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Biomedical subjects

D Niethammer

Publications and source records attributed to D Niethammer.

At least 199 records · Page 11Linked to original sources
PubMed1988

Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation.

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.

Acute Disease↗
PubMed1988

Prevention of CMV infection after BMT in high-risk patients using CMV hyperimmune globulin.

Prophylactic administration of an intravenous cytomegalovirus hyperimmune globulin in bone marrow transplant recipients provided protection against primary as well as reactivated CMV infection in patients considered to be at high risk for cytomegalovirus infections. Forty-one patients were divided in six subgroups according to factors considered to increase the incidence and severity of CMV infections following bone marrow transplantation. All of these patients received blood products from donors not screened for active or latent CMV infections. In spite of this, patients undergoing intensified conditioning therapy or mismatch transplantation, as well as those transplanted in relapse of their leukemia and even patients receiving granulocyte transfusions from donors unscreened for CMV serostatus, were found not to develop primary or secondary CMV infections. Only in the group of patients older than 35 years and among those suffering from severe GVHD six patients were found to have CMV infections, only two a symptomatic form. Intravenous administration of CMV hyperimmune globulin effectively protected even patients at high risk for CMV infection against severe complications of primary infection or reactivation of this virus.

Adult↗
PubMed1988

Significant reduction of cytomegalovirus (CMV) disease by prophylaxis with CMV hyperimmune globulin plus oral acyclovir.

The effect of prophylactic intravenous administration of a cytomegalovirus (CMV) hyperimmune globulin with a high titer of neutralizing antibodies plus oral acyclovir was studied in 93 consecutive bone marrow transplant recipients. In spite of receiving blood products unscreened for CMV only six patients developed CMV infections during the time they received passive immunization. Five patients reactivated virus after hyperimmune globulin infusions were stopped; four of them suffered from chronic graft-versus-host disease (GVHD) Among the patients suffering from acute GVHD grade III/IV and/or chronic GVHD the incidence of CMV infection (10/38) was significantly higher than among those with no or milder forms of GVHD (1/55) (p less than 0.01). Only three patients suffered from symptomatic CMV infections; two with gastrointestinal manifestations and one with fatal CMV pneumonia. Thus CMV prophylaxis as used here proved highly effective in combating one of the major difficulties encountered in BMT.

Acyclovir↗
PubMed1988

MIBG-treatment in neuroblastoma; experiences of the Tübingen/Frankfurt group.

27 children with neuroblastoma were treated with 131I-Metaiodobenzylguanidine (MBIG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were evaluable for analysis of results. In 4 children (16.7%) a CR was observed, in 10 (41.7%) a PR, in 5 (20.8%) a disease stabilization and 5 were nonresponders. The 4 CR-patients were initially stage IV. 3 of them were treated in addition by bone marrow transplantation (bmt), one by further chemotherapy. 3 died of a relapse, 1 of complications from bmt. 5 of the 10 PR-patients died of tumor progression, 3 achieved a CR by additional chemotherapy, 1 a PR by bmt and 1 stays in PR without further measures. 2 of the 5 children with a disease stabilization were the first treated patients to whom a fairly low dose was given. In 3 of the 5 nonresponders no uptake of MIBG was observed; they died from tumor progression. 1 of the 2 nonresponders with uptake died of graft-versus-host disease after bmt, 1 other also of tumor progression. Duration of remission was between 1 and 12 months and depended upon uptake and dose of MIBG, interval between administrations and individual tumor behaviour. Side effects were seen as marked bone marrow depression; this was reversible in any case and we did not loose a patient due to MIBG-induced leuko- or thrombopenia. In cases of severely ill children we observed a very fast and dramatical amelioration in clinical conditions. With this method even in neuroblastoma relapse and in nonresponders complete remissions are achievable. Important is the intensification of the therapeutical effect by additional chemotherapy or in combination with bmt. For a definitive evaluation further investigations are necessary to optimize therapeutic strategies.

3-Iodobenzylguanidine↗
PubMed1987

Characterization of actinomycin-D-resistant CHO cell lines exhibiting a multidrug-resistance phenotype and amplified DNA sequences.

Actinomycin D (DACT)-resistant sublines of the Chinese hamster ovary cell line CHO-K1 were selected in vitro. Sublines were derived which expressed 5.2-fold (CHO 15DACT) and 35.8-fold (CHO 100DACT) resistance to DACT. The CHO 100DACT subline displayed marked cross-resistance to bleomycin, adriamycin, daunomycin, vinblastine, vincristine, VP 16 and VM 26. No cross-resistance was found to cisplatin or methotrexate. The resistant cells exhibited enhanced (collateral) sensitivity to prednisolone. Combination of prednisolone with vincristine resulted in a pronounced synergistic effect on sensitive cells, whereas in resistant cells the combined effect of both drugs was merely additive. Resistant cells, viably stained with the DNA-specific dye Hoechst 33342, exhibited decreased fluorescence intensities compared to parental cells. In contrast to sensitive cells the resistant sublines did not accumulate the mitochondria-specific dye rhodamine 123. Co-incubation with verapamil, however, effectively enhanced accumulation of the dye. The potential diagnostic value of these fluorescent compounds as marker dyes for the multidrug-resistance phenotype is discussed. Non-toxic doses of verapamil almost completely reversed the resistance to various drugs in CHO 100DACT cells. Specific DNA sequences were amplified in resistant cells, and the increase in resistance was paralleled by a concomitant increase in the copy number of these sequences, suggesting that the corresponding gene may be functionally linked to the multidrug-resistance phenotype.

Animals↗
PubMed1987

[Functions of intrinsic defense against anaerobic bacteria in healthy probands and patients with chronic-septic granulomatosis].

Different strains of Bacteroides fragilis exhibit great differences in sensitivity towards serum from healthy volunteers. In the presence of 10% autologous serum, neutrophilic granulocytes and monocytes (macrophages) caused significant killing of B. fragilis. The measured phagocytic and killing activity of the cells is comparable to their activity against aerobic bacteria (S. aureus). In four patients with chronic granulomatous disease of childhood, phagocytosis was normal but killing of B. fragilis and S. aureus in granulocytes or monocytes (macrophages) was appreciably lowered. This malfunction of the cells was accompanied by a disturbance in oxidative metabolism and inadequate iodination after phagocytosis of B. fragilis. The results suggest that granulocytes and monocytes play an important role in host defense against endogenous infections with anaerobes.

Abscess↗
PubMed1987

Treatment of neuroblastoma with metaiodobenzylguanidine: results and side effects.

Between April 1984 and December 1985 we treated ten children suffering from neuroblastoma in a total of 25 metaiodobenzylguanidine (MIBG) courses. Five had had a relapse of neuroblastoma stage III or IV, three had never achieved a remission in spite of intensive chemotherapy, and two were treated with an unstable remission. The children were each administered from 1 to 5 courses with a dosage per course of between 1,295 and 9,065 MBq. The sum of the single doses during the whole course of therapy ranged between 3,145 and 21,904 MBq per child. Five of five children suffering from bone pain and fever became free of complaints during the first three treatment days. Six of eight children with manifest tumor at onset of therapy responded well to the treatment: response extended from transitory decrease in elevated catecholamine levels in serum and urine to complete disappearance of large abdominal tumor masses. We also observed a decrease in bone marrow involvement and a stabilization of osteolytic lesions. Seven of these eight children died in spite of a good response from 55 to 350 days after the first MIBG treatment course. The only side effect we witnessed was a reversible bone marrow depression. In three children we combined the MIBG therapy with bone marrow transplantation.

3-Iodobenzylguanidine↗
PubMed1987

High-dose methotrexate therapy with leucovorin rescue: in vitro investigations on human osteosarcoma cell lines.

High-dose methotrexate (MTX) therapy with subsequent leucovorin (LV) rescue (HDMTX-LV) in the treatment of osteosarcoma is based on the assumption that this tumor has a deficient uptake system for MTX and reduced folates. To simulate features of HDMTX-LV therapy protocols in vitro, sensitive and MTX-resistant human osteosarcoma cell lines and a lymphoblastoid cell line were exposed to MTX and/or LV at various dosages and time schedules and the effects on DNA metabolism and on cell growth were evaluated. The data show that in osteosarcoma cells and in lymphoblasts the cytotoxic effects of 10(-6) M to 10(-7) M MTX can be substantially reversed by LV if the antidote is applied within the first 12 h of MTX exposure. The results are not consistent with the assumption mentioned above and should be taken into consideration when designing new therapeutic regimens. An alternative hypothesis for the efficacy of HDMTX-LV is discussed. It is concluded that HDMTX-LV therapy may be effective in the treatment of osteosarcoma, even when subpopulations of the tumor cells exhibit different mechanisms of resistance to MTX, such as elevated levels of dihydrofolate reductase or a deficient transport system for MTX, if high doses of MTX are applied long enough to ensure lethal intracellular MTX levels and low-dose LV schedules instituted after a long delay are used.

Cell Line↗
PubMed1987

Successful bone marrow transplantation from an unrelated donor in a child with AML in second remission.

In February 1986 we transplanted a 10-year-old girl with AML in second remission with the bone marrow of an unrelated donor. HLA-types were different for one A- and one B-antigen between patient and donor. Conditioning regimen consisted of 14 Gy total body irradiation with lung shielding, 8 X 3 g/m2 cytosin arabinoside and 90 mg/kg cyclophosphamide. GVHD-prophylaxis was performed with cyclosporin A, methotrexate and prednisolone. Only mild GVHD I of the skin could be observed after rapid engraftment. 100 days after transplantation the patient was in good clinical condition and GVHD-prophylaxis was discontinued without any reactivation of acute or chronic GVHD. Engraftment was documented by sex chromosome and blood group typing. 120 days after transplantation leukemic blasts were detected in the peripheral blood and the child died 130 days after BMT from relapse of the leukemia. Despite the negative outcome, this was the first successful bone marrow transplantation from a unrelated donor in Germany.

Bone Marrow Transplantation↗
PubMed1987

[Disorders of hematopoiesis in immunodeficiencies].

There is increasing experimental evidence for the influence of the immune system on the regulation of hematopoiesis. The question is how much information on the basic pathomechanisms we can gain when we study the disturbances of hematopoiesis observed in congenital and secondary immunodeficiencies. Frequently, there is a contradiction between in vitro results and in vivo observations. Only in some cases (e.g. the development of eosinophils), are experimental results supported by clinical observations. All concepts of regulation and influence of the immune system on hematopoiesis have to be measured against the disturbances seen in the patients.

Hematopoiesis↗
PubMed1987

Methods for the determination of the interferon-induced enzyme 2'-5' oligoadenylate synthetase in mononuclear blood cells.

The determination of 2'-5'-oligoadenylate synthetase in peripheral blood mononuclear cells is used as a biological response parameter during therapy with interferon and in the diagnosis of diseases related to the interferon system. In this communication, some general aspects concerning the preparation of 2'-5'-oligoadenylate synthetase from peripheral blood mononuclear cells and the incubation conditions of the 2'-5'-oligoadenylate synthetase reaction are reported. Four analytical procedures for the determination of the products formed during the 2'-5'-oligoadenylate synthetase reaction were comparatively investigated and the advantages and limitations of the assays are discussed. As an example of possible clinical application, the levels of 2'-5'-oligoadenylate synthetase were determined in the mononuclear cell fraction of peripheral blood from healthy persons as well as from children with chronic myelogenous leukaemia.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Kinetics of restoration of interferon production after bone marrow transplantation in man.

Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Lung diseases after bone marrow transplantation. Results of a clinical, radiological, histological, immunological and lung function study.

The case histories of 72 subsequently treated patients - 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma - were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterial-mycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/microliter correlated significantly (P less than 0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P less than 0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P less than 0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P less than 0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.

Adolescent↗