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Biomedical subjects

D Schuler

Publications and source records attributed to D Schuler.

At least 73 records · Page 4Linked to original sources
PubMed1988

Methotrexate administered by 6-h and 24-h infusion: a pharmacokinetic comparison.

The pharmacokinetics of 8 g/m2 methotrexate (MTX) was compared following short (6 h) and long (24 h) infusions of the drug to 11 children with osteogenic sarcoma (OS; 42 infusion) and 28 children with acute lymphoblastic leukemia (ALL: 118 infusions), respectively. No difference was observed in the first-phase half-life, in systemic clearance or in the volume of distribution of the drug (P greater than 0.05). The concentration of MTX at the end of the infusion was approximately 4-fold higher when the drug was given over only 6 h. However, patients receiving 24-h infusions had approximately 9-fold higher levels by 24 h after the beginning of the infusion. The area under the data curve from start of the MTX infusion until the beginning of folinic acid rescue administration was significantly higher in patients with osteogenic sarcoma (6-h infusions), while the area under the log-data curve was significantly longer in the ALL group (24-h infusions) for the same period. The latter parameter is considered to be characteristic for the concentration-time-effect relationship. The longer duration of MTX administration (with delayed rescue) is thought to be more beneficial from the pharmacokinetic aspect. Patients with osteogenic sarcoma had significantly lower concentrations of MTX at the end of their last treatment with MTX than at the end of the first infusion. Patients developing MTX toxicity had shorter half-lives of MTX in the beta phase. It is suggested that cisplatin induced tubular loss of MTX and folinic acid is responsible for these observations. A wider application of clinical pharmacologic findings in the practice of the administration of cytostatics is indicated.

Child↗
PubMed1988

Cytogenetic investigations on children with acute non-lymphocytic leukemia.

Cytogenetic data from 30 children with acute non-lymphocytic leukemia (ANLL) are evaluated in connection with patient's age, morphological type of leukemia and prognosis. In 20 out of 30 patients clonal chromosome aberrations were found. The frequency of chromosome aberrations and the prognostic parameters in the various morphological and age groups proved to be different and no direct relationship could be found in a given group between the frequency of aberrations and the prognosis. A more detailed analysis of data, however, provided some evidence that chromosome aberrations observed at diagnosis had a prognostic value independent of age and the morphological properties of blast cells: the normal karyotype and the pseudodiploidy proved to be of a favorable value but the hyperdiploidy and polyploidy an unfavorable prognostic parameter. Besides the known cytogenetic differences between childhood and adult ANLL, some similarities are also emphasized.

Acute Disease↗
PubMed1988

Dibromdulcitol containing chemotherapeutic regimen in the treatment of childhood Hodgkin's disease.

Dibromdulcitol containing modified MOPP chemotherapeutic regimen plus radiotherapy were used in 58 children with Stage I-IV Hodgkin's disease diagnosed between 1975 and 1985 in Hungary. A remission rate of 93.1% and a 5-year relapse-free survival of 89% was observed. Some latent hyperthyreoidism as late effect of the therapy, no growth disturbances and no adverse gonadal effects were seen until now.

Adolescent↗
PubMed1987

Prognostic importance of systemic clearance of methotrexate in childhood acute lymphoblastic leukemia.

Pharmacokinetic studies of methotrexate have been carried out in 21 children with acute lymphoblastic leukemia diagnosed in 1981. Children were treated with intermediate dose (500 mg/m2) methotrexate in keeping with the 1981 ALL treatment Protocol of the Hungarian Childhood Leukemia Working Group. Of the 21 children, 8 relapsed, and 13 are in continuous complete remission. In the relapsed patients significantly increased systemic clearance of methotrexate was observed at the time of the second methotrexate treatment cycle compared with the calculated value after the first administration of the drug. No such change in the clearance was found in patients who are still in remission. There was no difference between children who relapsed or who are in remission in the elimination half-time of the drug. Age, sex, WBC at diagnosis, and systemic clearance of methotrexate were found to be connected with the probability of relapse in the patients studied. The possible reasons for the prognostic role of systemic methotrexate clearance are discussed.

Child↗
PubMed1987

Childhood rhabdomyosarcoma in Hungary.

56 children with rhabdomyosarcoma were treated in Hungary between 1975 and 1984. Tumor localization, age and sex distribution was similar to reported figures. Survival analysis demonstrated a better prognosis for orbital and urogenital rhabdomyosarcoma. Except for Stage I patients the more advanced cases had an inferior survival to other reported series. Intensification of therapy did not seem to clarify this point. Improving survival necessitates a uniform therapeutic approach that takes prognostic factors into consideration.

Child↗
PubMed1986

Aclacinomycin-A in the induction treatment of childhood AML.

In the cooperative study AML-IGCI-84 27 children with AML (FAB M1 7X, M2 4X, M3 1X, M4 6X and M5 8X; 1 megakaryocytic leukemia) have been treated. The median initial white blood cell count was 18.0 G/l (range 1.8-1,350.0 G/l). 1 or 2 courses of induction therapy were used: I1 (aclacinomycin-A (ACLA-A), VP-16 and ARA-C) and I2 (daunorubicin (DNR), VP-16, and ARA-C). I2 was used only if bone marrow contained greater than 5% blast cells on day 21. I2 and consolidation treatment were identical with the current AML-BFM-83 protocol. 3 deaths before day 21 occurred (2 cerebral hemorrhages, 1 septicemia). 24 patients were evaluable for response, 20 (83.3%) achieved CR, 16 (66.7%) by I1, 4 after I2. 4 patients never reached CR, 3 of them had a PR after I1. M5 patients did badly (2 early deaths, 2 PR, 4 CR). All patients without CR after I1 received the whole AML-BFM-83 protocol. Comparison of the results of the 2 studies revealed a similar CR rate for I1 (our patients) and I2 (BFM data): 80.0% vs. 82.2% (calculated for patients who ever reached CR). CR was reached before consolidation in all our CR patients compared to 82.2% of BFM patients. Early CR may be of long term prognostic significance. Cardiotoxicity of induction may be reduced by substitution of DNR by ACLA-A.

Aclarubicin↗
PubMed1986

Prognostic factors in acute lymphoid leukaemia of childhood. II. Cell surface markers.

Monoclonal sera have been used to determine the surface phaenotype of leukaemic cells during the last three years. Bone-marrow specimens of 57 children with recently diagnosed acute lymphoid leukaemia were examined; four cases were classified as T-cell leukaemia, 2 cases as B-cell leukaemia, in 37 cases cALLa was positive and fourteen children were classified as O-cell type, based on the absence of markers. Analysis of symptom-free survival revealed a very poor prognosis in B-cell leukaemia; there was no significant difference between the remaining groups. Within the cALLa positive cases L1 exhibited a markedly more favourable prognosis than L2.

Antigens, Neoplasm↗
PubMed1986

[New aspects of the determination of blood methotrexate levels in leukemic children].

Serum and CSF concentrations after medium dosage of methotrexate (MTX; 500 mg/m2 - 1,000 mg/m2) have been determined by an enzymatic assay during 142 infusions in children with ALL. If the dose of MTX was 500 mg/m2 MTX concentrations in CSF were under 10(-6) M/l in 40% of the treatments but only in 22%, when the dose was increased to 1,000 mg/m2. The systemic clearance of MTX was found to be increased significantly by the 2nd MTX treatment in children who relapsed thereafter. Such a phenomenon was not observed in children who continued in remission. The relapse free survival of children, whose MTX-clearance remained constant by the 2nd MTX treatment was significantly longer. No serious MTX toxicity has been observed in our patients.

Blood-Brain Barrier↗
PubMed1986

Prognostic factors in acute lymphoid leukaemia of childhood. I. Cytogenetic studies.

The results of chromosonal analysis of bone-marrow cells of 30 children with untreated acute lymphoid leukaemia are reported. On the basis of the modal chromosome number found in the cell clone showing the most frequent aberration, the patients could be classified into hypodiploid, pseudodiploid, hyperploid and normal groups. Pseudodiploidy predicted a poor prognosis while the survival rate of patients with normal or hyperploid chromosome counts was favourable.

Bone Marrow Examination↗
PubMed1986

Cytogenetic studies on peripheral blood cultures of neonates treated in an intensive unit.

The possible causes of an increased rate of structural chromosomal aberrations and sister chromatid exchange in peripheral blood cultures of mechanically ventilated newborns in an intensive care unit were investigated. No cytogenetic abnormalities were found in low-birth-weight babies affected by hypoxia and acidosis during their first week of life. The rate of chromosome breakage and sister chromatid exchange was increased in blood cultures of neonates continuously ventilated with 70-80 vol% oxygen for a long period of time. The incidence and degree of chromosomal damage, although showing wide individual variations, was related to the duration of oxygen treatment. In addition to high oxygen tension, other environmental factors of intensive care therapy like antibiotic and chemotherapeutic agents may be responsible for the mutagenic effect. The results indicate once again the importance of continuous pO2-monitoring of ventilated newborns.

Chromosome Aberrations↗