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Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 253 records · Page 14Linked to original sources
PubMed1990

[Detection of cells with phenotype of multiple drug resistance in myeloproliferative disorders before the treatment].

The expression of the multidrug resistance (MDR) phenotype is connected with the overexpression of P-glycoprotein. By applying the immunocytochemical assay we have demonstrated that in myeloproliferative diseases (AML, ALL, MDS, CGL), in single cases, in smear preparations from the peripheral blood and bone marrow the cells with MDR-positive phenotype can be detected in the material obtained from patients before therapy, and without clinically and anamnestically known exposure to cytotoxic or immunosuppressive drugs. This finding has demonstrated the presence of subpopulations of MDR-positive cells in leukemias and myelodysplastic syndromes already before therapy, and, furthermore, has evidenced that a positive MDR phenotype is not necessarily associated with a malignant phenotype of a malignant cell transformation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralizing anti-interferon antibodies.

Twenty-seven patients with Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase were treated with low doses of recombinant interferon (IFN) alpha-2b. Ten patients entered a complete and six a partial haematologic remission with a median duration of 5.8 and 9.1 months respectively. Five minor cytogenetic responses were observed. These results are inferior compared to other studies with higher interferon-doses. Fever was an acute side effect after injection of IFN, limb pains and fatigue occurred protractedly. Haematologic side effects, nonspecific EEG changes, weight loss, and development of pulmonary infiltrates were observed in later periods of the treatment. Eight patients developed neutralizing anti-IFN antibodies after 4.2-20.4 months (median 12.8 months). Anti-IFN antibodies were associated with relapse or refractoriness to IFN treatment: five out of nine patients with rising WBC after initial fall had antibodies, while four did not. Two out of four patients with primary non-response had IFN-antibodies. These results may indicate a serious problem in the long-term treatment of CML with recombinant interferon.

Adolescent↗
PubMed1989

Detection of cells with multidrug-resistant phenotype in myeloproliferative disorders before therapy.

The expression of the multidrug resistance (mdr) phenotype is connected with the overexpression of the P-glycoprotein. By applying the immunocytochemical assay, we have demonstrated that in myeloproliferative diseases (AML, ALL, MDS, CGL) in single cases in smear preparations from the peripheral blood as well as from the bone marrow P-glycoprotein-positive cells, respectively, cells with mdr-positive phenotype can be detected in the material obtained from patients before therapy and without clinically and anamnestically known exposure to cytotoxic or immunosuppressive drugs. In the control group of probands without hematologic disorders and also without clinically or anamnestically confirmed contact with cytotoxic or immunosuppressive drugs, we have found P-glycoprotein-positive subpopulations of cells with positive mdr phenotype in a few cases as well. The uniqueness of our results lies in the fact that this finding demonstrates the presence of subpopulations of mdr-positive cells in leukemias and myelodysplastic syndromes before therapy, and furthermore makes evident that a positive mdr phenotype is not necessarily associated with a malignant phenotype or a malignant cell transformation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Humoral response to recombinant interferon-alpha 2b in patients receiving recombinant interferon-alpha 2b therapy.

Twenty-seven patients in the chronic phase of a Philadelphia chromosome-positive chronic myelogenic leukemia (CML) underwent a monotherapy with recombinant interferon-alpha 2b (rIFN-alpha 2b), receiving a mean dose of 3 x 5 Mio. IU per week. Eight of the 27 patients developed both rIFN-alpha 2b-binding and -neutralizing antibodies during therapy. Sera of these patients abrogated both antiviral and antiproliferative activities of rIFN-alpha 2b, but not of nIFN-beta or rIFN gamma. Only one serum neutralized nIFN-alpha. The IFN binding and neutralizing titers rose during therapy, while a decrease occurred over months after cessation of therapy. The IgG fraction obtained by DEAE chromatography contained more than 90% of the IFN-neutralizing capacity of the purified sera. This result strongly suggested that IgG antibodies are responsible for the IFN-alpha-neutralizing activity.

Antibodies↗
PubMed1988

Prenatal diagnosis of Hunter syndrome using fetal plasma.

The X-linked Hunter syndrome or mucopolysaccharidosis II was diagnosed in a male fetus by demonstrating a severe deficiency of iduronate 2-sulphate sulphatase activity in fetal plasma obtained by umbilical fetal blood sampling at 23 weeks of pregnancy. The diagnosis was confirmed after termination of pregnancy.

Female↗
PubMed1988

Treatment with natural human interferon alpha of a CML-patient with antibodies to recombinant interferon alpha-2b.

A patient with Philadelphia-chromosome positive chronic myelogenous leukemia developed interferon antibodies on treatment with recombinant interferon alpha-2b. Clinically this event corresponded with progressive disease. No cross-reactivity of antibodies with human leukocyte interferon was found by Western blot. Treatment was switched to human leukocyte interferon with an obvious clinical effect: WBC was reduced and platelet count stabilized, but the effect was transient and no hematologic remission was achieved. Human leukocyte interferon may be an alternative in CML-patients with neutralizing antibodies to recombinant interferon alpha.

Antibody Formation↗
PubMed1988

[Induction and intensive combined therapy of acute myeloid leukemia in adults].

In a prospective multicenter study the efficacy and toxicity of an induction therapy with daunorubicin, cytosine-arabinoside and VP 16-213, followed by an intensified consolidation with high-dose cytosine-arabinoside and daunorubicin, is evaluated in adult patients with acute myelogenous leukemia. The upper age limit for inclusion in the study was 50 years. Within the first two years of this study 91 patients were enrolled. In 84 patients who have finished the remission induction therapy the rate of complete remissions is 67%. The median survival time of all patients is 22 months and the probability of survival is 46% after 24 months. So far 34 patients in complete remission have been given one or two courses of the intensified consolidation therapy with high-dose cytosine-arabinoside and daunorubicin. The probability of relapse-free survival in these patients is 46% after 22 months and the median remission duration is 20 months.

Adolescent↗
PubMed1988

Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen.

Both mitoxantrone and etoposide have been shown to be active in monotherapy trials of relapsed and refractory acute myelogenous leukemia (AML). This phase II study was undertaken to assess the antitumor activity and toxicity of the combination in refractory and poor-risk AML. The regimen consisted of mitoxantrone, 10 mg/m2/d intravenously (IV), and etoposide, 100 mg/m2/d as short infusion, both on days 1 to 5. Sixty-one patients are evaluable for response and toxicity. Twenty-one were primarily refractory to conventional courses of cytarabine, daunorubicin, and thioguanine; 20 patients had poor-risk first relapse (relapse within 6 months of first complete remission [CR] or relapse under continuous maintenance therapy); 11 had second or subsequent relapses; and nine developed secondary AML after myelodysplastic phase or myelofibrosis. Twenty-six patients (42.6%) attained a CR and seven (11.5%) a partial remission (PR). The median duration of continuous CR was 4.7 months, with a range of 21 days to 14 months, excluding four patients who underwent autologous bone marrow transplantation. Severe myelosuppression was observed in all patients, with a median time to CR of 49 days. Nonhematologic toxicity included stomatitis (mainly grade 1 and 2) in 41 patients, nausea (mainly grade 1 and 2) in 44, infections (mainly grade 3) in 33, and fever of unidentified origin in 11. Other than transient, mild cardiac failure in nine patients, in some of them combined with grade 1 to 2 tachyarrhythmia, no other drug-related cardiac events were observed. Two cases of early death within the first 6 weeks of treatment were registered. Thus, the combination of mitoxantrone and etoposide is a highly active and well-tolerated regimen for refractory and poor-risk AML.

Adolescent↗
PubMed1988

Folinic acid (FA) plus 5-fluorouracil (FU) in progressive advanced colorectal cancer.

Treatment results (CR/PR** 30-40%) with the combination of 5-FU and FA--a biomodulator of 5-FU action--indicate that FA/5-FU is superior to 5-FU alone in the treatment of advanced colorectal cancer. However the "optimal" dose and time schedule has not been properly defined either for FA or for 5-FU. Moreover, in spite of the promising reports with FA/5-FU, the benefit of chemotherapy in colorectal carcinomas remains unproven. One way to better define the impact on survival and palliation might be to select patients with a documented tumor progression prior to chemotherapy. In 2 prospective phase II studies with FA/5-FU, tumor progression was the essential eligibility criterion. In both studies an overall tumor control (CR/PR/MR/NC)** of progressive disease with relief of tumor-related symptoms in most of the patients was achieved. The median survival times exceeded 12 months. In progressive colorectal cancer these treatment results can be regarded as a significant change in the natural history of the disease. Moreover, such a procedure will help to define more homogeneous patient groups and contribute to a better comparability of different studies. Additionally, overtreatment of patients with slowly proliferating tumors can be avoided, particularly with respect to the subjective and objective side-effects of FA/5-FU combinations.

Antineoplastic Combined Chemotherapy Protocols↗