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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 288-290 
    ISSN: 1432-1335
    Keywords: Keywords Pharmacoeconomics ; High-dose chemotherapy ; Peripheral blood stem cell support
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Discussion of the total costs and cost-effectiveness ratios of patients receiving high-dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) is controversial. In Germany, no reliable data are available, whereas in other countries this issue has been extensively studied. We performed a pharmacoeconomic evaluation on all patients (n = 37) treated with HDC and PBSCS at our institution between July 1994 and June 1997. Patients suffered from high-risk or poor-prognosis breast cancer (n = 24), Hodgkin's disease (n = 3), high-grade non-Hodgkin's lymphoma (n = 4), multiple myeloma (n = 2), small-cell cervical cancer (n = 1), malignant hystiocytosis (n = 1) and testicular cancer (n = 2). For pharmacoeconomic evaluation, the period from initiation of induction chemotherapy (IC) until reconstitution after the last course of HDC and PBSCS was considered. A total of 18 patients received IC/HDC/PBSCS for locally advanced or systemic disease, and 19 patients received adjuvant or consolidation IC/HDC/PBSCS. Treatment protocols were heterogeneous. Patients were treated with two to five courses (median two) respectively of IC and sequential mono-HDC (n = 26), tandem-HDC (n = 10) or triple-HDC (n = 1). All patients received granulocyte/macrophage-colony-stimulating factor (G-CSF) for stem cell mobilisation and for amelioration of neutropenia after HDC. The relative costs (based on supplier prices) for the total amount of drugs prescribed during the in-patient period was 29.8% for G-CSF, 35.8% for blood products 18.5% for chemotherapy, 2.4% for antiemetics, 5.9% for antimicrobial drugs and 7.6% for other drugs. Contrary to expectations, antimicrobial drugs had only a minor pharmacoeconomic impact during IC/HDC/PBSCS in patients with high-risk or poor-prognosis malignancies, indicating that prolonged septic complications were uncommon in our institution. We conclude that pharmacoeconomic evaluations in IC/HDC/PBSCS might be integrated into the effort to ensure quality control and monitoring.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Urologe 37 (1998), S. 621-624 
    ISSN: 1433-0563
    Keywords: Key words Markerpositive germ cell tumors • Residual tumor resection • Salvage chemotherapy • High dose chemotherapy ; Schlüsselwörter Markerpositive Keimzelltumoren • Residualtumorresektion (RTR) • Salvagechemotherapie • Hochdosischemotherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Aus einer Gruppe von Patienten mit metastasierten Keimzelltumoren, die sich zwischen 1991 und 1997 einer Residualtumorresektion (RTR) unterziehen mußte, wurden 33 ausgewertet, die zum Operationszeitpunkt markerpositiv waren. Die Ergebnisse der histopathologischen Untersuchung des Residuums, der Verlauf der Tumormarker und das progreßfreie sowie rezidivfreie Überleben wurden beurteilt. Die Krankheitsstadien waren bei Primärdiagnose unterschiedlich: „minimal disease“n = 1, „moderate disease“n = 15 und „advanced disease“n = 17. Diese Patientengruppe hatte durchschnittlich 8,5 cisplatinhaltige Zyklen einer Polychemotherapie erhalten. Nur 11 Patienten wurden nach First-line-Chemotherapie operiert, die übrigen 22 nach Second-line- bzw. Third-line-Chemotherapie. Bei 12 von 31 auswertbaren Patienten konnte eine anhaltende komplette Remission erzielt werden. Die mediane Nachbeobachtungszeit beträgt für diese Gruppe 30 Monate (2–58 Monate). Die Histologie des Resektats und die Höhe der Tumormarker vor der RTR erlauben keine prognostische Einschätzung. Die Operation führt bei 44 % der AFP- und 30 % der HCG-positiven Patienten zu einer anhaltenden Remission. Sind zum Zeitpunkt der RTR die Tumormarker im Normbereich, beträgt die tumorfreie Überlebensrate 72 %; bei präoperativ erhöhten Markern überleben 39 %. Gelingt keine Markernormalisierung durch intensivierte Chemotherapie, so bleibt die RTR die einzige Möglichkeit, um den schicksalhaften Krankheitsverlauf zu beeinflussen.
    Notes: Summary We analyzed 33 patients with disseminated germ cell tumors (GCT) who underwent residual tumor resection (RTR) during the period from 1991–1997. The patients were markerpositive prior to surgery were analyzed. The histopathological examination of the resected masses, the marker dynamics and the relapse-free respectively the progressionfree survival, were evaluated. The status differed at primary diagnosis: minimal disease n = 1, moderate disease n = 15, advanced disease n = 17. The patients received at average 8,5 cisplatin-containing cycles of polychemotherapy. Only 11 patients underwent surgery after first-line-chemotherapy. The remaining received second- or third-line-chemotherapy prior to surgery. In 12 of 31 evaluable patients, a durable CR was achieved. The median follow-up for this group is 30 months (2–58 months). The histopathologic examination of the resected specimen and the tumor marker level prior to RTR do not permit determination of prognostic outcome. After operation 44 % of the AFP-positive and 30 % of the β -HCG-positive patients had a durable remission. If tumor marker levels at time of RTR are within normal range, disease-free survival is 72 %; in case of elevated markers 39 % will survive. If intensive chemotherapy fails to normalize markers, RTR remains the only option to change the fatal course of the disease.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Der Orthopäde 27 (1998), S. 301-304 
    ISSN: 1433-0431
    Keywords: Key words Sample size • Alpha-beta-power • Effect size ; Schlüsselwörter Stichprobenumfang •α-, β-Fehler/Power • Effektgröße
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Aussagekraft einer klinischen Studie hängt in hohem Maße von der Größe der untersuchten Stichprobe ab. Der optimale Stichprobenumfang kann problemlos berechnet werden, wenn α-Fehler, Power und Effektgröße bekannt sind. In Therapiestudien betragen das α-Fehler-Niveau und die Power meist 5% bzw. 90%. Für den Stichprobenumfang ist deshalb die Effektgröße, die vom Kliniker aufgrund medizinischer Überlegungen festgelegt wird, entscheidend. Die möglichen Konsequenzen sowohl zu kleiner als auch zu großer Stichproben werden anhand der inhaltlichen Bedeutung von α-Fehler, Power und Effektgröße erörtert. Zu kleine Stichproben besitzen ein hohes Risiko falsch negativer Ergebnisse und können dazu führen, daß eine möglicherweise wirksame Therapie nicht angewandt wird. Zu große Stichproben können statistisch signifikante Unterschiede zur Folge haben, die klinisch jedoch bedeutungslos sind.
    Notes: Summary A determinant for the evidence of a clinical trial is the magnitude of the sample size. The proper sample size can be easily computed with the knowledge of α, power and effect size. Standard values for α and power in clinical trials are 5% and 90%, respectively. As consequence, effect size is crucial for the sample size. The effect size has to be determined by the clinician according to medical considerations. Possible consequences of sample sizes that are either too small or too large are discussed with regard to the meaning of α, power and effect size. Trials with improper small samples sizes have a high risk of false negative results, and may subsequently prevent the application of a possibly effective therapy. Trials with improper large sample sizes may result in statistically significant differences without any clinical relevance.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' journal of analytical chemistry 361 (1998), S. 377-380 
    ISSN: 1432-1130
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Based on pronounced enhancing effects in combination with other DNA-damaging agents the potentials of Ni(II), Cd(II) and As(III) to interfere with DNA repair processes in HeLa cells was investigated. With respect to oxidative DNA damage, Ni(II) and Cd(II) induced DNA strand breaks starting at concentrations of 250 μM and 5 μM, respectively. The induction of oxidative DNA base modifications like 8-hydroxyguanine was restricted to the cytotoxic concentration of 750 μM Ni(II) and not observed after treatment with Cd(II). In contrast, the removal of oxidative DNA base modifications was inhibited at concentrations as low as 50 μM Ni(II) and 0.5 μM Cd(II). Regarding nucleotide excision repair, Ni(II) and Cd(II) disturbed the DNA-protein interactions involved in the damage recognition step when applying HeLa nuclear protein extracts and a UV-damaged oligonucleotide, while As(III) inhibited the actual incision event. In the case of Ni(II) and Cd(II), this effect was reversible by the addition of Mg(II) and Zn(II), respectively. Furthermore, Cd(II) inactivated the isolated bacterial Fpg protein, most likely by the displacement of Zn(II) from its zinc finger structure. Since DNA is continuously damaged by exogenous and endogenous sources, an impaired repair capacity might well account for the carcinogenic action of the metal compounds.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Magnetresonanztomographie ; Kontrastmittel ; Eisenoxid ; MION ; Glioblastom ; Key words Magnetic resonance imaging ; Contrast medium ; Iron oxide ; MION ; Glioblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: To investigate whether the margins of microscopic tumors can be delineated better with monocrystalline iron oxide nanoparticles (MION), a superparamagnetic contrast medium, than with Gd-DTPA by magnetic resonance imaging (MRI). Methods: MRI and histological examinations were conducted in 28 Wistar rats with sterotactically implanted gliomas (C6 gliomas). Of the 28 animals, 14 were examined after intravenous administration of MION [nine animals received 179 mmol Fe/kg body weight (dose 1), and five, 893 mmol Fe/kg (dose 2)]. The other 14 animals were examined first after i.v. administration of Gd-DTPA (0.2 mmol/ kg) and then after i.v. administration of MION. The extent of the tumors as seen on MRI and at histological study were compared. Results: Iron particles were identified microscopically in tumor cells and in the tumoral interstitium. After administration of MION at dose 1, the contrast-enhanced area of tumor was 1.55-fold greater than the extent of tumor identified by histological study, at dose 2, 2.15-fold. Compared with Gd-DTPA the area of contrast enhancement was greater by a factor of 1.38 with MION administration at dose 1 and by a factor of 1.91 at dose 2. Conclusion: MION provides intra- and extracellular contrast enhancement. The area of the contrast-enhanced tumor is dose-dependently greater with MION than with Gd-DTPA and also greater than the extent of tumor seen at histological study.
    Notes: Zusammenfassung Fragestellung: Verbessert ein superparamagnetisches Kontrastmittel (monocrystalline iron oxide nanoparticle, MION) die MR-tomographische Abgrenzbarkeit mikroskopischer Tumorgrenzen im Vergleich zu Gd-DTPA? Methodik: 28 Wistar-Ratten mit stereotaktisch implantiertem Gliom (C6-Gliom) wurden MR-tomographisch und mikroskopisch untersucht. 14 Tiere hiervon wurden nach intravenöser (i.v.) Gabe der MION untersucht [9 Tiere erhielten 179 μmol Fe/kg Körpergewicht (=Dosierung 1), 5 Tiere 893 μmol Fe/kg (=Dosierung 2)]. 14 Tiere wurden zuerst nach i.v. Gabe von Gd-DTPA (0,2 mmol/kg) und anschließend nach i.v. Gabe der MION untersucht. MR-tomographische und mikroskopische Tumorausdehnungen wurden verglichen. Ergebnisse: Eisenpartikel konnten mikroskopisch in Tumorzellen und im Tumorinterstitium nachgewiesen werden. Nach Gabe der MION in Dosierung 1 war die Ausdehnung des KM-anreichernden Areals in der MRT im Durchschnitt 1,55fach größer als der in der Histologie erkennbare Tumor, bei Dosierung 2 sogar 2,15fach. Im Vergleich mit Gd-DTPA war die KM-anreichernde Fläche nach Gabe der MION in Dosierung 1 um den Faktor 1,38 größer, in Dosierung 2 um den Faktor 1,91. Schlußfolgerungen: MION führen zu einer intra- und extrazellulären KM-Anreicherung. Die Ausdehnung des KM-anreichernden Areals ist dosisabhängig ausgedehnter als die KM-Anreicherung nach Gd-DTPA Gabe und auch ausgedehnter als die morphologisch nachweisbaren Tumorgrenzen.
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  • 6
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Maligne Gliome ; Hirnödem ; Rezidiv ; Magnetresonanztomographie ; Key words Malignant glioma ; Brain edema ; Tumor recurrence ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Purpose: To assess the influence of initial preoperative brain edema in malignant gliomas on regrowth patterns. Subjects and methods: 79 patients with histologically verified supratentorial malignant glioma were prospectively studied by magnetic resonance imaging (MRI) before and every 2–3 months after surgery. The median follow-up time was 11 months. We correlated the configuration of the initial vasogenic edema on T2-weighted images with tumor regrowth patterns on contrast-enhanced T1-weighted images. Results: 35/47 tumor regrowths (75%) imitated the initial edema configuration, while 11/47 occurred within the initial tumor bed; in one case tumor recurrence was multilocal. Conclusion: In glioblastoma, tumor regrowth patterns correlate positively with the configuration of the initial vasogenic brain edema. The initial, „presurgical” peritumoral edema should thus be considered when planning further treatment.
    Notes: Zusammenfassung Fragestellung: Beeinflussen Form und Größe des präoperativen peritumoralen Hirnödems die Rezidiventwicklung bei malignen supratentoriellen Gliomen? Methodik: Prospektiv wurden 79 Patienten mit einem malignen supratentoriellen Gliom mit einem standardisierten MRT-Protokoll untersucht. MRT-Untersuchungen erfolgten vor der neurochirurgischen Operation, möglichst innerhalb der ersten 3 Tage nach Operation und während der Nachbeobachtungszeit in Abständen von 2–3 Monaten. Die mediane Nachbeobachtungszeit betrug 11 Monate. Die initiale präoperative Ödemkonfiguration auf den T2-gewichteten MRT-Aufnahmen wurde mit der Rezidivtumorkonfiguration auf den Kontrastmittel verstärkten T1-gewichteten Aufnahmen verglichen. Ergebnisse: 47 Patienten entwickelten während der Nachbeobachtungszeit ein Rezidiv. Die Konfiguration des Rezidivtumors imitierte in 35/47 Patienten (75%) die initiale präoperative Ödemkonfiguration. Bei 11/47 Patienten entwickelte sich ein lokales und bei einem Patienten ein multilokales Rezidiv. Schlußfolgerungen: Die präoperative Tumorödemkonfiguration im T2-gewichteten MRT-Bild korreliert mit der Rezidivtumorausdehnung. Zukünftige Therapiestudien sollten daher die Ausdehnung des initalen präoperativen Ödems als zusätzlichen prognostischen Faktor mitberücksichigen.
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