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Biomedical subjects

G Ehninger

Publications and source records attributed to G Ehninger.

At least 253 records · Page 14Linked to original sources
PubMed1989

Absence of significant interaction of fluconazole with cyclosporin.

The effect of a new azole antifungal drug, fluconazole, on cyclosporin concentration and pharmacokinetics was studied in ten bone marrow transplant recipients. There were no significant statistical or clinical differences in mean cyclosporin trough concentrations, peak concentrations and AUCs after fluconazole given either as a single 100 mg oral dose or as 100 mg daily for 14 days. Fluconazole was well tolerated without drug related side effects. Slight to moderate increases of liver laboratory parameters were observed in four patients during the multiple dose sequence, but these changes might be attributable, in part, to the underlying diseases or concomitant therapies. The data suggest a lack of clinically relevant pharmacokinetic interaction of fluconazole with cyclosporin. It is concluded that fluconazole may be administered to cyclosporin treated patients without enhanced risk of toxicity.

Adult↗
PubMed1989

Decreased essential antioxidants and increased lipid hydroperoxides following high-dose radiochemotherapy.

The blood from 19 patients having bone marrow transplantation was examined for the essential antioxidants alpha-tocopherol and beta-carotene as well as lipid hydroperoxides before, at and after bone marrow transplantation (BMT). Conditioning therapy, preceding BMT in order to achieve marrow ablation and immunosuppression, consists of high-dose chemotherapy which is mostly combined with total body irradiation (TBI). In order to see a possible difference between patients with and without additional TBI, we divided the patients up into two groups; patients receiving TBI (RT+) and patients without TBI (RT-). All patients required total parenteral nutrition beginning one week prior to BMT. After conditioning therapy plasma levels of absolute and lipid-standardized alpha-tocopherol and beta-carotene decreased in both groups, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early post-transplant toxicity. Lipid hydroperoxides increase significantly in the group of patients with additional TBI, whereas the other group, receiving no additional TBI, showed no significant change. We suggest high-dose supplementation of essential antioxidants for patients undergoing BMT.

Adolescent↗
PubMed1989

Bone marrow transplantation in childhood leukaemia--experience and strategies in the Federal Republic of Germany.

BMT has gained its place in the treatment of childhood leukaemia. Nevertheless, there are still many questions open. In acute lymphoblastic leukaemia children should normally be grafted in 2nd remission (CR). Some high risk cases, however, should probably be grafted in 1st CR. It is not clear whether children with late relapses benefit more from BMT than from renewed chemotherapy. Children with a relapse during maintenance therapy, however, have a better survival rate with BMT. In acute nonlymphoblastic leukaemia certain high risk patients should be grafted in 1st CR but it has still to be shown that BMT is superior to chemotherapy in such cases. It is not clear whether children with a relapse following intensive chemotherapy (such as the BFM-protocols) will benefit from BMT at all. In chronic myelocytic leukaemia, BMT in chronic phase should be performed. Thus, for the first time cure has become possible for this disease. Waiting for acceleration or even the occurrence of a blast crisis decreases the chance of survival after BMT dramatically. Since complications of BMT such as graft-versus-host reaction or severe infections are less frequent in children, relapses remain the main problem after BMT in childhood leukaemia.

Bone Marrow Transplantation↗
PubMed1989

Bone marrow transplantation in children with neuroblastoma.

Neuroblastoma is the third most frequent malignant tumor in childhood. One-third of the patients over one year of age at the time of diagnosis suffer from the disseminated form (stage IV). Despite highly aggressive chemotherapy survival rates are poor. One hundred and eighty-seven patients with neuroblastoma stage IV have been treated according to the German protocol NB 85. The probability of disease free survival is only 15% after 70 months. Treatment strategy in our protocol includes autologous and allogeneic bone marrow transplantation (BMT) for patients with stage IV (and greater than 1 year old). Twenty-two patients were grafted (7 allogeneic and 15 autologous). The conditioning regimen consisted mainly of high-dose melphalan (180 mg/m2) and total body irradiation (TBI) (3.4 Gy). Survival rates are discussed in the context of the chemotherapy protocol. Our own experience with autologous BMT is poor, despite of different purging methods. For this reason we decided to focus on allogeneic BMT. We have grafted five patients within the last 3 years. Three of them are alive and well, on died from veno-occlusive disease 70 days after BMT, and the remaining patient, grafted from a syngeneic donor, died from relapsing tumor. The main problem in neuroblastoma stage IV is resistance to chemotherapy. Intensification of the conditioning regimen or double autografting leads to a rate of toxic deaths close to 20% (Zucker, EBMT 1987) which is not tolerable. New improvements in the conditioning regimen have to be found to increase the effect of BMT.

Bone Marrow Transplantation↗
PubMed1989

Influence of allogeneic bone marrow transplantation on the endocrine system in children.

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.

Anemia, Aplastic↗
PubMed1989

[International bone marrow donor exchange].

More than 200 bone marrow transplants utilizing unrelated donors were done worldwide. In patients with chronic myelogenous leukemia survival rates up to 50% were published. Due to the low number of HLA-A, -B, -DR-typed donors in Europe donor search will be successful in only 13% of patients. Efforts should be directed to make an international donor search easier and to increase the donor pool size in each country.

Bone Marrow Transplantation↗
PubMed1989

Isolated pericardial relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia.

A 34-year-old male patient developed an isolated pericardial relapse of an acute myelogenous leukemia (M3) 11 months after marrow grafting from his HLA-identical brother. Alloenzyme pattern analysis revealed recipient type of the myeloblasts obtained from the pericardial effusion. Recurrence of the original leukemia was preceded by a reactivation of latent cytomegalovirus (CMV) infection which, in spite of a systemic humoral immune response to the virus, persisted in the pericardium as shown by dot-blot hybridization using CMV-specific DNA fragments. Activated T cells propagated with IL-2 from the pericardial effusion did not reveal any cytotoxic or restimulation capacity on the original or relapse myeloblasts, nor on other donor, recipient or NK target cells. Local coincidence of virus persistence and leukemic relapse suggested CMV-mediated modulation of the immune response in the pericardium with consequent induction of a proliferation of the original malignant cell clone. After local chemotherapy and one course of systemic treatment the patient is still in complete remission--longer than after the marrow grafting.

Adult↗
PubMed1989

5-Lipoxygenase inhibition by antifungal azole derivatives: new tools for immunosuppression?

The effect of novel azole derivatives (itraconazole and fluconazole) on 5-lipoxygenase activity was examined using human polymorphonuclear leukocytes (PMNL) as the enzyme source. The novel imidazole derivative itraconazole proved to be a potent inhibitor (IC50 2 X 10(-6) M) of 5-lipoxygenase activity. In contrast, fluconazole, an antifungal agent with bistriazole structure, had no effect on the Ca2+ ionophore A 23187-induced formation of 5-lipoxygenase metabolites in PMNL.

Antifungal Agents↗
PubMed1989

The isolation and identification of indigo and indirubin from urine of a patient with leukemia.

The urine of a patient who suffered from acute myelomonocytic leukemia was red coloured after administration of mitoxantrone and etoposid. The isolation and spectroscopic identification of the excreted pigments resulted in the chemical structures of indigo and indirubin. The structure elucidation has been carried out by taking use of a two-dimensional technique in high-resolution nuclear magnetic resonance spectroscopy and different mass spectrometric methods, including tandem mass spectrometry. Possible reasons for the formation of the indigoid compounds are discussed.

Antibiotics, Antineoplastic↗
PubMed1988

Human leukocyte antigen-DP in leukemia.

Human leukocyte antigen-DP (HLA-DP) typing was performed on patients with chronic myelogenous leukemia (CML, n = 44), acute nonlymphoblastic leukemia (ANLL, n = 34), or acute lymphoblastic leukemia (ALL, n = 41). Frequencies of DPw alleles in CML and ANLL patients were not significantly different from 254 controls, except that in ANNL DPw1 was absent. This was most likely due to the concurrent absence of DR3 with which DPw1 is in linkage. In contrast, in ALL, frequencies of DPw2 and DPw5 were significantly increased (corrected P less than 0.05, relative risk (RR) = 2.19 and corrected P less than 0.01, RR = 6.92, respectively). This was not due to linkage with DR. The frequency of DPw1 also tended to be reduced, but this was not caused by a similar decrease of DR3 in ALL. These results, therefore, demonstrate both positive and negative associations between major histocompatibility complex (MHC) gene products which are in only very weak linkage with the rest of HLA, and acute lymphocytic, but neither acute nor chronic myelogenous, leukemias. The HLA-DP region could thus contain long sought-after genes influencing susceptibility and resistance to leukemogenesis.

Alleles↗