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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 497 (1989), S. 302-307 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biology of the Cell 64 (1988), S. 23-28 
    ISSN: 0248-4900
    Keywords: cell proliferation ; flow cytometry ; monoclonal antibodies ; surface and nuclear proteins
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Lung cancer ; Granulocyte-macrophage colony-stimulating factor ; Chemotherapy ; Bone marrow myeloid cell kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Information on the kinetics of bone marrow (BM) myeloid precursors (BMMP) is required for integrating cancer chemotherapy with granulocyte-macrophage colony-stimulating factor (rhGM-CSF), with the aim of reducing neutropenia. Using bivariate flow-cytometric analysis of the in vivo incorporation of bromodeoxyuridine (BUDR) vs DNA content we have studied the kinetics of BMMP in 21 patients with SCLC during the first of six chemotherapy courses (etoposide, epirubicin, andcis-platinum, days 1–3, every 21 days), given alone (eight patients) or followed by rhGM-CSF (10μg/kg/day s.c, days 4–14) as BM rescue (eight patients) or both preceded (days -17 to -7, as BM priming) and followed by rhGM-CSF (five patients). At 11–14 days after the start of these therapies there was an increase in the baseline proliferative activity of proliferating BMMP and a shortening in the time needed by the metamyelocyte to mature and to leave the marrow. Both effects were greater and were maintained to a significantly greater degree a week later in patients who received chemotherapy plus rhGM-CSF rescue than in those who received chemotherapy alone or rhGM-CSF priming alone. At day 11–14 the pretreatment median cell production rate of pBMMP was increased by 340%, 150%, and 183% and the maturation time was reduced by 80%, 45%, and 57%, respectively, in the three groups. A week later, the corresponding figures were 206%, 111%, and 157% and 50%, 18%, and 45%. Hence, an identical rhGM-CSF schedule is more effective in increasing the neutrophil production by BMMP when given following chemotherapy as BM rescue than before it as BM priming. In both the rescue and the priming schedule, the increase in proliferative activity of BMMP just at the end of rhGM-CSF stimulation was linked to both an increase in the labeling index and a reduction in duration of S-phase (TS), while a week later it was linked solely to reduction in TS. This could actually reduce one of the two kinetic targets of subsequently administered cytostatics, i.e., a high LI and a long time spent in S phase. From this study, accurate kinetic data can be obtained with the in vivo BUDR technique that are useful in scheduling rhGM-CSF.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Essential thrombocythemia ; Interferon-α ; Sustained remission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In essential thrombocythemia patients α-IFN rapidly reduces platelet count, and it is also able to maintain a low count during long-term treatment. In order to verify if long-term IFN treatment can produce sustained remission in selected patients, we decided to suspend IFN treatment in two subsets of 21 patients on long-term α-IFN treatment: (a) all six patients who had shown a platelet count below 450×109/l for at least 2 months with 3 MU once a week; (b) three patients who had shown the same platelet count for at least 2 months with 3 MU three times a week. After withdrawal of α-IFN treatment, a rapid increase in the platelet count was observed in all three patients requiring 3 MU three times a week. Three of the six patients treated with 3 MU once a week are still free of symptoms and have been in complete hematological remission (platelet count below 450×109/l) for 9+, 13+, and 14+ months, respectively. As far as the three remaining cases are concerned, one was not assessable because of loss to follow-up, while the other two relapsed after 1 and 2 months. We believe that the three cases of sustained remission might be the result of a long-term tumor load reduction produced by the α-IFN treatment. Finally, the factor best able to predict sustained, unmaintained remission seems to be the clinical response to a low dose of α-IFN during the maintenance phase, rather than disease features prior to treatment.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: Essential thrombocythemia ; Interferon alpha ; Long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600×109/l in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600×109/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: α-IFN ; Phlebotomy ; Polycythemia vera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Interferon alpha (α-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid α-IFN (α n−1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of α n−1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during α-IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of α-IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that α-IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0584
    Keywords: Cell kinetics ; Congenital Dyserythropoietic Anemia ; Quantitative 14-C Autoradiography ; Ineffective Erythropoiesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The proliferation kinetics of erythropoiesis and of myelopoiesis have been studied in a case of congenital dyserythropoietic anemia type II (HEMPAS) by means of quantitative 14-C autoradiography, Feulgen cytophotometry and 59-Fe ferrokinetics. Increased total erythropoietic activity and ineffective erythopoiesis was demonstrated by ferrokinetics. Quantitative 14-C autoradiography showed a generally delayed proliferation rate of erythroid cells, most evident in the polychromatic compartment. A deficiency of cell production of 25% was detected among the polychromatic erythroblasts. Part of this fraction is represented by cells still capable of passing to the successive stages of maturation. We conclude that only part of the deficiency of cell production in the polychromatic compartment represents real cell destruction. Most of the measured ineffectiveness is confined to later stages of maturation, such as orthochromatic erthroblasts and marrow reticulocytes.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: Refractory cytopenias ; FAB classification ; Bone marrow cellularity ; Androgen therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One hundred and one patients with refractory cytopenia were reviewed for morphological classification (using bone marrow, BM, imprints for cytology and Jamshidi biopsies for BM cellularity) and clinical course. Final diagnoses were: moderate aplastic anemia (MAA), myelodysplastic syndromes (MDS) and hypoplastic acute leukemia (HAL). Ninety-two patients received high dose testosterone enanthate (TE) as first treatment (starting dose=7–10 mg/week i.m. for at least three months). Median survival was significantly longer in MAA than in MDS and in HAL. Among MDS patients, those with primary acquired sideroblastic (AISA) and refractory (RA) anemia had median survival similar to those with MAA, but distinctly longer (p=0.01) than patients with RA with an excess of blasts (RAEB), RAEB in transformation (RAEBtr) and chronic myelomonocytic leukemia (CMMoL). Acute leukemia (AL) developed more rarely (p〈0.02) in MAA, AISA and RA than in RAEB, RAEBtr and CMMoL. Response to TE was seen in about two thirds of MAA and in a half of MDS and HAL patients. Among MDS patients, those with hypocellular BM developed leukemia less frequently, responded to androgens more often and survived longer than those with normocellular and, especially, with hypercellular BM. These data indicate that the cytohistological classification of refractory cytopenias identifies essentially two groups with different clinical behaviour, one (MAA, AISA and RA) having long life expectancy and a low probability of developing AL and the other (RAEB, RAEBtr, CMMoL) with a short survival and relatively frequent leukemic complication. Bone marrow hypocellularity seems to be a favourable prognostic factor in MDS. Patients with refractory cytopenias, especially those with a hypocellular BM, can be advantageously treated with androgens.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pharmacokinetics of carboplatin in cerebrospinal fluid (CSF) and plasma was studied in five children with brain tumors (four medulloblastomas and one ependimoblastoma) who underwent preirradiation treatment with carboplatin. Carboplatin pharmacokinetics was studied following the administration of 600 mg/m2 as a 1-h infusion. Four children were treated a few weeks after surgery, whereas one child with an unresectable tumor was treated prior to surgery. All patients had a ventricular-peritoneal CSF shunt connected to a subcutaneous reservoir. Total platinum and free carboplatin were measured. The mean AUC values for free carboplatin in CSF and plasma were 2.29±1.20 and 8.18±1.27 mg ml−1 min, respectively. The mean ratio of CSF AUC to plasma AUC was 0.28 (range, 0.17–0.46). Both plasma peak levels and AUC values showed limited interpatient variability. On the other hand, carboplatin levels in CSF showed substantial interpatient variability, with a〉5-fold difference in peak levels and a 3-fold difference in AUC values being recorded. The interpatient difference in CSF pharmacokinetics may have been related at least in part to the different anatomical alterations induced by the surgical procedures or by the presence of a large tumor mass. In the four evaluable patients exhibiting macroscopic residual tumor, we observed one complete remission (CR) and two partial remissions (PR) following two cycles that consisted of two doses of 600 mg/m2 carboplatin given on 2 consecutive days (total dose, 1200 mg/m2) and were separated by a l-month interval. These results may give some indication as to the optimal dose and schedule for carboplatin administration in the treatment of primitive neuroectodermic tumors (PNET).
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta mechanica 133 (1999), S. 39-56 
    ISSN: 1619-6937
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Summary In this paper, a generalized self-consistent method is proposed to predict the effective moduli of a material containing single-phase and randomly oriented spheroidal inclusions, with same aspect ratios. This is achieved by using an energy equivalence framework, associated with a generalization of the classical three phase model to spheroidal inclusions. The localization problem (spheroidal duplex inclusion problem) is formulated with the Papkovitch-Neuber approach; this requires expansion formulae for the spheroidal potentials, which are derived in the Appendix. Finally, the determination of the effective moduli is equivalent to solving a system of nonlinear equations. Effective moduli are presented for various types of inclusions, and comparisons are made with the estimations obtained from the self-consistent and Mori-Tanaka methods. Moreover, the effects of inclusion geometry and spatial distribution of inclusions on the effective moduli are investigated and compared to each other.
    Type of Medium: Electronic Resource
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