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  • 1
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Acute leukaemia ; Knochenmarktransplantation ; akute Leukämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation München wurden von August 1975 bis Juni 1980 insgesamt 17 Patienten mit rezidivierter, akuter Leukämie mit Knochenmark von HLA-identischen Geschwistern transplantiert. Die antileukämische und immunsuppressive Vorbehandlung bestand aus BCNU, Cytosin-Arabinosid, Cyclophosphamid in hoher Dosierung und Ganzkörperbestrahlung mit etwa 9 Gy Körpermitteldosis an einer60Co-Doppelbestrahlungsanlage. Die Prophylaxe einer Graft-versus-Host Krankheit (GvHK) wurde in allen Fällen mit Methotrexat durchgeführt, bei neun Patienten wurde als zusätzliche GvHK-Prophylaxe das Knochenmark mit Anti-T-Zell-Globulin inkubiert, von dem die Antikörper gegen hämopoetische Stammzellen absorbiert waren. Zwei von fünf auswertbaren Patienten, die unbehandeltes Knochenmark erhalten hatten, entwickelten chronische GvHK, während kein Patient nach ATCG-Inkubation des Knochenmarkes eindeutige GvH-Krankheit bekam. Sechs Patienten leben in Vollremission zwischen einem und 33 Monaten nach Knochenmarktransplantation (KMT). Fünf Patienten starben mit Rezidiven zwischen 3 1/2 und 24 Monaten nach KMT, drei Patienten mit interstitieller Pneumonie innerhalb von 3 Monaten nach KMT und drei Patienten innerhalb von 4 Wochen ohne ausreichende Knochenmarkfunktion. Vier von 13 Patienten, die vor mehr als 6 Monaten transplantiert wurden, überleben zur Zeit 11, 14, 19 und 33 Monate in Vollremission. Unsere Ergebnisse bestätigen, daß selbst in fortgeschrittenen Stadien akuter Leukämie durch KMT noch langfristige Remissionen erreichbar sind.
    Notes: Summary Seventeen patients with relapsed, acute leukemia were grafted with bone marrow from HLA-identical siblings by the ‘Munich Cooperative Group for Bone Marrow Transplantation’ during the period from August 1975 to June 1980. The antileukemic and immunosuppressive conditioning treatment consisted of high doses of Bischlorethyl nitrosourea, Cytosine-Arabinoside and Cyclophosphamide, as well as, total body irradiation of about 9 Gy (midline body dose) from dual60Cobalt sources. Methotrexate was given to all patients for prophylaxis of graft-versus-host disease (GvHD). Nine patients received marrow that was treated with anti-T-cell globulin (ATCG) “in vitro”. — Crossreacting antibodies against hemopoietic stem cells were removed by absorption. Two of 5 evaluable patients given untreated marrow developed chronic GvHD, while patients given ATCG-treated marrow did not show unequivocal symptoms of GvHD. Six patients are in complete remission one to 33 months following bone marrow transplantation (b.m.t.) Five patients died with relapses of leukemia between 3 1/2 and 24 months following b.m.t., 3 patients died with interstitial pneumonia within 3 months of b.m.t. and 3 patients died with insufficient graft function within 4 weeks of b.m.t. Four of thirteen patients that were grafted more than 6 months ago are presently alive and in continuous complete remission at 11, 14, 29 and 33 months following b.m.t. Our results confirm that longterm remissions can be obtained with b.m.t. in patients with acute leukemia in advanced stage.
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  • 2
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Aplastic anaemia ; Knochenmarktransplantation ; Aplastische Anämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation — München (AG-KMT) wurden vom März 1975 bis Mai 1980 insgesamt 12 Patienten wegen schwerer, aplastischer Anämie mit Knochenmarktransplantation (KMT) behandelt. Sechs Patienten überleben derzeit mit normalem Blutbild und Knochenmark zwischen 10 Monaten und mehr als 5 Jahren nach KMT von HLA-identischen Geschwistern, eine Patientin steht noch in ambulanter Behandlung wegen lokalisierter, chronischer Graft-versus-Host Krankheit (GvHK), fünf Patienten sind klinisch gesund. Sechs Patienten starben, ein Patient starb am Tag vor KMT mit Hirnblutung, drei Patienten 32, 40 und 55 Tage nach KMT an den Folgen der Transplantatabstoßung, einer an schwerer GvHK 85 Tage nach KMT und einer 87 Tage nach KMT vermutlich an interstitieller Pneumonie nach Hirnblutung. Drei von 6 Patienten, die nur mit Cyclophosphamid (CY) vorbehandelt waren, starben infolge Abstoßung des Transplantates. Zwei erwachsene Patienten, die mit CY und „total lymphoid irradiation“ vorbehandelt waren, und drei Kinder, die nach KMT unbestrahlte Leukocytenkonzentrate von Knochenmarkspender erhalten hatten, stießen das Transplantat nicht ab. Die Ergebnisse der AG-KMT sind vergleichbar denen großer, spezialisierter Zentren für KMT und zeigen die Möglichkeiten einer Heilung schwerer aplastischer Anämien durch KMT von HLA-identischen Geschwistern. Die Erfolge sind besser bei frühzeitiger KMT.
    Notes: Summary From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and “total lymphoid irradiation” and three children, who were given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Osteogenic sarcoma ; Methotrexate ; Radioimmunoassay ; Osteosarkom ; Methotrexat ; Radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 22 Patienten mit osteogenem Sarkom, die 103 hochdosierte Methotrexatinfusionen (6–8,5 g/m2 in 4–6 h) erhielten, wurde mit einem eigenen spezifischen und rasch durchführbaren Radioimmunoassay die Plasmapharmakokinetik des Methotrexats untersucht. Bei nichttoxischen Verläufen lag die Plasmakonzentration nach 24 h unter 8,0 × 10−6 mol/l, nach 48 h unter 8,0 × 10−7 mol/l und nach 72 h unter 4,25 × 10−7 mol/l. Alle Patienten mit 48 h-Werten über 1 × 10−6 mol/l entwickelten schwere toxische Erscheinungen in Form von Knochenmarksdepression und Stomatitis, die durch eine verzögerte Ausscheidung des Methotrexats bedingt war. Der Anstieg des Serumkreatinins war kein zuverlässiges Kriterium für toxische Verläufe. Die Bestimmung der 48- und 72h-Methotrexat-Plasmakonzentrationen erwies sich als zuverlässiger Parameter zur Erfassung von Patienten mit drohender Toxizität. Sie ermöglicht somit, rechtzeitige therapeutische Maßnahmen, z.B. in Form einer zusätzlichen Leukovorintherapie zu ergreifen.
    Notes: Summary In 22 patients with osteogenic sarcoma, treated with 103 high-dose methotrexate infusions (6–8.5 g/m2 in 4–6 h) plasma methotrexate levels were measured with a specific and rapid radioimmunoassay. Nontoxic infusions were associated with methotrexate concentrations below 8.0 × 10−6 mol/l at 24 h, 8.0 × 10−7 mol/l at 48 h and 4.25 × 10−7 mol/l at 72 h. All patients with 48 h methotrexate levels above 1 × 10−6 mol/l manifested severe toxicity with myelosuppression and stomatitis due to delayed methotrexate excretion. Rise of serum creatinine was not reliable to predict oxicity. Determination of 48-and 72-h methotrexate concentrations proved to be a valuable method for identifying patients at high risk for toxic side effects. Additional citrovorum factor may thus be given in time.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Wolman's disease ; Storage ; Cholesterylester ; Triglycerides ; Acid lipase ; Adrenal calcification ; Dyserythropoietic changes ; Foam cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of Wolman's disease is described in a German infant who died at the age of 4 months. Hepatosplenomegaly, abdominal distention, gastrointestinal symptoms, dyserythropoietic changes in the bone marrow, but not adrenal calcification on X-ray were present. Stored lipid material could be demonstrated in liver, spleen, intestine, adrenals, thymus, kidneys, blood cells, but not in the central nervous system. Cholesterylesters and triglycerides were markedly increased in liver and spleen. Lysosomal acid lipase was found to be decreased in leucocytes and liver to less than 10% of normal, when measured with synthetic and natural substrates.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 137 (1981), S. 285-290 
    ISSN: 1432-1076
    Keywords: Thalassemia ; Hemosiderosis ; Desferrioxamine ; Liver storage iron ; Ferritin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten children with transfusion dependent anemias (thalassemia, sideroblastic anemia, congenital pure red cell aplasia) received either intravenous desferrioxamine (DF) in increasing doses up to 450 mg/kg at the time of transfusion or daily subcutaneous DF up to 110 mg/kg on an outpatient basis. No patient on intravenous DF reached a negative iron balance. All children with a subcutaneous DF dose of more than 60 mg/kg obtained a negative iron balance with a net iron excretion (transfusion iron already substracted) between 206 to 810 mg (mean 496 mg) monthly. The effectiveness of regular subcutaneous DF on liver storage iron could be confirmed in 4 patients by liver biopsy, showing a decrease between 40–60% iron after 12–14 months of chelation therapy. So far the daily iron excretion has remained constant with a given dose of DF over a period up to 15 months. Even if poor compliance in some patients is taken into account, it is possible with this method of treatment to prevent further accumulation of iron in chronically transfused children.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 140 (1983), S. 221-230 
    ISSN: 1432-1076
    Keywords: Familial hemophagocytic lymphohistiocytosis ; Farquhar's disease ; Histiocytosis ; Retichlosis ; Immune deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Familial hemophagocytic lymphohistiocytosis (FHL) is probably a genetically transmitted disease affecting infants and very young children. Cardinal symptoms are fever, hepatosplenomegaly, and pancytopenia. Frequently meningeal involvement is seen, manifested by neurologic symptoms and a lymphohistocytic pleocytosis with increased protein levels in the cerebrospinal fluid. Characteristic laboratory findings in FHL are hypertriglyceridemia and hypofibrinogenemia, which are reversible with treatment. The disease has been rapidly fatal in most patients, but recently longterm remissions have been achieved with cytotoxic agents. Pathohistologic examination shows a widespread infiltrate of lymphocytes and mature macrophages with prominent hemophagocytosis affecting especially liver, spleen, lymph nodes and the central nervous system. Atrophy of the lymphatic tissue is a common finding. From the histologic picture FHL has to be grouped among the histiocytoses of reactive origin since the cells involved show no signs of malignancy. The etiology and pathogenesis of FHL are not known at present. Immunologic studies present evidence for a disturbed function of T lymphocytes, but a secondary immune defect seems to be more likely than primary immune deficiency. Among the broad clinical spectrum of histiocytic disorders especially histiocytic reactions due to infection, histiocytosis X and malignant histiocytosis have to be considered in the differential diagnosis of FHL.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 37 (1978), S. 89-94 
    ISSN: 1432-0584
    Keywords: Akute lymphoblastische Leukämie ; Prognostische Faktoren bei ALL ; Messung der Zellgröße ; Acute lymphoblastic leukemia ; Prognostic factors in ALL ; Cell size measurement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The significance of cell size as a prognostic indicator in acute lymphoblastic leukemia (ALL) is controversial. Accuracy in measurement of cell size can be improved by determination of cell areas instead of single cell diameters. In the present study cell areas of 200 cells were determined in pretreatment bone marrows of 35 children with ALL. For better comparison with other studies which had used cell diameters only, the measured area was expressed as circle area from which the circle diameter was calculated. Cells with a diameter of 〉 12μm were defined as macrolymphoblasts (MLB). Several clinical characteristics considered to be risk factors in ALL were ascertained for each patient. The duration of first complete remission was used to assess the prognostic significance of cell size and of number of risk factors. In contrast to previous reports patients with more than 25% MLB had longer remissions. However, nearly all patients of this group had no or one risk factor only. When patients with more than one risk factor were excluded from statistical analysis, the group with more than 25 % MLB had no longer a better prognosis compared to the group with 25% MLB or less. Thus, in this study the percentage of MLB was not an independent prognostic indicator for risk of relapse in ALL.
    Notes: Zusammenfassung Die Bedeutung der Zellgröße als prognostischer Faktor bei Patienten mit akuter lymphoblastischer Leukämie (ALL) ist umstritten. Die Messung der Zellfläche anstelle des Zelldurchmessers ergibt genauere Werte. In der vorliegenden Studie wurde bei 35 Kindern mit ALL die Zellfläche von 200 Zellen in den Knochenmarksausstrichen vor Therapiebeginn bestimmt. Aus Vergleichsgründen mit anderen Arbeiten, die lediglich Zelldurchmesser benützt hatten, wurde die gemessene Fläche einer Kreisfläche gleichgesetzt und der Kreisdurchmesser bestimmt. Zellen mit einem Durchmesser von 〉 12μm wurden als Makrolymphoblasten (MLB) bezeichnet. Für jeden Patienten wurden die klinischen Merkmale, die als Risikofaktoren bei der ALL gelten, ermittelt. Die Dauer der ersten Remission diente als Maßstab für die Prognose. Im Gegensatz zu vorhergehenden Berichten hatten Patienten mit mehr als 25% MLB eine bessere Prognose, was Frührezidive anbelangte. Fast alle Patienten dieser Gruppe hatten jedoch keinen oder nur einen Risikofaktor. Wenn bei der statistischen Analyse nur Patienten mit keinem oder einem Risikofaktor berücksichtigt wurden, zeigte die Gruppe mit mehr als 25% MLB keine bessere Prognose mehr gegenüber der Gruppe mit 25 % MLB und weniger. In der vorliegenden Studie war der Anteil der Makrolymphoblasten kein unabhängiger prognostischer Parameter für das Rezidivrisiko bei ALL.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: Knochenmarktransplantation ; Vermeidung von GvH ; T-Zell-Globulin ; Bone marrow transplantation ; Prevention of GvH ; Preincubation of donor bone marrow ; Specific anti-T-cell globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.
    Notes: Zusammenfassung Tierexperimentelle Befunde ergaben den Hinweis, daß bei Knochenmarktransplantation mit inkompatiblem Spendermark eine Vorinkubation des Spendermarkes mit xenogenem Anti-T-Zell-Globulin eine sonst toxisch verlaufende Graft versus Host-(GvH)Erkrankung vermeidet. Bei drei Patienten mit akuter lymphatischer Leukämie wurde dieses Prinzip bei der Knochenmarktransplantation erfolgreich klinisch angewandt. Zur Anwendung gelangte ein spezifisches antihumanes Anti-T-Zell-Globulin (ATCG-H), das durch mehrere Absorptionsschritte aus rohem antihumanem Globulin (ATG) gewonnen wurde. Eine Vortestung des Serums ergab eine unveränderte Reaktion gegen menschliche T-Zell-Lymphozyten ohne toxische Nebenwirkungen auf in vitro nachweisbare Vorläuferzellen der Hämopoese (CFU-C). Die Knochenmarktransplantation wurde bei allen drei Patienten nach üblicher Chemotherapie („Konditionierung“) und Ganzkörperbestrahlung mittels vorinkubiertem Spendermark von HLA-identischen Geschwisterndurchgeführt. Toxische Nebenwirkungen durch die Vorinkubation traten nicht auf. Anzeichen einer GvH wurden bisher (24, 7, 6 Monate) bei den Empfängern nicht beobachtet. Die in vitro -Vorinkubation von Spenderknochenmark kann somit als ungefährlicher neuer Versuch zur Vermeidung einer GvH beim Menschen empfohlen werden.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 42 (1981), S. 325-327 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    ISSN: 1432-0584
    Keywords: Acute leukemia ; Bone marrow transplantation ; Anti-T-cell-globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Anti-human-thymocyte globulin (AHTZG) was applied to prevent GvHD in clinical bone marrow transplantation. AHTZG produced by absorption with several cell preparations reacted specifically with T-lymphocyte populations and was no longer inhibitory to human CFUc and bone marrow growth in diffusion chambers. Marrow grafts of 14 patients with ALL were incubated in vitro with AHTZG and transferred to the recipients conditioned with antileukemic chemotherapy and total body irradiation of 1000 rad. Ten patients were transplanted after relaps, four patients during remission. The patients tolerated the marrow without side effects and a hemopoietic engraftment was seen in 12 cases. Three patients showed signs of GvHD on the skin, two of them showed later on also manifestations in the liver. In the other cases no GvHD could be detected. Five out of 14 patients are still alive between 144 and 964 days post transplantation in remission.
    Type of Medium: Electronic Resource
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