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Biomedical subjects

R Hulhoven

Publications and source records attributed to R Hulhoven.

34 records · Page 2Linked to original sources
PubMed1982

[Aclacinomycin-A in acute leukaemias and leukaemic non-Hodgkin lymphomas (author's transl)].

Aclacinomycine-A (ACM), a new anthracycline derivative, was administered intravenously to 50 patients in doses of 10-30 mg/m2/day for periods of 6 to 30 days. Among the 45 patients who could be assessed, 17 were suffering from acute myeloid leukaemia, 19 from acute lymphoid leukaemia and 9 from non-hodgkin lymphoma. The results confirmed those first published by the authors in 1978 and led them to propose new measures aimed at reducing the toxicity of ACM. Depending on the dosage, complete or partial (more than 50%) remissions were obtained in patients with acute myeloid leukaemia. In the 19 patients with acute lymphoid leukaemia, complete remission was observed in 2 and partial remission in 2. Among the 9 patients with non-hodgkin lymphoma, there was 3 complete and 1 partial remissions. ACM did not produce alopecia and, as predicted by the authors' experimental study on hamsters, did not have major cardiac toxicity. The gastrointestinal toxicity, which had forced a reduction of the total dose in the first trial, proved moderate, even with normal dosage.

Aclarubicin↗
PubMed1982

Distribution of daunorubicin intravenously injected or intravenously infused as free drug and as a complex with DNA in rabbits.

The tissue distribution of daunorubicin (DNR) was investigated in rabbits after 5 mg/kg DNR i.v. bolus injection or 4 h infusion of 5 mg/kg either as free drug or as a complex with DNA. After i.v. bolus, the highest DNR concentration was observed in lungs and kidneys, a lower concentration in heart and spleen and the least in the liver. The DNR biotransformation to daunorubicinol (DNR-ol) and aglycones was most active in kidneys and liver, while heart, lungs and spleen metabolized DNR to a lower extent. The DNR tissue elimination half-life varied from 4.5 to 8.7 h, whereas concentrations of DNR-ol remained elevated for a longer period of time. After 4 h infusion, the only difference when compared with i.v. bolus consisted of a 3-fold lower initial DNR concentration in heart and lungs. No striking difference could be observed after free versus complexed drug infusion except for a somewhat lower DNR concentration in heart and lungs for the complexed drug.

Animals↗
PubMed1980

Uricosuric effect of fenofibrate in healthy volunteers.

The uricosuric properties of a single oral dose (300 mg) of fenofibrate, or isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl] propionate (LF 178), a new hypolipidemic drug, have been investigated versus placebo, benzbromarone, with and without urine alkalinization, in ten normouricemic male volunteers, following a crossover design. Twofold increased uric acid clearance values were obtained after fenofibrate and fourfold increased values after benzbromarone. The ratio urinary uric acid/urinary creatinine (UUA/UCr) was enhanced after fenofibrate and benzbromarone versus placebo. The urine alkalinization with fenofibrate intake did increase this ratio to a higher extent.

Adult↗
PubMed1980

A phase II study of vindesine in patients with hematological malignancies.

A phase II protocol associating vindesine and prednisone was used in 47 hematological patients of whom 40 were evaluable. The best results were achieved in relapses of childhood's ALL, with a high proportion of complete remissions and in blastic crises of CML. The efficacy appeared less in relapses of ALL in adults and of malignant lymphoma. The other cases seemed not to respond favorably. The hematological toxicity consisted of leucopenia generally of short duration, but sometimes severe. The neurological toxicity was little and led to reduction of the dosage in only two adults with preexisting neuropathy.

Child↗
PubMed1980

Daunorubicin, daunorubicinol and DNA plasma kinetics after I.V. administration of daunorubicin-DNA complex in the rabbit. II. -- Effects of R. E. S.-blockade.

Reticuloendothelial system-blockade induced by collodial carbon in rabbits produced only a single modification of the plasma kinetics of daunorubicin-DNA complex, consisting in a significant prolongation of the distribution phase of the vector (DNA). No changes in distribution and metabolism of the cytostatic drug (DNR) were observed. Thus, a lysosomotropic mechanism does not play a major role in the disposition of DNA-complexed DNR.

Animals↗
PubMed1979

Clinical trials with daunorubicin-DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood, acute nonlymphoblastic leukemia, and bronchogenic carcinoma.

Treatment with daunorubicin-DNA (DNR-DNA) or adriamycin-DNA (ADM-DNA) has been evaluated in acute lymphoblastic leukemia of childhood (ALL), acute nonlymphoblastic leukemia (ANLL) and bronchogenic carcinoma (BC). The Five-year survival rate in 69 children with ALL was 73.7% when ADM-DNA was introduced in the treatment and 38% with DNR-DNA (P = 0.03). A randomization between free DNR and DNR-DNA for remission induction in 26 patients with ANLL has shown that the drugs were of equivalent effectiveness. The one-year survival rate was 66% for the DNR group and 64% for the DNR-DNA group. In 59 patients with BC, a randomized trial between ADM-DNA and cyclophosphamide-vinblastine (CTX-VLB) did not show an advantage in favor of one of these treatments. In anaplastic BC (51 patients), there was no difference in survival rate or remission rate between patients treated with ADM or ADM-DNA. No cardiotoxicity was noted among the patients treated with the complexed drugs. ADM-DNA and DNR-DNA are as effective as the free drugs. Cardiotoxicity appears to be reduced.

Acute Disease↗
PubMed1979

Human pharmacokinetics of the daunorubicin-DNA complex. An alternative view of the lysosomotropic theory.

Plasma kinetics and urinary execretion of daunorubicin (DNR) and its active metabolite, daunorubicinol (DNR-ol) were studied in 15 leukemic patients after a 4-h infusion of 75 mg DNR/m2 either as the free drug or as a complex with DNA. The data obtained after infusion of the DNR-DNA complex were compared with the data obtained after infusion of the free drug. The DNR plasma levels were found to be higher during the 2 h following the infusion of the complex; the levels of DNR-ol were only higher for a few minutes after infusion. Kinetic analysis showed that complexing with DNA does not fundamentally modify the three-compartment model described for DNR. Only quantitative modifications were observed: a marked lengthening of the alpha-phase and a shortening of the gamma-phase. Urinary excretion of DNR and DNR-ol was increased after infusion of the complexed drug, in relation to the persistence of higher plasma levels. The data recorded in this work do not confirm the lysosomotropic mechanism postulated for the DNR-DNA complex, but show a delayed distribution of DNR, which is progressively released by dissociation of the circulating DNR-DNA complex, as previously demonstrated in rabbits infused under same conditions.

Adolescent↗
PubMed1978

Daunorubicin, daunorubicinol and DNA plasma kinetics after I.V. administration of daunorubican-DNA complex in the rabbit.

The pharmacokinetics of daunorubicin and daunorubin-DNA complex were studied in the rabbit after i.v. bolus injection and a 4hr infusion period. The plasma levels of daunorubicin and daunorubicinol were measured by high-pressure liquid chromatography and the DNA plasma levels by means of 125I labelled DNA. The results demonstrated a slower distribution of the complex; however, the more rapid decrease in the plasma levels of daunorubicin than that of DNA suggested that this complex essentially constitutes a "daunorubicin circulating pool" from which the drug diffuses more slowly than after the administration of uncomplexed daunorubicin.

Animals↗
PubMed1977

HPLC determination of daunorubicin and daunorubicinol in human plasma.

A high-performance liquid chromatographic method for the quantitative simultaneous measurement of daunorubicin and its active metabolite, daunorubicinol, at low concentrations in human plasma was described. The advantages of this method were specificity, sensitivity, minimal pre-analysis work-up and small sample size. The method was sensitive for plasma levels of daunorubicin and daunorubicinol as low as 10 ng/ml. Preliminary dosages on plasma from leukemic patients treated with a 4 hr infusion of 75 mg/m2 daunorubicin either as free drug or complexed with DNA were reported. The results suggested a slower disposition of the daunorubicin-DNA complex.

Chromatography, High Pressure Liquid↗
PubMed1976

Quantitative determination of low levels of daunomycin and daunomycinol in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the measurement of daunomycin and its main metabolite, daunomycinol, at low concentrations in plasma is described. Quantitative determinations were obtained by the use of adriamycin, another cystostatic anthracycline antibiotic, as an internal standard. The separations were carried out on a 5-mum silica microsphere column with a quaternary solvent mixture as eluent. The components in the eluted peaks were detected by visible absorption at 490 nm and there were no interfering peaks. The advantages of the method are specificity, sensitivity, minimal pre-analysis sample work-up and small sample size. The method is sensitive for plasma levels of daunomycin and daunomycinol above 10 ng/ml. Experimental animal data are presented to illustrate the application of the method.

Animals↗
PubMedDate not supplied

[Simultaneous study of karyotype and bone marrow histology in chronic myeloid leukemia with Ph1 chromsome. (author's transl)].

This study was devoted to the simultaneous examination of the karyotype and the bone marrow histology in 33 patients suffering from chronic myeloid leukemia with the Ph1 chromosome. Some patients were evaluated in the beginning of the disease, others after evolution and treatment and some at both times. Supplementary abnormalities of the karyotype occurred in some patients before any treatment, but in most after evolution and treatment. The abnormalities encountered consisted in hypodiploidies, modifications of chromosome structure and hyperdiploidies. The additional abnormalities of the karyotype were in the majority of the patients accompanied by a bone marrow histology characterized by more pronounced blastic infiltration and precollagen fibrosis and evidence of bone lesions. The picture realized by the karyotype and the bone marrow histology allows a better evaluation of the evolution and the prognosis is individual cases, especially of the likely hood of the acute blastic transformation.

Adolescent↗