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Biomedical subjects

I Baumann

Publications and source records attributed to I Baumann.

At least 55 records · Page 3Linked to original sources

Mobilisation kinetics of primitive haemopoietic cells following G-CSF with or without chemotherapy for advanced breast cancer.

BACKGROUND: The objective of this study was to determine the optimal conditions for blood progenitor cell harvest for transplantation, with main emphasis on the mobilisation kinetics of primitive, marrow repopulating cells. PATIENTS AND METHODS: Sixteen patients with advanced breast cancer were treated with 4 cycles of dose escalating FAC chemotherapy (5-fluorouracil, adriamycin, cyclophosphamide) each followed by 10 micrograms/kg/d G-CSF for 13 days. We assessed the number of colony-forming cells (CFC), and estimated the long-term culture initiating cells (LTC-IC) and CD34+ cells during the recovery phase of cycle 1 and 4 of chemotherapy, and during additional periods of G-CSF administration either preceding or following the full course of chemotherapy. RESULTS: The highest peak numbers of CFC per ml of blood (median 10489, range 860-39282) were mobilised after the first cycle of chemotherapy. The lowest peak numbers of CFC were obtained during the recovery phase from cycle 4 (median 4739, range 40-26789). In contrast, the numbers of CD34+ cells per ml of blood were significantly higher in cycle 4 (median 650, range 30-2600 x 10(2)) compared to those of cycle 1 (median 240, range 20-770 x 10(2)). The peak numbers of CFC mobilised by G-CSF before commencement and after the cessation of chemotherapy were equivalent, with a median of 5470 (range 1056-25669) and 5948 (range 2710-38975) per ml of blood, respectively. However, while mononuclear cells (MNC) collected at the days of maximal CFC mobilization following G-CSF administration before or after cycle 1 were similar to normal bone marrow MNCs in their ability to generate haemopoiesis when seeded onto performed irradiated stroma, those collected after cycle 4 or during G-CSF administration after the cessation of chemotherapy were markedly compromised in this respect. CONCLUSIONS: Our results indicate that repeated cycles of FAC chemotherapy followed by G-CSF result in a far lower number of LTC-IC than of CFC mobilised into the circulation. Furthermore although the combination of chemotherapy and G-CSF mobilised the highest numbers if CFC, G-CSF alone pre-chemotherapy was more effective at mobilising LTC-IC. These data indicate that neither the numbers of CFC mobilised nor the numbers of CD34+ cells are necessarily a reliable indicator for the putative marrow repopulating capability of the blood cells mobilised with chemotherapy plus G-CSF.

Adult↗

[Effect of breathing mode and nose ventilation on growth of the facial bones].

Correlations between breathing mode and craniofacial morphology were investigated in 47 children at the ages of 6-15 years (average, 9.9 years). Apart from history and clinical examination, nasal endoscopy, rhinomanometry and measurements of cephalometric radiographs were included in the analysis. After separating the patients into a "normal face" group and a "long face" group by measuring the angle between the frontal skull base and the mandibular plane, we analyzed the data in attempting to correlate nasal obstruction with craniofacial development. Findings demonstrated a significant predominance of mouth-breathing compared to nasal breathing in the vertical growth patterns studied. Furthermore, significant differences were found during nasal endoscopy in the growth pattern and were attributed to large adenoids. These findings were confirmed separately in all patients up to the age of 9 years, but differences were clearer. Rhinomanometry and planimetric measurements of the sizes of the adenoids in craniofacial radiographs showed no unambiguous differences between the patient groups. Our present study was not able to establish clear causal correlations between mouth-breathing, craniofacial development and adenoid size, suggesting that existing genetically determined craniofacial growth patterns are modulated by exogenic influences. Nonetheless, our results show a correlation between obstructed nasal breathing, large adenoids and vertical growth patterns.

Adenoids↗

Dose-escalating induction chemotherapy supported by lenograstim preceding high-dose consolidation chemotherapy for advanced breast cancer. Selection of the most acceptable regimen to induce maximal tumor response and investigation of the optimal time to collect peripheral blood progenitor cells for haematological rescue after high-dose consolidation chemotherapy.

BACKGROUND: In advanced breast cancer high-dose consolidation chemotherapy with haematological rescue has resulted in prolonged disease free and overall survival in a small percentage of patients. Maximal reduction of the tumor burden by intensive induction treatment preceding the high-dose chemotherapy may favor that outcome. The aims of this study were to find a rapid highly effective induction regimen with acceptable toxicity and to examine the optimal time for peripheral blood progenitor cell (PBPC) collection for haematological rescue. SUBJECTS AND METHODS: Twenty-four patients received 4 cycles of FAC chemotherapy (5-FU, adriamycin, cyclosphamide), each followed by 10 micrograms/kg/d of lenograstim (glycosylated rHuG-CSF) s.c. day 2 to 11. Chemotherapy was administered at 4 dose intensity levels with 6 patients including at each level (level 1: 500(F)/50(A)/500(C) mg/m2/3wk, level 2: 500/50/500 mg/m2/2wk, level 3: 500/75/500 mg/m2/2wk, m2/2wk, level 4: 500/75/1000 mg/m2/2wk d1 i.v.). In addition lenograstim (10 micrograms/kg/d s.c.) was administered for a period of 10 days before (period X) and after (period Y) chemotherapy. In 16 patients (4 at each dose intensity level) assessment of PBPC was performed during period X and Y as well as during cycle 1 and 4. A single apheresis to collect PBPC was planned during chemotherapy cycle 1. RESULTS: The best response was obtained at dose intensity level 3 (all 6 patients responded, 3 of them achieved CR) with acceptable toxicity. Peak circulating numbers of total CFC/ml blood were median 5819 (period X), 4635 (cycle 1), 3807 (cycle 4) and 3519 (period Y) and occurred concurrently with peak circulating numbers of CD34+ cells. The and median 3.76 x 10(6)/kg CD34+ cells. Three patients received high-dose consolidation chemotherapy with PBPC support. Recovery of ANC > 0.5 x 10(9)/l occurred on median day 11 and of platelets > 20 x 10(9)/l on median day 10. CONCLUSION: Dose intensity level 3 is the best usable induction regimen in this study. The optimal time for apheresis is either during lenograstim before chemotherapy treatment or during the first cycle of chemotherapy. Rapid haematological recovery was obtained by reinfusion of PBPC as sole source of support in the patients receiving high-dose consolidation chemotherapy.

Adult↗

Malignancy-associated changes in monocytes and lymphocytes in acute leukemias measured by high-resolution image processing.

A number of methods are available for classifying lymphoid and myeloid leukemias in peripheral blood and bone marrow. However, in clinical diagnosis an initial and particularly important step is morphologic analysis. All the cells in this investigation were classified by two hematologic experts. In most cases, immunophenotyping and immunocytochemical analyses were performed. Routinely prepared Romanowsky-Giemsa-stained peripheral blood smears (approximately 23,000 cells) were scanned by a high-resolution color TV/microscope system and analyzed by color and texture algorithms. In addition to blast cells, lymphocytes and monocytes exhibited a leukemia-associated change in morphology. The calculated texture and color features were most significant for the subtyping performed by the statistical program. With multivariate statistical analysis, seven mathematical subtypes of lymphocytes and five of monocytes could be found over all the specimens. Acute myeloblastic leukemia (AML, M1-M2), acute myelomonocytic leukemia (AMMOL, M4) and acute monocytic leukemia (AMOL, M5) could be differentiated by their distributions of monocyte subtypes. However, this was impossible for the lymphocyte subtypes. Acute lymphoblastic leukemias (B-ALL and T-ALL) were discernible with the aid of lymphocyte subtypes and acute myeloid conditions from viral infections, such as with the Epstein-Barr virus. The method increased the relevance of image processing in clinical diagnosis of acute leukemias and showed that the "normal" cell populations were not really normal in malignant leukemias.

Burkitt Lymphoma↗

Three-dimensional image processing for morphometric analysis of epithelium sections.

The reproducible classification of poorly differentiated abnormal epithelium specimens is still a diagnostic problem. The computer-aided method described here improves the differentiation between benign and malignant epithelium specimens. Hematoxylin and eosin-stained sections of normal squamous epithelium, dysplasia, carcinoma in situ, and carcinoma were scanned in a TV microscope system and analyzed by means of image processing methods on a DEC 5000/200 workstation. From the 15-20 microns thick histological sections, 3-5 focus positions in steps of 1-4 microns were scanned. The segmentation of the cell nuclei was performed automatically by color analysis and geometric operations. For each nucleus the best focus level was selected and at this level the center of the cell was calculated. Graph theoretical methods were applied to analyze the morphometry of the epithelium specimens. The minimal spanning tree was computed in the three-dimensional (3D) space of the sections with the selected centers of the nuclei as vertices. The best feature found for discrimination of the specimens is the average length of all edges in a tree. In the two-dimensional (2D) analysis we had to accept an error probability of about 20% in differentiation of dysplasia and carcinoma. In contrast to this we differentiated normal squamous epithelium, dysplasia, and carcinoma with a correct classification rate of 100% in the 3D analysis.

Carcinoma↗

Expression of Tac antigen component of bovine interleukin-2 receptor in different leukocyte populations infected with Theileria parva or Theileria annulata.

The Tac antigen component of the bovine interleukin-2 receptor was expressed as a Cro-beta-galactosidase fusion protein in Escherichia coli and used to raise antibodies in rabbits. These antibodies were used for flow cytofluorimetric analysis to investigate the expression of Tac antigen in a variety of Theileria parva-infected cell lines and also in three Theileria annulata-infected cell lines. Cells expressing Tac antigen on their surface were found in all T. parva-infected cell lines tested whether these were of T- or B-cell origin. T cells expressing Tac antigen could be CD4- CD8-, CD4+ CD8-, CD4- CD8+, or CD4+ CD8+. Tac antigen expression was observed both in cultures which had been maintained in the laboratory for several years and in transformed cell lines which had recently been established by infection of lymphocytes in vitro with T. parva. Northern (RNA) blot analysis demonstrated Tac antigen transcripts in RNA isolated from all T. parva-infected cell lines. Three T. annulata-infected cell lines which were not of T-cell origin were also tested. Two of them expressed Tac antigen on their surface. Abundant Tac antigen mRNA was detected in these T. annulata-infected cell lines, but only trace amounts were demonstrated in the third cell line, which contained very few Tac antigen-expressing cells. In all cell lines tested, whether cloned or uncloned, a proportion of the cells did not express detectable levels of Tac antigen on their surface. This was also the case for a number of other leukocyte surface markers. In addition, we showed that the interleukin-2 receptors were biologically functional, because addition of recombinant interleukin-2 to cultures stimulated cell proliferation. Recombinant interleukin-2 treatment also resulted in increased amounts of steady-state Tac antigen mRNA. The relevance of interleukin-2 receptor expression on Theileria-infected cells is discussed.

Animals↗

[Pattern analytic investigations of blast cells in myelodysplastic syndrome and secondary acute myeloid leukemia].

Blast-cells in Romanowsky-Giemsa stained bone marrow smears from 14 cases of primary myelodysplastic syndrome which consequently developed an acute myeloid leukemia and 28 cases of primary acute myeloid leukemia were analysed by a computer aided high resolution pattern recognition system. As control we used blast-cells from reactive affected bone marrow. Whereas blast-cell types in MDS and secondary AML showed overlapping features and a heterogenous distribution we could distinguish blasts in primary AML compared to "reactive" blasts. Opposite to this blasts in secondary AML showed no different pattern compared to "reactive" blast.

Acute Disease↗

[Function and pathology of bone marrow stromal cells].

For their lineage commitment and differentiation haematopoietic tem cells need a specific microenvironment. This milieu is formed by bone marrow stroma, which includes lymphocytes, macrophages, fibroblasts, reticular cells, adipocytes, osteogenic and endothelial cells. These cells play different regulatory roles in supporting haemopoiesis. The stroma-stem cell interaction take place by immediate cellular contact. Growth factors and extracellular matrix molecules produced by stromal cells influence the regulation of haemopoiesis as well. This cellular context could be established in different animal models. Impairment of stromal cell function with increased fibroblast proliferation and increased collagen synthesis is an impressive morphological feature of myelofibrosis.

Animals↗

[Experiences in the diagnosis and treatment of polyneuropathies in patients with malignant monoclonal gammopathy].

4 patients are reported having monoclonal gammopathies, who clinically exhibited a sensomotoric polyneuropathy being progressive during some years. The EMG showed axional failure and secondary demyelisation. In two of the patients an IgG-type multiple myeloma has been revealed, while in the other two ohnes an increase of abnormal IgM-mIg could be demonstrated. In all patients the liquor protein was found increased and the appropriate mIg has been found in the liquor. Immunohistochemically the appropriate immunoglobulins could be demonstrated on the peripheral nerve by means of immunofluorescence method. Electron microscopical studies of nerval biopsies supported the diagnosis of mIg-associated polyneuropathy. References to diagnostics and treatment of mIg-associated polyneuropathy are done.

Aged↗

A promising genomic transfectant into Xeroderma pigmentosum group A with highly amplified mouse DNA and intermediate UV resistance turns revertant.

Following transfection of genomic mouse DNA into an SV40 transformed fibroblast cell line from a patient with Xeroderma pigmentosum (complementation group A, XPA), a single UV resistant cell clone was isolated out of a total of 10(4) independent transfectants. The recipient XPA cell line has as yet not produced spontaneous revertants among 2.2 x 10(8) cells. The isolated cell clone contains 50-70 kb of mouse sequences which are heavily amplified (500-fold), and has acquired both intermediate resistance to UV killing and intermediate unscheduled DNA synthesis (UDS) capacity. By continued passage without selective pressure, cells were generated, which had lost both the dominant marker gene and repetitive mouse sequences. Single colonies of these cells were still intermediately resistant to UV suggesting that either undetected unique mouse DNA had segregated from the bulk of repetitive DNA, or, more likely, that the initially isolated transfectant was a spontaneous revertant. This documents that a persuasive clone isolated can still be a false positive (spontaneous revertant) and that an extremely laborious approach may lead into a dead end.

Animals↗

Infection with the intracellular protozoan parasite Theileria parva induces constitutively high levels of NF-kappa B in bovine T lymphocytes.

The intracellular protozoan parasite Theileria parva causes a lymphoproliferative disease of T cells in cattle and uncontrolled lymphocyte proliferation in culture. We have identified and characterized in infected cells the transcriptional activator, NF-kappa B, whose recognition motifs have been identified in several gene enhancers important for lymphocyte-specific gene expression. NF-kappa B is normally constitutively activated in nuclear extracts derived from B cells and can be induced in T cells and nonlymphoid cells by phorbol esters. Theileria-infected lymphocytes contained constitutively high levels of activated NF-kappa B in nuclear fractions and inactive NF-kappa B in cytoplasmic fractions. The inactive cytoplasmic precursor could be activated by treatment of extracts with deoxycholate, which was shown previously to dissociate NF-kappa B from an inhibitor, I kappa B. Treatment of lymphocyte extracts with 3 mM GTP stimulated NF-kappa B binding to its recognition motif in vitro, thereby distinguishing it from a related nuclear factor, H2-TF1. Selective killing of the parasite, which left the host cells intact, resulted in a rapid loss of NF-kappa B from the nuclear fractions and a slower loss from the cytoplasmic fractions. In parasitized cells, NF-kappa B could not be further stimulated by treatment with 12-O-tetradecanoylphorbol-13-acetate whereas in cells treated to remove the parasite, this compound stimulated elevated levels of NF-kappa B. We propose that high levels of activated NF-kappa B are maintained by the presence of the parasite in infected T cells. Similarly, we propose that the high levels of inactive cytoplasmic precursor are a result of increased synthesis due to the presence of the parasite.

Animals↗

[Low dosage retinol and L-cystine combination improve alopecia of the diffuse type following long-term oral administration].

In a pilot study (I) the efficacy of a new combination therapy for hair loss of the diffuse type was tested in 36 patients, followed by a double blind study with 47 patients. The daily dosage was 18,000 IE retinol, 70 mg L-cystine and 7000 mg gelatin. The clinical efficacy was evaluated by standard methods, such as the preparation of trichograms and measurement of the hair density before and after treatment. The pilot study demonstrated a significant improvement, with reduction of the telogen rate by 8.3%, an increase of the anagen rate by 11%, and an increase of the hair density by 6.9%. In the double blind study (II) the trichogram showed a significant decrease of the telogen rate by 13.5% compared with pathological baseline values. There was no change in the placebo group. The lowered anagen rate of 47.2% was improved by 8%, whereas the mean value in the placebo group decreased from 47.7% to 39.9%. In addition, the percentage of dysplastic anagen hairs improved by 7.4%, as against further impairment with an increase of 26% in the placebo group. During oral therapy no systemic side-effects were detected. We conclude that long-term oral therapy with high doses of L-cystine and gelatin in combination with vitamin A may have beneficial effects on diffuse hair loss.

Administration, Oral↗

[Testis endothesis surgery. Results of an ambulatory clinical evaluation study].

Under out-patient conditions 13 testicular endotheses of silicone rubber were implanted in local anaesthesia. The mean age of the 11 patients was 44.6 years and minimum follow-up was one year. In all but one case the clinical course was uneventful, in this patient the prosthesis was rejected after a secondary intervention. The follow-up examination did show in all cases clinical, ultrasonographical and cosmetical good results with the 14 g variant for the adult patient. This prosthesis is recommended the further use because of low operative risk, uneventful follow-up and improved body image.

Adolescent↗

12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.

Genomic clones coding for human fibroblast collagenase were isolated. By constructing and transfecting mutants with 5' and 3' deletion mutations of the 5' control region of the gene into human or murine cells, we delimited a 32-base-pair sequence at positions -73 to -42 which is required for the induction of transcription by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. The DNA element behaves as a 12-O-tetradecanoyl-phorbol-13-acetate-inducible enhancer: it mediates the stimulation of transcription to the heterologous herpes simplex virus thymidine kinase promoter and acts in a position- and orientation-independent manner. Differences in enhancer efficiency in different cell lines are interpreted to indicate differences in the activity of a trans-acting factor.

Adult↗

[Behçet disease and exogenous interferon. A successful treatment study using recombinant alpha-A-IFN].

Up till now no standard therapy for Behçet syndrome has existed. Long-term corticoid therapy is often necessary, although side-effects cannot be avoided. Recent investigations have shown a correlation between high endogenous gamma-interferon serum levels and low activity of the syndrome. A 20-year-old male with severe Behçet's syndrome was therefore treated with recombinant alpha-A-interferon (IFN). The general condition of the patient improved rapidly, together with rapid clearing of the skin lesions. Over a 10.5 week-period the patient received a total dose of 792 million IU recombinant alpha-A-interferon.

Behcet Syndrome↗