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Biomedical subjects

D Niethammer

Publications and source records attributed to D Niethammer.

At least 217 records · Page 12Linked to original sources

Acute folic acid deficiency after bone marrow transplantation.

After bone marrow transplantation (BMT), megaloblastic bone marrow changes are often observed that can only be partially explained by drug effects. Our goal was to find out whether folic acid deficiency represented an additional factor. The serum folic acid concentrations of 41 patients were determined regularly before and after BMT. A 2nd degree polynomial regression analysis revealed a clear and acute drop in folic acid concentrations within 7-9 days after BMT. In 19 patients the level fell below 3.0 ng/ml, the range of folic acid deficiency. The mean folic acid values without oral administration of folic acid after BMT lay significantly below the mean values with substitution (P less than 0.001). If a case of acute graft versus host disease (GvHD) was more severe than grade I, the mean folic acid levels were significantly lower (P less than 0.01). Patients with megaloblastic bone marrow changes after BMT had significantly lower folic acid values than those without such changes (P less than 0.01). The 18 patients with folic acid deficiency had a significantly higher rate of megaloblasts, binucleate erythropoietic precursors, Howell-Jolly bodies, giant myelocytes, and giant metamyelocytes in bone marrow smears than the remaining 23 patients (P less than 0.05). Folic acid deficiency did not slow down the increase in leukocytes, granulocytes, thrombocytes, or reticulocytes after BMT. There were 8.2%-9.7% hypersegmented neutrophils in the blood (normal 5%) after BMT both with and without folic acid deficiency. Folic acid deficiency after BMT was caused by insufficient intake combined with simultaneous decreased intestinal resorption and increased requirements for the regeneration of bone marrow and intestinal mucosa.

Adolescent↗

Appearance of an inherited porphyria cutanea tarda in a child after allogeneic bone marrow transplantation for chronic myelogenous leukaemia.

We report details of a 6 1/2-year-old girl who developed porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. The results of studying porphyrin metabolism in the family members are described. Expression of the disease may have been induced by the cyclophosphamide and total-body irradiation in the conditioning regimen and/or by the administration of methotrexate for the prevention of graft-versus-host disease and meningeal leukaemia.

Bone Marrow Transplantation↗

The role of reactive oxygen compounds derived from 6-hydroxydopamine for bone marrow purging from neuroblastoma cells.

6-Hydroxydopamine(6-OHDA), a specific neurotoxin against sympathetic nerve cells, is a drug already used for purging of bone marrow from neuroblastoma cells before autologous bone marrow transplantation. However, we could not detect significant differences in the toxicity of 6-OHDA against neuroblastoma and other tumor cells under the purging conditions clinically used. In contrast, bone marrow stem cells were much more resistant. The unspecific toxic effect of 6-OHDA is caused by H2O2 or H2O2-derived products which are generated by auto-oxidation in the incubation medium before a significant amount of 6-OHDA is taken up by the cells. Withdrawal of oxygen during the incubation period and subsequent incubation with an oxygen containing medium led to a more specific destruction of neuroblastoma cells which can take up 6-OHDA selectively.

Ascorbic Acid↗

The combined effect of interferon-beta and cytostatic drugs on human tumor cell lines in vitro.

Three human tumor cell lines (one osteosarcoma and two neuroblastoma lines) were assessed for combined interferon-beta (IFN-beta)/chemotherapeutic drug antigrowth effect under in vitro conditions. Two different methods to measure this effect were used: colony formation in soft agar and counting of cells growing as monolayers. The cells were incubated with a chemotherapeutic drug (adriamycin, dacarbazine, actinomycin D, cis-platinum, methotrexate, VP-16-213, or vincristine) at relevant concentrations for 1 h, washed twice, and incubated with IFN-beta in concentrations ranging from 100 to 1000 IU for continuous exposure. All combinations resulted in an additive or synergistic combination effect with one exception: methotrexate/IFN-beta in the monolayer method after 1 week, a combination which was additive after 3 weeks however. The combinations VP-16-213/IFN-beta and cis-platinum/IFN-beta produced the most pronounced synergistic effects. A statistical evaluation of the null hypothesis for additivity was done. These results provide a rationale for designing clinical studies combining IFN-beta with current chemotherapeutic drugs.

Antineoplastic Agents↗

Recombinant interferon-alpha-2C in laryngeal papillomatosis: preliminary results of a prospective multicentre trial.

A preparation of interferon-alpha 2C of high purity formed by recombinant DNA technology was used as adjuvant therapy following removal of laryngeal papillomas by cauterization or laser vaporization. Preliminary data on 20 patients are reported and include 11 complete and 7 partial responses. Side-effects included initial temperature elevation, but this subsided and other side-effects were uncommon. No antibodies to the interferon preparation were found in any of the patients.

Clinical Trials as Topic↗

Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH.

The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific uptake could be demonstrated for the other neuroblastoma lines, as well as for an osteogenic sarcoma line (SAOS-2) and a melanoma line (IgR 3). Based on analyses of uptake characteristics from Lineweaver-Burk plots it is evident that two different transport mechanisms are responsible for mIBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4 degrees compared to 37 degrees, as well as in the presence of ouabain or the absence of oxygen. A competitive inhibition of the transport of mIBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of mIBG was still retained in the SK-N-SH cells 24 h after the end of incubation with mIBG, whereas no mIBG was detectable in SK-N-LO cells already after 1 h.

3-Iodobenzylguanidine↗

Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.

One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event-free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.

Adolescent↗

Bone marrow transplantation for acute leukemia in second or subsequent remission.

Twenty-one patients with acute leukemia in second to fifth remission were treated with bone marrow transplantation: 19 patients with transplants from HLA-matched siblings and two with transplants from identical twins. Twelve patients survived from 15 to 1,625 days after transplantation: six of 11 in the ALL group and six of 10 in the AML group. Recurrence of leukemia after marrow transplantation occurred in five patients. The cause of death in five patients was infection, in two patients combined with graft-versus-host disease. Long-term disease-free survival can probably be achieved in 30%-35% of all patients with acute leukemia who receive a marrow transplant in second or subsequent remission.

Adolescent↗

IgG therapy in systemic lupus erythematosus--two case reports.

Two paediatric patients with systemic lupus erythematosus were treated with immunoglobulin G (IgG). In the first case treatment resulted in regression of the most acute symptoms and a long remission was achieved. In the second patient, who was treated during the chronic stage of the disease, there was no significant effect on the course of the SLE.

Azathioprine↗

In vivo effects of interleukin 2 on lymphocyte subpopulations in a patient with a combined immunodeficiency.

This report describes a clinical trial with Interleukin 2 (IL-2) on a 17-month old male child with combined immunodeficiency (Nezelof's syndrome). IL-2 was prepared from conditioned media of phytohemagglutinin-stimulated leukocytes from buffy coats. The purification of IL-2 involved chromatography on Matrex Blue A sepharose and gel filtration chromatography. The preparation was free of macrophage cytotoxicity factor, macrophage migration inhibition factor and colony-stimulating factor. It contained negligible activity of interferon-gamma. IL-2 activity was adjusted to 1600 U/ml, which corresponds to about 0.8 micrograms homogeneous IL-2/ml. The patient was treated over a 50-day period with a total dose of 20,000 U IL-2, which was injected subcutaneously. IL-2 was well tolerated. Within 3 weeks, the treatment led to a normalization of a lymphocytosis which had prevailed for the previous 3 months. A pronounced eosinophilia also improved but did not reach normal levels. The most striking effect was a normalization of the OKT4+/OKT8+ ratio with a concomitant relative increase in OKT3+ cells in the peripheral blood. No effects were seen on E rosette formation, B cell counts or serum Ig levels. Also NK or ADCC activity remained high, as before the treatment. Infectious episodes and requirement for antibiotic treatment were less frequent during IL-2 therapy. Some effects of IL-2 were transient, e.g., the counts of OKT4+ and OKT3+ cells which returned to pathological values a few weeks after the treatment was discontinued.

Humans↗

[Psychosocial consequences of cancer in a child for its parents and siblings].

Cancer in children leads to extreme situations not only for the child but for all members of the family. Fear of death quite often over years has severe psychosocial consequences for the sick child, its parents and siblings. Without sufficient help from the therapeutic team the family is usually not able, to cope with these problems.

Adolescent↗