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Biomedical subjects

F C de Waal

Publications and source records attributed to F C de Waal.

At least 19 recordsLinked to original sources
PubMed1992

Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage.

UNLABELLED: Gonadal function was evaluated in 23 men (aged 14.8-28.8 years) treated in childhood with cytotoxic drugs for a solid tumour. Group 1 (N = 14) had been treated with non-alkylating drugs only, while group 2 (N = 9) received the alkylating drug cyclophosphamide in addition (range 3.8-19.5 g/m2). Median age at the start of treatment was 4.6 years (range 0.6-16.1) in group 1 and 13.9 years (range 3.7-16.9) in group 2. Data of the patients were compared with a reference group consisting of 14 normal men. Almost all patients of both groups showed normal development of puberty; 13 of the 14 men in group 1 showed normal hormonal values. In group 2, basal LH and FSH as well as the LH and FSH responses to GnRH showed higher levels compared to those of a reference group (p less than 0.001). Correlation analysis showed an evident correlation between the total dose of received cyclophosphamide and the basal FSH level (r = 0.78; p = 0.002), the FSH response to GnRH (r = 0.73; p = 0.002) and the LH response to GnRH (r = 0.67; p = 0.002). There was no correlation between the hormonal parameters and the doses of the other cytotoxic drugs. Semen analysis showed azoospermia in four boys of group 2 and in none of group 1. Two patients in group 2 had an elevated FSH response to GnRH while their semen analysis was normal. CONCLUSIONS: (1) There is a dose-response relationship between the basal FSH, the LH and FSH responses to GnRH and the dose of cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Prognostic value of morphometry in acute lymphoblastic leukemia of childhood.

The prognostic value of morphometric features was studied in a group of 33 children with acute lymphoblastic leukemia (ALL) and compared with clinical and hematologic parameters. Air dried, May-Grünwald-Giemsa-stained specimens were prepared from iliac crest biopsies, and for each patient, 150 blasts and their nuclei were selected according to a stratified selection method and measured on a graphic tablet system. Univariate overall survival analysis showed the French-American-British (FAB) classification to be the strongest clinical parameter (P less than .0001). However, the significance was mainly due to the fact that both L3 cases died; the results for L1 and L2 were less satisfactory, with a survival rate (at 10 years) of 69% for the 26 L1 cases and 80% for the five L2 cases. The nuclear/cytoplasmic (N/C) ratio was the best morphometric feature (P less than .0001) and provided more satisfactory classification results than did FAB: only 2 of the 21 (10%) cases with N/C ratios greater than 0.90 died (7 and 9.5 years after the diagnosis, respectively), and 9 of the 12 (75%) cases with N/C ratios greater than or equal to 0.90 died. For recurrence-free survival analysis, essentially the same results were obtained. The N/C ratio retained its significant prognostic value after recurrence: 11 of the 15 patients with eventual recurrences died; 9 of them had an (original) N/C ratio less than or equal to 0.90. Three of the four recurring cases that survived after recurrence had an N/C ratio greater than 0.90 (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1990

[A child with neonatal allo-immune neutropenia].

A newborn child with neonatal neutropenia as a result of the presence of maternal IgG isoantibodies against neutrophil granulocyte blood group antigens is reported. Mechanism, diagnostics and therapy of the disease are discussed. The diagnosis not only has consequences for the child, but also for the mother and following pregnancies. A review of the most important causes of neonatal neutropenia is given.

Blood Group Antigens↗
PubMed1989

Low dose cytosine-arabinoside has only minimal differentiation inducing capacity in HL60 cells.

Cytosine-arabinoside (ARA-C) in low doses induces complete remissions in myelodysplastic syndromes and acute leukemia. Evidence is accumulating that these remissions are not reached by differentiation induction but through cytotoxicity. In HL60 cells differentiation was measured by a comprehensive panel of quantitative and qualitative markers of maturation. After exposure to ARA-C (10(-7) M) for 4 days HL60 cells did not mature morphologically. Cell volume increased. The increase in esterase activity was small and did not reach the amount measured in normal monocytes. There was no significant difference in latex phagocytosis and NBT reduction between cultures with and without ARA-C. HL60 cells were arrested in S-phase and clonogenic capacity persisted. The observed changes after exposure to ARA-C seem to be caused by impeded cell division while synthesis of protein continues. We conclude that ARA-C in low dose exerts its effect by halting proliferation through cytotoxic effects and not by differentiation induction.

Cell Differentiation↗
PubMed1988

DUP 785 (NSC 368390): schedule-dependency of growth-inhibitory and antipyrimidine effects.

DUP 785 (NSC 368390; Brequinar sodium) is a new inhibitor of pyrimidine de novo biosynthesis with antitumor activity against several experimental tumors. DUP 785 inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking the conversion of dihydroorotate to orotate. We examined the influence of exposure time to DUP 785 on its growth-inhibitory effects in L1210 murine leukemia and WiDR human adenocarcinoma cells and the effects of pyrimidine (deoxy) nucleosides on reversal of growth-inhibition. The results were correlated with changes in intracellular pyrimidine nucleotide pools and cell cycle distribution. In L1210 cells, a continuous exposure to 25 microM DUP 785 up to 96 hr caused complete growth inhibition. A 2 hr exposure of cells to the drug did not affect growth. In WiDR cells, exposure to the drug for 1-24 hr, followed by cultivation in drug-free medium resulted in recovery of growth. However, cells exposed to the drug for 48 hr or longer were not able to resume growth when recultured in drug-free medium. Reversal studies were performed to know whether selective depletion of one of the pyrimidine (deoxy) nucleotides might be related to the growth-inhibitory effects of DUP 785. Neither thymidine, deoxycytidine alone, deoxycytidine plus tetrahydrouridine; nor cytidine plus tetrahydrouridine added after 24 hr were able to reverse cell growth inhibition induced by 25 microM DUP 785. However, uridine and cytidine alone reversed growth inhibition. UTP and CTP pools in L1210 cells decreased to about 30-40% of control levels after 4 hr of drug exposure, while dTTP and dCTP pools decreased to about 30% of control levels. There were no significant changes in purine nucleotide pools. In WiDR cells, UTP and CTP pools decreased rapidly after drug exposure and were substantially depleted after 24 hr. Reculture of cells in drug-free medium resulted in a significant recovery of UTP and CTP levels only for cells exposed to DUP 785 for 1-24 hr. For cells exposed to the drug for 48 and 72 hr recovery of nucleotide pools was minimal. In L1210 cells, a 12-hr exposure to the drug caused an accumulation of cells in the early S-phase. In WiDR cells, there was a clear accumulation of cells in the S-phase of the cell cycle after 24 hr drug exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Immunological phenotype of lymphoid cells in regenerating bone marrow of children after treatment for acute lymphoblastic leukemia.

Bone marrow samples from 8 children treated for acute lymphoblastic leukemia (ALL) were investigated at cessation of cytostatic treatment and during 18 months thereafter. The course of the percentage of lymphoid cells and characterization of these cells by means of monoclonal antibodies, peanut agglutinin (PNA) binding and S-phase determination are shown. The percentage of lymphocytes rises in the first 1.5 months, followed by a non-significant decline. The percentage of cells in S-phase is higher at 0 months than at 6, 15 and 18 months. The percentage of T-cells does not change significantly. In the first 1.5 months a sudden rise in the percentage of common-ALL-antigen (cALLA)-positive lymphocytes occurs. The number of B-cells rises to a peak at 6 months. PNA positively increases to a maximum at 3 months and is correlated with positivity for markers of the B-cell lineage. The percentages of B-cells, cALLA-positive, and PNA-positive lymphocytes do not change significantly after they reach their maximum values and are still high at 18 months. Our results show that after cessation of chemotherapy for ALL a lymphoid cell regeneration occurs in the bone marrow consisting of cells of the B-cell lineage; many of these are cALLA-positive, but are discernible from their malignant counterparts by PNA-positivity.

Antibodies, Monoclonal↗
PubMed1988

[Sedation and analgesia in interventions].

Children with leukemia have to undergo many times painful procedures like bone-marrow aspiration and lumbar puncture. For reduction of anxiety and pain sensation good psychological support can be an important help. Often sedative drugs are used, or even general anaesthesia may be necessary. There is a need of a safe, short-acting and effective medication. Among the different possibilities the intravenous or rectal administration of midazolam seems to be very promising.

Analgesics↗
PubMed1987

Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI.

A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted a MRI appearance allowing us to exclude tumor outgrowth into the brain.

Bone Neoplasms↗
PubMed1987

Quantitative enzyme determination; a parameter for leukemic cell differentiation.

In acute myeloid leukemia the leukemic cells are thought to be blocked in their normal differentiation. The stage of differentiation is the basis for the FAB classification. Induction of cell differentiation is a new and promising development in the treatment of some myeloproliferative diseases. The criteria for cell maturation and differentiation are almost all based on the morphology of the leukemic cells. In this study we tried to specify the maturation stage of the leukemic cells by quantitative enzyme analysis. In the HL60 (promyelocytic) cell line cells we determined the following enzymes: myeloperoxidase; alpha naphthyl acetate esterase; alpha naphthyl butyrate esterase and lactate dehydrogenase. The enzyme profiles obtained after culturing the cells in the presence of the differentiation inducing agents 1:25 dihydroxy vitamin D3 and DMSO were compared with several cytochemical and functional parameters. The results obtained in this study show that quantitative enzyme analysis is a useful tool in the study of myeloid or monocytic differentiation.

Calcitriol↗
PubMed1987

Relation between leukaemic cell count and degree of maturation in acute myeloid leukaemia.

In acute myeloid leukaemia the peripheral leukocyte count is known to be a prognostic factor. The preserved capacity of leukaemic cells to mature has also been suggested to be one. In a series of 179 cases of adult acute myeloid leukaemia peripheral leukaemic cell count and degree of maturation were found to be inversely correlated. As the degree of maturation of leukaemic cells in peripheral blood was lower than that in bone marrow in the majority of cases, blast cells appear to be released more easily from the marrow than cells that have matured to some extent in the direction of the larger promyelocytic or promonocytic cell type. In a series of 35 cases we found peripheral blast cells to be smaller than those in bone marrow. Moreover, central blast cell diameter and peripheral leukaemic cell count were inversely correlated. Therefore, leukaemic cell size or some factor related to it may contribute to the preferential egress of small immature cells from the marrow. Differences in proliferative activity could not account for the inverse correlation between degree of maturation and leukaemic cell count.

Adult↗
PubMed1985

Unreliability of beta-2-microglobulin in early detection of central nervous system relapse in acute lymphoblastic leukemia.

The value of serial determination of the cerebrospinal fluid (CSF) beta-2-microglobulin (Beta 2m) level for early detection of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) has been prospectively studied in 30 children. Beta 2m was determined by micro-ELISA assay. Results demonstrated a sensitivity of 40% (95% confidence interval, 5.3-85.3%) and a predictive value of 8% (95% confidence interval, 1.0-26.0%). In post-irradiation syndrome, as well as in viral infection with cytopathological changes of white cells in CSF, beta 2m values proved to be significantly higher than in incipient CNS relapse, and these conditions, or an unknown cause, are more often associated with beta 2m elevation than CNS relapse. No relation was found between CSF white cell counts and beta 2m levels. It is concluded that beta 2m is not an appropriate test for early detection of CNS involvement in children with acute lymphoblastic leukemia.

Central Nervous System↗
PubMed1985

Handmirror cells in childhood acute lymphoblastic leukemia related to immunological phenotype.

In 96 cases of childhood acute lymphoblastic leukemia (ALL), handmirror cells (HMCs) were counted in cytospin preparations of washed lymphoblasts obtained at diagnosis. HMC counts were significantly lower in T-ALL as compared to C-ALL (p less than 0.001). In T-ALL and pre-T-ALL 2/35 cases had more than 10% HMCs; in C-ALL 22/41 cases had more than 10% HMCs. In two cases of B-ALL 19% and 36% HMCs were found. Thus, HMC expression in ALL is related to the immunological phenotype, especially found in ALLs originating along the B-cell lineage.

Adolescent↗
PubMed1985

Bone marrow mitotic index: a methodological study.

The mitotic index (MI) of bone marrow specimens is assessed in 3 different ways: method I determines the number of mitotic figures per 1,000 nucleated cells; method II counts the number of mitoses seen per 1,000 nucleated cells belonging to the proliferative pool, and method III is the same as method I, but excludes all lymphoid cells. 30 Giemsa-stained bone marrow smears from 6 children were screened by 3 independent investigators. MI of method II is found to be approximately twice as high as the MI of method I. The results of method III indicate that the size of the lymphoid population introduces a bias, which renders method I less reliable. It is concluded that method II is the method of choice for a reliable assessment of bone marrow MI.

Bone Marrow Cells↗
PubMed1979

Neuroblastoma with a fulminant clinical course caused by tumor embolism.

The case of a 2 1/2-year-old girl with a well-nigh asymptomatic neuroblastoma of the left adrenal is described. In the final stage it gave rise to unusual clinical signs. The tumor had grown into the inferior vena cava via the left suprarenal and renal veins. Dissolution of the soft tumor mass in the vena cava caused fatal massive embolism of lungs and brain.

Adrenal Gland Neoplasms↗