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Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 217 records · Page 12Linked to original sources
PubMed1992

A phase II study of high dose tamoxifen in progressive, metastatic renal cell carcinoma.

Thirty-four patients with progressive advanced renal cell carcinoma (RCC) were treated with high-dose tamoxifen (HD-TAM) 100 mg/m2 p.o. daily until progression. The overall remission rate was 12%, including 1 complete remission. Seventeen of the thirty-four (50%) patients had minor remission or no change. Taking into consideration the documented progression prior to tamoxifen therapy, further tumour growth could be arrested in 62% (1 CR, 3 PR, 17 MR/NC) of the patients. Median response duration for CR/PR was 20 months (range 6-21+) and median progression-free survival for MR/NC was 6 months (range 2-15). The one-year survival rate was 41%. Patients with only pulmonary metastases, good performance status and prior nephrectomy seemed to have a better survival. Side effects were comparable to those of conventional doses of tamoxifen (20-30 mg p.o. daily). These data suggest that HD-TAM may be a useful therapeutic approach with low toxicity, considering that, in metastatic RCC, the treatment intent is at best palliative.

Adult↗
PubMed1992

Evaluation of the valve area underestimation by the continuity equation.

During the last years, noninvasive determination of the aortic valve area by Doppler echocardiography using the continuity equation became popular. However, a systematic valve area underestimation of about 15% compared to invasive measurements using the Gorlin formula has been reported. The cause therefore is unknown. The purpose of this study was to evaluate whether the valve area underestimation by the Doppler method might be due to differences in the hydrodynamic background of both methods. This comparison is facilitated by the fact that the Gorlin formula is based on the continuity equation. Compared to the continuity equation, there are four changes within the Gorlin formula: (1) the additional use of a discharge coefficient, which leads to valve area overestimation by the factor 1.17; (2) neglect of the pre-stenotic velocity, causing further overestimation by the factor 1.036 (in mild stenosis this factor may be 1.18 and more); (3) the wrong calculation of the mean pressure drop, which leads to a mean change by the factor 0.95, and (4) the incorrect substitution of the height by the pressure drop in the derivation of the Gorlin formula causes underestimation by the factor 0.97. Combining these four factors results in valve area overestimation of the Gorlin formula compared to the continuity equation by the factor 1.12. This explains to a large extent the valve area underestimation by the continuity equation.

Aortic Valve↗
PubMed1992

Change in surface hardness of BisGMA/TEGDMA polymer due to enzymatic action.

The surface microhardness of specimens made of a BisGMA/TEGDMA polymer was measured before and during treatment for 60 days with phosphate buffer or phosphate-buffered esterase solution with an activity corresponding to the mean hydrolase activity of human saliva. The hardness of the buffer-treated specimens was unchanged during the incubation period, while that of the esterase-treated specimens decreased gradually. After about five days of treatment, no further change in hardness was observed for up to 60 days. Based on the difference in the calculated hardness of the specimens as a function of the applied load during measurement, it was estimated that the mean microhardness of the outermost surface layer of the esterase-treated specimens was diminished by about 15%, compared with that of the buffer-treated specimens. From these results, it was concluded that the wear resistance of a BisGMA/TEGDMA polymer is most likely diminished by hydrolases in saliva.

Analysis of Variance↗
PubMed1992

Karyotype instability in myelodysplastic syndromes--a specific step in pathogenesis preceding clonal chromosome anomalies.

In a prospective study, 20 (11.6%) out of 172 patients with myelodysplastic syndromes (MDS) and two patients with aplastic anemia showed an increased spontaneous karyotype instability. No clonal chromosomal aberrations were detectable at the time of first examination. In three patients clonal anomalies developed during the course of the disease. In 17 out of 22 cases (77.2%) chromosomes 1, 5 or 7 were involved in nonclonal anomalies. The same chromosomes were frequently affected in patients with clonal abnormalities too. Our data suggest that spontaneous karyotype instability may be specific to a high proportion of cases with MDS and may constitute the source of clonal chromosome anomalies in these disorders.

Adult↗
PubMed1992

Quantitative image analysis of angiogenesis in rats implanted with a fibrin gel chamber.

Angiogenesis, a fundamental process in various physiological and pathological events, is generally studied using in vivo models, such as the chick chorioallantoic membrane or the rabbit cornea, which are difficult to quantitate. We developed the quantitation of angiogenesis in an in vivo model previously described by Dvorak et al [6]. Perforated plexiglass chambers filled with human or rat fibrin were implanted into the dorsal subcutaneous space of a Wistar rat. After four days of implantation, a sequentially organized invasion of the fibrin gel by various blood cell types occurred through the holes and neovascularized granulation tissue buds appeared. These buds presented mature neovessels and a new collagen matrix. Three dimensional computer image analysis of the chambers was performed using macroscopic and microscopic parameters: total vascularized area, bud height and equivalent diameter, number of vessels per bud and percentage of central vessels. The time course of the angiogenic response to rat or human fibrin gel was studied and 14 days was found to be the optimum period of implantation. The bud height and number of neovessels were not found to be significantly different when rat or human fibrin gels were used. This quantitative study was a prerequisite for further investigations of the effects of biological and pharmacological agents on angiogenesis.

Animals↗
PubMed1992

Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients.

In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61). The histopathology of bone marrow biopsies revealed hyperplasia and disturbed differentiation in megakaryopoiesis; the frequency and grade of dysplasia in megakaryopoiesis increased with advancing myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelo-monocytic leukaemia (CMMoL). The frequency of cytogenetic aberrations was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly lower values of haemoglobin and lower platelet counts in MDS with myelofibrosis. Life expectancy was reduced to 9.6 months, compared with 17.4 months in MDS without fibrosis. In refractory anaemia, the survival times were 10.0 months in MDS with myelofibrosis, compared to 28.9 months in MDS without myelofibrosis. 36.6% of the patients with MDS and myelofibrosis developed a transformation into ANLL during the course of the disease. Myelofibrosis therefore seems to herald a poor prognosis.

Adult↗
PubMed1991

Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes?

Cytogenetic and clinical data of 11 patients with de novo myelodysplastic syndromes and partial or total trisomy of the long arm of chromosome 1 are presented. In eight of these patients trisomy 1q was the sole karyotypic change and therefore can be classified as a primary chromosome anomaly. A remarkably young median age of 36.5 years was noticed in this patient group.

Adolescent↗
PubMed1991

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

OBJECTIVE: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. DESIGN: Retrospective comparison of two cohorts of patients. SETTING: Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. PATIENTS: Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. MAIN RESULTS: Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. CONCLUSIONS: These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.

Adolescent↗
PubMed1991

Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group.

BACKGROUND AND METHODS: Immunosuppression is the most effective treatment for patients with aplastic anemia, except for bone marrow transplantation. The best results are achieved with antilymphocyte globulin or cyclosporine. Patients have been treated successfully with a combination of both agents, but there has been no controlled evaluation of its efficacy. We conducted a randomized, multicenter trial in 84 patients not eligible for bone marrow transplantation, comparing treatment with antilymphocyte globulin and methylprednisolone (41 patients--the control group) with antilymphocyte globulin, methylprednisolone, and cyclosporine (43 patients--the cyclosporine group). RESULTS: At three months significantly more patients in the cyclosporine group had a complete or partial remission in response to treatment than did patients in the control group (65 percent vs. 39 percent, P less than 0.03); this difference was confirmed at six months (70 percent vs. 46 percent, P less than 0.05). The superior results of the regimen including cyclosporine were most evident in the patients with severe or very severe aplastic anemia, whose response rate at six months was 65 percent, as compared with 31 percent of such patients in the control group (P less than 0.02). Granulocyte and hemoglobin levels became normal in most patients who responded, but platelet counts continued to be subnormal in 61 percent of the patients. Ten of 52 patients with responses (3 in the cyclosporine group and 7 in the control group) relapsed 4 to 37 months after treatment. The actuarial survival of all patients at 41 months is 64 percent in the cyclosporine group and 58 percent in the control group (P = 0.16); among the patients with severe or very severe disease, survival is 80 percent and 44 percent, respectively (P = 0.077). Cyclosporine had substantial but reversible side effects. CONCLUSIONS: Immunosuppressive treatment of aplastic anemia with antilymphocyte globulin, methylprednisolone, and cyclosporine appears to be more effective than a regimen of antilymphocyte globulin and methylprednisolone without cyclosporine and may thus represent a treatment of choice for patients who are not eligible for bone marrow transplantation.

Adult↗
PubMed1991

High-dose ara-C and etoposide in refractory or relapsing acute leukemia.

A total of 32 patients (15 men and 17 women) presenting with relapsing or refractory acute leukemia were treated with a 3-h infusion of 3 g/m2 cytosine arabinoside (ara-C) twice daily on days 1-6 and a 1-h infusion of 100 mg/m2 etoposide on days 1-5. In all, 6 subjects had acute lymphocytic leukemia (ALL); 25 had acute myeloid leukemia (AML) of types M1 (n = 6), M2 (n = 10), M4 (n = 5), and M5 (n = 4); and 1 had mixed-type leukemia. The median age was 35 years (ranges, 16-62 years). Of the patients presenting with AML, 11 were primarily refractory and 3 became refractory after their first relapse. Six subjects had an early first relapse following a complete remission (CR) that lasted less than 6 months and five, a second relapse. Another patient underwent a primary relapse after greater than 6 months but had been heavily pretreated. In all, 5 subjects with refractory AML achieved a CR (36%; 95% confidence interval (CI), 10%-62%) as did 7 patients exhibiting relapsing AML (58%; CI, 30%-86%). Three patients who had relapsing or resistant ALL achieved a CR. Side effects consisted of severe hematotoxicity associated with granulocytopenia of less than 500/mm3 that lasted for a mean of 23.6 days and thrombocytopenia of less than 20,000/mm3 whose mean duration was 20.8 days. Marked gastrointestinal toxicity and infections were also prevalent. Cutaneous and ocular toxicity as well as allergic, pulmonary and cerebellar side effects were observed in a few cases. We conclude that the combination of high-dose ara-C and etoposide is a powerful but toxic induction regimen for refractory or relapsed acute leukemia.

Acute Disease↗
PubMed1991

Five-day 4'-(9-acridinylamino)methanesulphon-m-anisidide and intermediate-dose cytosine arabinoside in high-risk relapsing or refractory acute myeloid leukemia.

Twenty-two patients with acute myeloid leukemia (AML), having a median age of 48.3 years (range 26-70; 10 male, 12 female), were treated with 4'-(9-acridinylamino) methanesulphon-m-anisidide (m-AMSA) 100 mg/m2 and cytosine arabinoside (AraC) 2 x 1000 mg/m2i.v. on days 1-5. There were 2M1,8 M2, 9 M4, 2M4 Eo, and 1 M5a. Of these, 12 achieved a complete remission, 3 a partial remission and 6 did not respond. The median remission duration was 9.0 months and the median overall survival 8.1 months. Side-effects of induction consisted mainly of haematological toxicity and infections with a median duration of WHO-grade-4 granulopenia and thrombopenia of 20 and 28 days respectively. Organ toxicity was mild with mucositis and cutaneous and liver toxicity being experienced by only a few patients. There was one treatment-related death. Five-day m-AMSA and intermediate-dose AraC is an easy-to-handle condensed treatment schedule with tolerable toxicity. Its effectiveness in relapsed and refractory AML is comparable to combinations of high-dose AraC with m-AMSA, anthracyclines or etoposide.

Acute Disease↗
PubMed1991

Treatment of advanced chronic lymphocytic leukemia by fludarabine. Results of a clinical phase-II study.

In a clinical phase-II study fludarabine phosphate was given to 20 patients with advanced chronic lymphocytic leukemia who had failed on prior conventional therapy. Fludarabine was administered at a dose of 25 mg/m2/d for 5 days. Treatment cycles were repeated every 4 weeks until maximal response, followed by two cycles for consolidation. Four of the 20 patients achieved complete remission and seven patients partial remission, resulting in an overall response rate of 55% (11/20). Fludarabine therapy was well tolerated, with mild myelosuppression and secondary infections comprising the predominant side effects. These data warrant further confirmation and a randomized comparison of fludarabine with established regimens, which is currently underway.

Adult↗
PubMed1991

Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha.

Of 38 patients with a Philadelphia-chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN-alpha) 2a or 2b and monitored for emergence of IFN-antibodies in their sera 11 patients developed rIFN-alpha 2 binding and 10 rIFN-alpha 2 neutralizing antibodies. rIFN-alpha neutralizing antibody positive patients experienced significantly (P less than 0.025) more clinical relapses (6/10) than IFN-antibody negative patients (6/28) during continuous IFN-therapy. Furthermore, IFN-antibody-positive patients with titre above 400 INU/ml were more likely to relapse under rIFN-alpha-therapy than IFN-antibody-negative patients with titre below 400 INU/ml (P less than 0.05). Seven rIFN-antibody-positive patients experiencing a clinical relapse or a primary non-responsiveness were treated with two- to three-fold increased doses of rIFN-alpha 2. Only one of these seven patients developed a partial haematological remission upon intensification of the rIFN-alpha 2 therapy. Consecutively, the six patients failing high dose rIFN-alpha treatment were switched to a natural IFN-alpha preparation (3 x 9 x 10(6) I.U. weekly s.c.). Under such treatment two of the six patients achieved a long-lasting complete, one a partial haematological remission. In high-titred IFN-antibody positive patients significantly altered serum-IFN-titre and minimal IFN-inducible Mx-homologue concentrations were measured; in contrast, nIFN-alpha induced normal IFN-titre and dose-equivalent Mx-homologue amounts in these patients. The data prove that high-titred rIFN-alpha neutralizing antibodies abrogate the biological action of rIFN-alpha, but not of nIFN-alpha in vivo and explains why nIFN-alpha can be effective in the anti rIFN-alpha 2 positive patients.

Antibodies, Neoplasm↗