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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 3 (1997), S. S55 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Multiple immunsuppressive Bedingungen wie neoplastische Grunderkrankungen selbst, immunsuppressive Behandlung mit zytotoxischen Substanzen und Kortikosteroiden, aber auch die schwere und irreversible, erworbene Immunsuppression bei AIDS machen den Menschen signifikant empfänglicher für ein breites Spektrum viraler Infektionen und erhöhen deren Morbidität und Mortalität. Sowohl T- als auch B-Zell-Abnormalitäten und -Defizienzen können für die Erhöhung dieser Suszeptibilität verantwortlich sein. Einige Virusinfektionen führen eher zu schweren Krankheitsverläufen unter einer zellvermittelten Immunsuppression, andere nehmen durch eine beeinträchtigte humorale Immunität des Wirts protrahierte und schwere Verläufe. Virusinfektionen hingegen, denen eine Immunpathogenese zugrunde liegt, d. h. deren zytopathogenen Effektormechanismen vom Immunsystem des Wirts stammen, verlaufen unter einer ausgeprägten Immunsuppression eher klinisch stumm. Unter diesen Bedingungen fehlen allerdings die Mechanismen, die zu einer Eliminierung der Virusinfektion führen. In vielen Fällen kommt es so zur Persistenz des Erregers unter Immunsuppression und zur klinischen Manifestation der Infektion in der Phase der immunologischen Rekonstitution, z. B. einige Wochen nach Absetzen oder Reduktion der immunsuppressiven Therapie. Eine herausragende Bedeutung bezüglich der Morbidität und Mortalität von Virusinfektionen beim immunkompetenten Patienten kommt den Viren der Herpesgruppe zu. Bei hoher Durchseuchungsquote der Bevölkerung und der Eigenschaft der Viren, latent im Organismus zu verbleiben, führen Reaktivierung und Primärinfektionen bei immunsupprimierten Patienten zu lebensbedrohlichen Situationen.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 5 (1999), S. 1066-1074 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Eine Vielzahl von metabolischen Störungen bei Tumorpatienten, zum einen durch die ausgedehnte Erkrankung, zum anderen durch die Tumorbehandlung, sind beschrieben worden [1]. Wenn es sehr rasch zu derartigen metabolischen Veränderungen kommt, insbesondere zu deutlichen Elektrolytverschiebungen, wie Hyperkaliämie, Hyperkalzämie oder Hyponatriämie, so handelt es sich um onkologische Notfälle, die den Tumorpatienten innerhalb kürzester Zeit letal gefährden können. Die frühzeitige Identifikation von Hochrisikopatienten, die Prophylaxe und die zielgerichtete rasche Therapie von metabolischen Störungen ist essentielles Repertoire des internistischen Onkologen.
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  • 3
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Infektionen stellen eine der häufigsten und bedrohlichsten Komplikationen bei Tumorpatienten dar. Dabei sind Inzidienz und Schweregrad der infektiösen Komplikationen weitgehend abhängig von der mit der Grunderkrankung assoziierten Immundefizienz und der Art und Intensität der antineoplastischen Therapie. So treten beispielsweise bei etwa 5–10% der Patienten mit soliden Tumoren tödlich verlaufende Infektionen auf, wohingegen bei Patienten mit akuten Leukämien nach allogener Stammzelltransplantation letale Infektionskomplikationen in bis zu 40% berichtet werden. Bei Patienten mit Tumorerkrankungen treten Infektionen mit einer Vielzahl verschiedener Erreger und mit unterschiedlichen Manifestationen auf. In dem folgenden Kapitel wurden einige dieser infektiösen Komplikationen ausgewählt, die aufgrund der Frequenz oder assoziierten Mortalität als besonders bedeutsam einzustufen sind.
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  • 4
    ISSN: 1433-0563
    Keywords: Key words Testicular cancer • Late toxicity • Chemotherapy • Radiotherapy • Leukemia • Cisplatin • Neurotoxicity • Ototoxicity • Vascular toxicity • Renal toxicity ; Schlüsselwörter Hodentumoren • Spättoxizität • Chemotherapie • Strahlentherapie • Leukämie • Cisplatin • Neurotoxizität • Ototoxizität • Gefäßtoxizität • Nephrotoxizität
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Verbesserung der Überlebensraten bei der Behandlung von Patienten mit Hodentumoren wird von der Sorge um mögliche Langzeitnebenwirkungen der eingesetzten Therapieformen begleitet. Eine sekundäre Neoplasie ist eine gefürchtete Langzeitnebenwirkung, die die ansonsten exzellente Prognose kurativ behandelter Patienten erheblich beeinträchtigt. Patienten mit Hodentumoren haben ein etwa 2fach erhöhtes Risiko, 25–30 Jahre nach Diagnosestellung an einer malignen Zweitneoplasie erkrankt zu sein, das entspricht einer kumulativen Inzidenz von 16–23 %. Das Risiko für sekundäre solide Tumoren ist vorwiegend mit der Strahlentherapie verbunden und scheint mit zunehmender Beobachtungsdauer anzusteigen. Für folgende Tumoren ist ein statistisch signifikant erhöhtes relatives Risiko belegt: Magenkarzinome, Pankreaskarzinome, Blasenkarzinome, kolorektale Karzinome, Prostatakarzinome, Nierenzellkarzinome, Schilddrüsenkarzinome, Melanome, Sarkome und Non-Hodgkin-Lymphome. Nach alleiniger Chemotherapie ist das Risiko für sekundäre solide Tumoren nicht signifikant erhöht. Das Risiko für sekundäre Leukämien ist auch mit der Strahlentherapie aber vorwiegend mit dem Einsatz von Chemotherapie assoziiert. Neuere klinische Analysen der Daten von Patienten mit Hodentumoren haben nach Durchführung einer Chemotherapie ein 10- bis 300faches Risiko für eine Sekundärleukämie gezeigt. Das erhöhte Risiko bezieht sich nur auf die ersten zwei Jahrzehnte nach der Diagnosestellung, danach besteht kein Unterschied zur Normalbevölkerung. Etoposid scheint leukämogen zu sein, insbesondere nach kumulativen Dosen über 2 g/m2. Die genauen Zusammenhänge mit der Dosis, der Applikationsweise, den anderen Zytostatika und der Radiotherapie sind allerdings noch nicht vollständig geklärt. Auf dem Boden der derzeit verfügbaren Daten von Patienten mit Hodentumoren ist festzustellen, daß nach einer chemotherapeutischen Behandlung ein signifikant erhöhtes Risiko für eine Sekundärleukämie besteht. Bei gleichzeitiger Abwägung der hohen Heilungsrate ist das Risiko für den individuellen Patienten gering, aber nicht vollständig zu vernachlässigen. Das sekundäre Raynaud-Syndrom stellt die wesentliche vaskuläre Spättoxizität dar und betrifft etwa ein Drittel der Patienten nach kurativer Chemotherapie des Hodentumors. Bei einem fünftel der Patienten tritt eine arterielle Hypertonie auf. Es ist allerdings zu erwarten, daß die Häufigkeit dieser Nebenwirkungen durch Einsatz des PEB-Regimes (im Vergleich zum PVB-Regime) in Zukunft sinken werden. Schwere vaskuläre Komplikationen scheinen nur sehr selten aufzutreten. Weitere häufige Toxizitäten sind Ototoxizität und periphere Neuropathie. Einer der wichtigsten Risikofaktoren für das Auftreten dieser Toxizitäten ist die kumulativ applizierte Cisplatindosis. Bei mehr als der Hälfte der jungen Patientenpopulation ließen sich, nach erfolgreicher cisplatin-basierten Kombinationschemotherapie, persistierende Veränderungen der Gonadotropinspiegel und eine Leydigzellinsuffizienz nachweisen. Etwa ein viertel der Patienten wiesen erniedrigte Magnesium- oder Phosphatwerte auf, oder hatten einen erhöhten Kreatininwert im Serum. Diese Toxizitäten führen selten zu klinischen Symptomen. Zusammengefaßt läßt sich derzeit feststellen, daß 3-4 Serien einer Therapie mit Bleomycin, Cisplatin und Etoposid bei Patienten mit Hodentumoren nur selten zu symptomatischen Störungen der Organfunktionen und zu einer Beeinträchtigung der Lebensqualität führen. Die vorliegende Übersicht zeigt, daß das „Modell Hodentumor“ nicht nur die Therapieentwicklung, bei der es ja entscheidend zur Definition der Rolle von Cisplatin, Etoposid und in neuerer Zeit von Ifosfamid in der klinischen Onkologie beigetragen hat, sondern auch für die Untersuchung der Langzeitfolgen dieser eingesetzten Therapien von breiter klinischer Relevanz ist. Somit könnte der maligne Hodentumor nicht nur „a model for a curable neoplasm“ (LH. Einhorn) sondern auch „a model for the study of late sequelae of modern oncological therapies“ darstellen.
    Notes: Summary Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25–30 years after the diagnosis, resulting in a cumulative incidence of 16–23 % at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3–4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a “model for a curable neoplasm” (L. H. Einhorn) but can also be seen as a “model for the study of late sequelae of modern oncological therapies”.
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  • 5
    ISSN: 1432-0584
    Keywords: Megakaryopoiesis ; Antiplatelet-antibodies ; PAP-slide technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pure megakaryocytic colonies, megakaryocytic-erythroid colonies and mixed hemopoietic colonies can be cultured from human bone marrow under appropriate culture conditions. Human plasma and mercaptoethanol support the growth for these different types of hemopoietic colonies. However, the addition of medium conditioned by leucocytes in the presence of phytohemagglutinin (PHA-LCM), as a source of thrombopoietin, is required for the formation of megakaryocytic colonies or megakaryocytes within mixed colonies. Megakaryocytes were identified by their typical morphological appearance in culture. Pure megakaryocytic colonies, megakaryocytic-erythroid colonies and mixed colonies were plucked by micropipette and analysed by the PAP-slide technique using antibodies to human factor VIII-related protein or serum derived from a patient with posttransfusion purpura; this particular serum demonstrated anti-PlA1 antibody activity. These antibodies might provide an excellent probe to identify megakaryocytic progeny from committed and non-committed hemopoietic progenitors, facilitating studies of early events in megakaryopoiesis.
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  • 6
    ISSN: 1432-0584
    Keywords: Stem cells ; Hodgkin's disease ; T-cell population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pluripotent stem cells (CFU-GEMM) give rise to multilineage hemopoietic colonies in culture. The cellular composition revealed that mixed colonies contain cells of different myeloid lineages and mononuclear cells with T-cell surface antigens. T-lymphocytes of primary colonies, replated secondary and tertiary colonies from a patient with Hodgkin's Lymphoma were identified by their reaction with the monoclonal antibody OKT 8. Evidence for a common progenitor of myeloid and lymphoid cells is provided by analysis of individual secondary and tertiary colonies using OKT 3, OKT 4, OKT 8, VIM-D 5, and Ig M + D antibodies for each individual colony. Primary mixed, replated secondary and tertiary colonies revealed OKT 8 positive cells. No reaction with OKT 3, OKT 4, VIM-D 5, OR Ig M+D was observed.
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  • 7
    ISSN: 1432-0584
    Keywords: Key words Bone marrow transplantation ; Magnetic resonance imaging ; Magnetic resonance spectroscopy ; Therapy monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Lumbar bone marrow was assessed by means of magnetic resonance (MR) in 23 examinations of eight patients who underwent autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT). Various imaging and spectroscopic techniques were applied for measurements carried out prior to conditioning for ABMT/PBSCT and in the course of reconstitution and correlated with clinical and blood chemistry data in these patients. The signal intensity from lumbar bone marrow was determined in T1-weighted and water- and fat-selective MR images. The distribution of the magnetic field was demonstrated by a field-mapping method. Localized proton spectroscopy was performed from volume elements of 2 ml located in the central region of vertebral bodies in order to evaluate the fraction of the water signals, the transverse relaxation times T2 of the signals from water and lipids, and the line widths of the spectral signals. Regions of bone marrow after inflammatory conditions or intensive irradiation are shown to be not involved in marrow reconstitution. Additional information about marrow composition was obtained by the magnetic field mapping and by the line widths in the spectra. Considerable alterations of the amount of paramagnetic hemosiderin were revealed following transplantation. Patients with low water signal and strong local inhomogeneities of the magnetic field in the marrow prior to transplantation had a delayed hematopoietic reconstitution compared with the patients lacking these MR features.
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  • 8
    ISSN: 1279-8509
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40–50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin ± ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (GCSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.
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  • 10
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an active broad-spectrum antitumor agent, including its use in urological malignancies, particularly urothelial tract cancer and testicular cancer. The mechanism of action, based on the premature stabilization of the microtubule assembly with disruption of the cytoskeletal framework, is completely different from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer, with an overall response rate of 40–50% being obtained in previously untreated patients. These promising single-agent results have prompted the use of combination regimens including, in particular, cisplatin and paclitaxel. A high degree of activity for the cisplatin-paclitaxel combination as reflected by responses in 50–80% of patients, including a substantial number of complete responses (〉30%), has been identified. The role of other agents such as vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two-drug combination currently remains open. The combination of paclitaxel plus ifosfamide or vinorelbine in the absence of a platinum derivative has yielded rather disappointing results. Of particular interest may be the combination of paclitaxel and carboplatin. Both drugs can be given to patients with impaired renal function. Overall response rates of 45–60% have been reported in phase II studies. The so-called platelet-sparing effect of paclitaxel given in combination with carboplatin has resulted in a surprisingly low frequency of myelotoxicity, particularly thrombocytopenia. The combination of paclitaxel with carboplatin is being compared in an ongoing trial against the current standard MVAC regimen (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic disease. Furthermore, the activity of paclitaxel-based combinations is currently being explored in the neoadjuvant setting in phase II studies, and the potential for the combination with the other new promising agent – gemcitabine – will be evalutated in a phase I setting. In prostate cancer, estramustine phosphate is widely used as palliative treatment for patients with hormone-refractory disease. In vitro synergistic activity has been observed between estramustine and paclitaxel in prostate-cancer cell lines, although paclitaxel has not demonstrated single-agent activity in patients with hormone-refractory prostate cancer. In clinical trials the combination of the two agents was associated with increased gastrointestinal toxicity. The addition of etoposide as a third drug has yielded prostate-specific antigen (PSA)-response rates of 〉50%, but data on quality of life and survival time have not been reported for these combinations. A true clinical role for paclitaxel in prostate cancer has therefore not been established. Paclitaxel has finally demonstrated single-agent activity in relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials, indicating different mechanisms of resistance to cisplatin and paclitaxel. These results have formed the rationale for the introduction of paclitaxel as part of combination chemotherapy regimens in patients with relapsed but chemosensitive testicular cancer. Preliminary results demonstrate that paclitaxel can be safely included into these conventional-dose combination regimens. When it is used prior to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but it appears that paclitaxel-based combinations can achieve a substantial response rate in patients with relapsed disease.
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