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Biomedical subjects

G Ehninger

Publications and source records attributed to G Ehninger.

At least 217 records · Page 12Linked to original sources
PubMed1991

Pharmacokinetics and metabolism of cyclophosphamide administered after total body irradiation of bone marrow transplant recipients.

High-dose cyclophosphamide is used immediately after total body irradiation (TBI) in conditioning for bone marrow transplantation (BMT). Possible interactions of the two treatment modalities were sought by measuring the blood pharmacokinetics of CP and 4-hydroxy-cyclophosphamide (4-HOCP) in patients undergoing BMT. There was a non-significant trend to a shorter half-life of CP compared to reported values. Exposure to 4-HOCP, the major metabolite of CP, did not appear to be altered by prior TBI of the patient.

Adolescent↗
PubMed1991

Unaltered pharmacokinetics after the administration of high-dose etoposide without prior dilution.

The pharmacokinetics of etoposide following a new method of administration was determined. Undiluted etoposide was given at a dose of 30 mg/kg as part an intensified conditioning regimen prior to bone marrow transplantation. A terminal half-life of 3.4 +/- 0.7 h and a volume of distribution of 15.4 +/- 9.6 l were found (n = 8); the AUC was 764 +/- 302 micrograms h ml-1. As compared with those obtained in other pharmacokinetic studies using etoposide diluted in normal saline, our data reflect full systemic bioavailability and unaltered pharmacokinetics. The application of undiluted etoposide makes the therapy easier and less time-consuming and avoids a high fluid volume and a high saline load.

Acute Disease↗
PubMed1991

Clinical trial of natural human lymphocyte-derived interleukin 2 in cancer patients: effects on cytokine production and suppressor cell status.

Lymphocyte-derived, natural, glycosylated interleukin 2 (IL 2) may have different effects in vivo than the non-glycosylated recombinant IL 2 hitherto employed in clinical trials. To test this, 9 tumor patients were given 3-6 x 10(6) U/day natural IL 2 by continuous infusion for 5 days. Compared with previously published results obtained using recombinant IL 2, as far as similar tests were performed, no unexpected results were obtained with natural IL 2 in the present study. Plasma TNF-alpha levels increased considerably during therapy, IFN-gamma very slightly, whereas IL 2-stimulated secretion of either cytokine in vitro fluctuated greatly. CD16+ and CD25+ cells increased and CD45R+ cells decreased after treatment, consistent with significant lymphocyte activation in vivo. MHC-unrestricted cytotoxicity increased after treatment. The level of CD8+ cells was and remained within the normal range, although suppressive activity generated in mixed lymphocyte culture was deficient prior to therapy. Interestingly, this normalised after therapy. These results extend studies of immunological monitoring of patients receiving IL 2, based on the first trial using natural rather than recombinant IL 2.

Cytotoxicity, Immunologic↗
PubMed1991

The anti-fungal agent itraconazole exerts immunosuppressive effects on alloreactivity but not on natural immunity in vitro.

The anti-fungal azole drug itraconazole was compared with fluconazole regarding immunosuppressive effects in a model of human alloreactivity in vitro (the mixed lymphocyte culture, MLC) and in assays of non-adaptive immunity (natural killing, NK, and lymphokine activated killing, LAK). Itraconazole, but not fluconazole, strongly inhibited lymphocyte proliferation and the generation of allospecific cytolytic activity, but had no effect on the development of major histocompatibility complex (MHC)-unrestricted ("natural killer-like") cytotoxicity or of alloindifferent suppressive activity in MLC. Neither drug blocked LAK cell induction, nor the effector phase of either NK or LAK activity. These results suggest that itraconazole might represent a new class of immunosuppressive agent which specifically blocks alloreactivity without affecting natural immunity.

Antifungal Agents↗
PubMed1991

Comparison of the immunosuppressive activities of the antimycotic agents itraconazole, fluconazole, ketoconazole and miconazole on human T-cells.

Four antifungal agents have been screened in vitro for their immunosuppressive effects on proliferative responses in human mixed lymphocyte cultures (MLC). A hierarchy of inhibitory activity was observed, where itraconazole was greater than ketoconazole greater than miconazole greater than fluconazole, with itraconazole as suppressive as cyclosporin A, and fluconazole completely without suppressive activity. The mechanism of inhibition did not involve blockade of T-cell growth factor production and, consistent with this, interleukin-2-dependent T-cell clone proliferation was blocked by these agents in the same order of decreasing activity as in MLC. The secretion of cytokines without known T-cell growth factor activity (interferon-gamma, tumour necrosis factor-alpha) was also not significantly blocked by these agents. These results therefore demonstrate that antifungal azole drugs may be variably strongly immunosuppressive for human T-lymphocyte proliferation in vitro, but none appear to be so via a mechanism involving inhibition of cytokine secretion.

Antifungal Agents↗
PubMed1991

[Neurologic complications after bone marrow transplantation].

The retrospective study presented here reports clinical, electrophysiological and CT-data from 21 patients who underwent bone marrow transplantation for leukemia or aplastic anemia between 1980 and 1985. The aim of the investigation, which was performed at the end of 1986, was to elucidate whether antineoplastic drugs and radiation can result in long-term damage of the central nervous system. In 9 patients we observed neurological signs (1 leukencephalopathy, 5 cerebellar symptoms). Seven patients revealed dysrhythmia in the EEG and five had delayed latencies of visual evoked potentials. Eight patients exhibited pathological changes in CT (3 atrophy of supratentorial structures, 3 periventricular lucencies, 2 a combination of both). The results indicate that long-term damage to the CNS may be encountered after successful bone marrow transplantation.

Adolescent↗
PubMed1991

[Lung changes caused by Mycobacterium xenopi infection in a patient with bone marrow transplantation: problems in differential diagnosis].

Pulmonary affections caused by atypical mycobacteria are an increasingly common problem particularly in patients with immune deficiency disorders. We here report a case of pulmonary infiltrates due to Mycobacterium xenopi in a patient after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission and under immunosuppressive treatment with prednisolone and Cyclosporin A. While sputum cultures, serology as well as bronchial lavage and transbronchial biopsy remained inconclusive, diagnosis could only be established by open lung biopsy. We suggest that particularly in immunocompromised patients unclear pulmonary infiltrates require rapid and possibly invasive diagnostic procedures.

Adult↗
PubMed1991

Cytotoxic and proliferative functions of T lymphocyte clones derived very shortly after allogeneic bone marrow transplantation.

In a search for mechanisms of potential graft-versus-leukaemia (GVL) activity after allogeneic bone marrow transplantation (BMT), peripheral lymphocytes from five patients (four chronic myeloid leukaemia, one acute lymphoblastic leukaemia) 24-39 days post-transplant were precultured with pretransplant host leukaemia cells and then cloned by limiting dilution with interleukin-2 (IL-2). Clones obtained were exclusively CD3+ CD56-, carried the alpha/beta form of the T cell receptor for antigen, and were mostly (88% of 138) CD4+. None of 143 clones, including CD8+ clones, convincingly lysed host pretransplant cells, although 35 (24.5%) manifested lytic potential in lectin-mediated cytotoxicity assays. Measuring the proliferative responses of 118 of these clones in the presence of exogenous IL-2 revealed that a small number of clones reacted more strongly to host leukaemia than to unrelated leukaemias or B lymphoblastoid cell lines. In the two cases tested, the donor's untransplanted lymphocytes cloned under the same conditions as post-transplant cells did not generate any clones reacting preferentially with host leukaemia cells. These results may suggest that some T cells appearing shortly after allogeneic BMT could potentially mediate anti-leukaemia activity not associated with cytolysis of target cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Toxicity of novel anthracycline derivatives towards normal myeloid bone marrow progenitor cells (CFU-GM) is not increased by verapamil.

Drug-induced myelotoxicity is usually the dose-limiting factor of treatment of malignant tumors with cytostatic drugs. Suppression of in vitro myelopoiesis (CFU-GM) by cytostatics may be a suitable model reflecting the in vivo situation. Thus the inhibitory effects of the anthracyclines doxorubicin, theprubicin, idarubicin and cytorhodin S on CFU-GM were compared. Normal human bone marrow cells were incubated with these drugs for one hour and alternatively, for the whole culture period. For each substance and each incubation time a dose-response curve was established and the D50 determined. As certain calcium antagonists can increase the toxicity of some cytostatic drugs in various tumor models, the effect of the addition of verapamil (2 microM) was also investigated. It could be shown, that the myelotoxicity on CFU-GM of the drugs mentioned above was not increased after short-term or permanent exposure to this calcium antagonist.

Antibiotics, Antineoplastic↗
PubMed1990

Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-alpha-treated chronic myelogenous leukaemia patients.

Chronic myelogenous leukemia (CML) patients in chronic phase display compromised lymphokine-activated killer (LAK) cell induction, which is partly restored after therapy with interferon alpha. However, the relative resistance of the leukemic cells from these patients to autologous or allogeneic LAK lysis is not affected by this treatment. In an attempt to render CML cells more susceptible to lysis or cytostasis, they were precultured in serum-free medium with or without recombinant growth factors. In eight patients studied, interleukin-3 (IL-3) significantly enhanced the spontaneous short-term (6-day) proliferation of CML cells, with retention of ability to form colonies in methylcellulose. Culture in either medium alone or IL-3 led to a significant enrichment of CD14+ and CD33+ cells but to a reduction in CD34+ cells. In contrast, culture of the same cells in IL-2 (to generate autologous LAK activity) resulted in a loss of CD14+ and CD33+ as well as CD34+ cells but in a significant increase in CD3+ and CD56+ cells. Despite similarities in their phenotypes, IL-3 cultured cells but not those cultured in medium alone acquired susceptibility to lysis by the IL-2-cultured autologous LAK cells. These results may have significance for the design of novel combination immunotherapy in CML.

Antigens, Surface↗
PubMed1990

TBI technique and clinical results of leukemia patients at the University of Tübingen.

Since 1976, more than 180 patients suffering from leukemia or aplastic anemia have been treated with BMT and TBI. The improvement of TBI-technique starting from single fraction irradiation without any shielding to different types of fractionation schemes with lung, head and neck shielding and an electron boost to the thoracal wall is shown. A more detailed description of the actual TBI-technique is given; this has been applied to 64 patients to-date. Some clinical results are summarised into four subgroups. Life table analyses are shown for single fraction irradiation as well as for fractionated irradiation separated for high and for low risk patient groups.

Anemia, Aplastic↗