukocyte antigen-mismatched/haploidentical or human leukocyte antigen-matched unrelated donors with polyclonal CMV-specific T cells generated by ex vivo stimulation with pp65, followed by isolation of interferon-γ-producing cells. Patients with CMV disease or viremia refractory to antiviral chemotherapy or both were eligible for adoptive T-cell transfer and received a mean of 21 × 10³/kg pp65-specific T cells. In 83% of cases CMV infection was cleared or viral burden was significantly reduced, even in cases of CMV encephalitis (n = 2). Viral control was associated with in vivo expansion of CMV-specific T lymphocytes in 12 of 16 evaluable cases, resulting in reconstitution of antiviral T-cell responses, without graft-versus-host disease induction or acute side effects. Our findings indicate that the infusion of low numbers of CMV-specific T cells is safe, feasible, and effective as a treatment on demand for refractory CMV infection and CMV disease after allo-SCT.
    MeSH term(s) Adolescent ; Adoptive Transfer/methods ; Adult ; Child ; Child, Preschool ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/therapy ; Cytomegalovirus Infections/virology ; Feasibility Studies ; Follow-Up Studies ; Haploidy ; Histocompatibility Testing ; Humans ; Middle Aged ; Phosphoproteins/immunology ; Recurrence ; Stem Cell Transplantation ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation ; Time Factors ; Treatment Outcome ; Viral Matrix Proteins/immunology
    Chemical Substances Phosphoproteins ; Viral Matrix Proteins ; cytomegalovirus matrix protein 65kDa
    Language English
    Publishing date 2010-07-12
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2010-01-262089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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