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Biomedical subjects

W Schultze

Publications and source records attributed to W Schultze.

At least 19 recordsLinked to original sources

High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial.

PURPOSE: Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes. PATIENTS AND METHODS: Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival. RESULTS: After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths). CONCLUSION: There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.

Adult↗

The moss Physcomitrella patens releases a tetracyclic diterpene.

The presence of the tetracyclic diterpene 16alpha-hydroxykaurane (16alpha-hydroxy-ent-kaurane, C20H34O, CAS 5524-17-4) was detected in sterile cell cultures of the moss Physcomitrella patens (Hedw.) B.S.G. using gas chromatography and mass spectrometry. 16alpha-hydroxykaurane was found to be a major lipid compound in P. patens, with an estimated intracellular concentration of up to 0.84 mmol/l and an extracellular concentration of up to 9.3 micromol/l. The overall content of 16alpha-hydroxykaurane (in milligrams) produced per culture reached 0.37-fold that of chlorophyll a+b. In agar cultures with low air exchange, 16alpha-hydroxykaurane forms needle-like crystals on tissue and on the inner surface of the culture vessels, indicating that it is being released into the atmosphere. Solid phase microextraction confirmed the air-bound release of 16alpha-hydroxykaurane. To our knowledge this is the first report on the release of a plant-derived tetracyclic diterpene into the air.

Bryopsida↗

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Adolescent↗

Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95.

Semaphorins are a family of secreted and membrane-associated proteins involved in growth cone guidance during development. Here, we describe the interaction of Semaphorin4F (Sema4F) with the post-synaptic density protein SAP90/PSD-95. Using the yeast two-hybrid system and coprecipitation assays we were able to show an interaction between the extreme C-terminus of Sema4F and the PDZ domains of SAP90/PSD-95. Heterologous coexpression of a chimeric EphrinB1/Semaphorin4F protein with SAP90/PSD-95 in COS cells leads to translocation of SAP90/PSD-95 from the cytosol to the membrane. Deletion analysis shows that this translocation activity of Sema4F is completely dependent on the presence of the last three C-terminal amino acids. In addition, Sema4F immunoreactivity is present in synaptosome fractions and enriched in post-synaptic density fractions. Consistently, in cultured hippocampal neurons, we demonstrate punctate colocalization of Sema4F and SAP90/PSD-95 in dendrites, furthermore we found colocalization of Sema4F with synapsin1 suggesting a synaptic localization. Our data implicate a new functional context for semaphorins at glutamatergic synapses.

Amino Acid Sequence↗

[Antifungal susceptibility testing in chronically recurrent vaginal candidosis as basis for effective therapy].

The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn problematic diagnosis in the dermatology and gynaecology ward. Prognosis and therapy are primarily determined by the causative micro-organism and the interaction of the fungal species with the currently available antifungal agents. Objective of the study was the investigation of vaginal yeast isolates from patients with chronically recidivist vaginal candidiasis against 8 antifungal agents with the aim of optimising the standard therapy with azole antifungal agents and assessment of alternative therapy schemes. 55 clinical isolates (Dermatology, Charité) of 40 patients were tested by microdilution according to DIN 58940-84. Species differentiation and identification was performed by Fourier-Transform Infrared Spectroscopy (FTIR). In the result Candida glabrata was the predominant causative agent for the recidivist vaginal candidiasis. MIC-mode values for C. glabrata were: fluconacole 32 micrograms/ml, itraconacole 1 microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03 microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml, cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml. Some strains of Patients with suboptimal introductory low doses of fluconacole showed increasing of MIC in course of therapy. Parallel resistance with itraconacole was observed in all these cases. Consecutively isolated strains could be clearly and reliably identified by FTIR. In conclusion of most importance is the initial dose adapatation of the drug used, e.g. for fluconacole 800/d p.o., when C. glabrata is the causative agent. Low dose fluconacole therapy is always unsuccessful in recurrent vaginal candidiasis and induces secondary resistance. Demonstrated high susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly for C. glabrata may indicate of an anitmycotic therapy potential unconsidered regarding to dermatological indication up to now.

Amphotericin B↗

The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis.

Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range of MNCs suitable for transplantation (10 to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at > 0.7 x 10(6)/graft) determined the yield of human cells produced in recipient animals. Engraftment of hu PBSC preparations resulted in prolonged generation of physiologic levels of human cytokines including interleukin-3 (IL-3), IL-6, and granulocyte-macrophage colony-stimulating factor, which were detectable in the murine blood over a period of at least 4 months. In vivo survival of immature human progenitor cells was preserved even 9 months after transplantation. Because human IL-3 is known to stimulate early hematopoiesis, a rat fibroblast cell line was stably transfected with a retroviral vector carrying the human IL-3 gene and cotransplanted subcutaneously as additional source of growth factor. Cotransplants of this cell line producing sustained in vivo levels of circulating human IL-3 for at least 12 weeks significantly accelerated the process of engraftment of huPBSC and spurred the spread of mature human cells to the murine spleen, liver, thymus, and peripheral blood. Cotransplants of allogeneic human bone marrow stromal cells derived from long-term cultures resulted in a comparable--though less prominent--support of engraftment.

Adult↗

[Large volume lymphocytapheresis for the collection of peripheral stem cells].

We performed 29 large-volume leukaphereses of 20 patients for collection of peripheral blood stem cells. All patients have been pretreated with cytokines after chemotherapy. In 9 patients with precounts of > or = 3 x 10(9) mononuclear cells/l we achieved a sufficient transplantation doses with one LVL. If the MNC precount was < or = 3 x 10(9)/l we had to perform more than one LVL. On 16 patients we compared a standard apheresis procedure with the LVL procedure. It seems that especially patients with a lower MNC precount can profit from LVL. From patients with higher MNC precounts we harvested the double amount of MNCs, from patients with lower MNC precounts the triple amount.

Female↗

[Stem cell pheresis and deep temperature preservation--a problem of transfusion medicine?].

In Germany, Transfusion Medicine belongs to various medical disciplines. We would like to demonstrate our model of interdisciplinary collaboration in stem cell transplantation. Since 1989 we performed 339 leukaphereses in 53 patients. On average we got 1.4 x 10(8) MNC/kg body weight from one single apheresis procedure. To observe graft quality we measured the content of CD34-positive cells and the amount of CFU-GM. Despite diagnosis and therapeutical regimen the content of CD34+ cells was found to be 3.3% (0-20). The proliferation was 21.7 GM-CFU per 1 x 10(5) MNC seeded (0-393). The results of the first 17 transplantations showed a fast haematological recovery (WBS 1.0 Gpt/l after 9 days Plt 20 Gpt/l after 11 days). Close collaboration of Transfusion Medicine and Haematology leads to optimization of stem cell transplantation.

Blood Transfusion↗

[Therapy results of acute leukemia 1965-1980].

At the instance of 174 patients with leukemia is demonstrated that the development to a more aggressive cytoreductive chemotherapy during the last 15 years achieved success without increasing the risk of treatment. A decisive improvement of prognosis for the acute leukemia of adult age is, however, to be expected only from new methods.

Acute Disease↗

[Prognostic significance of histobiopsy findings in bone marrow of malignant lymphomas in adults].

Issuing from the fact that the histobiopsy of the bone marrow is the most sufficient method for the proof of infiltrates of malignant lymphomas in the marrow, in 41 patients with Hodgkin's disease and 89 patients with malignant non-Hodgkin-lymphomas was tested whether already may be rendered prognostic conclusions from the histologic findings of the marrow. In these cases could be shown by the different course in patients with Hodgkin's disease in stage IV with and without affection of the marrow that a specific infiltration of the marrow is accompanied by a significant deterioration of the prognosis, which should be taken into consideration in the therapy planning. In the malignant non-Hodgkin-lymphomas those with a high degree of malignity showed a significantly worse prognosis than those with a low degree of malignity. Thus in the individual case the coordination of a lymphoma to one of these groups of malignity which is possible at the histobiopsy of the iliac crest may already be of prognostic significance also without consideration of the type of lymphoma. The prognostic significance of the type of lymphoma itself could be confirmed by the different course of the survival curves in the histologic subtypes of the immunocytoma. Since finally patients with a lymphoplasmocytic immunocytoma in diffuse affection of the marrow show a significantly worse prognosis than in the focal affection may be concluded that apart from the degree of malignity and the type of lymphoma also the type of affection of the marrow which is to be established histologically seems to have a decisive prognostic significance from which the necessity of a different therapeutic approach may be derived. Further examinations on larger numbers of patients including multivariant analyses will yield still more evident results.

Adult↗