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Biomedical subjects

S O Lie

Publications and source records attributed to S O Lie.

At least 19 recordsLinked to original sources

Differential chromatin structure-dependent binding of 7-aminoactinomycin D in normal and malignant bone marrow hematopoietic cells.

Chromatin structure-dependent binding of the DNA-specific dye 7-aminoactinomycin D (7-AMD) in leukemic and normal cells in bone marrow aspirates from childhood acute leukemia patients and patients without bone marrow neoplasia was assessed by multiparameter flow cytometry. Simultaneous staining with fluorescein isothiocyanate-labeled antibodies was needed in many cases for determination of the immunophenotype of the cells that exhibited differential binding of 7-AMD. 7-AMD binding was enhanced in normal (4 patients) and malignant (8 patients) myeloid cells, and was generally low in normal and leukemic lymphocytes and normoblasts. Four of 18 aspirates from 16 patients with acute lymphoblastic leukemia contained neoplastic cells with increased 7-AMD binding capability. The 7-AMD binding of the leukemic cells was not correlated to S-phase fraction (P = 0.07), but was significantly correlated to cell size as measured by forward angle light scattering (r = 0.49, P = 0.007). Patients with tumor cells exhibiting low 7-AMD binding at last aspirate survived significantly longer than the patients with leukemic cells binding high amounts of 7-AMD (P = 0.03). Neither cell size, S-phase fraction, nor ploidy status predicted patient survival in this small scale study.

Antigens, CD

VACTERL or MURCS association in a girl with neurenteric cyst and identical thoracic malformations in the father: a case of gonosomal mosaicism?

We report on a female infant with lethal congenital malformations including extreme hydrocephalus due to aqueductal stenosis, vertebral segmentation anomalies, fused costae, anal atresia, renal dysplasia, and bicornuate uterus with a double blind vagina. The VACTERL and the MURCS associations are possible diagnoses. Her father had a neurenteric cyst in infancy. He has identical vertebral and costal malformations as his daughter but is otherwise healthy. The possibility of dominant inheritance with gonosomal mosaicism in the father is discussed.

Abnormalities, Multiple

Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood.

In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment.

Age Factors

Progress in the treatment of childhood leukaemias.

The Nordic Society for Pediatric Hematology and Oncology (NOPHO) has run a population-based registry on all cases of acute leukaemias in the Nordic countries since 1981. Data on close to 2000 children with these diagnoses are presented and used as a background for a general discussion of progress in the therapy of these challenging conditions. Our material is unique in that it is population based. The results obtained are comparable to those obtained by all other major cooperative groups. Since January 1992, the treatment protocols for all types of acute leukaemias in childhood have been harmonized in the Nordic countries.

Adolescent

Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias.

The bone marrow stromal cell-derived growth factor interleukin-7 (IL-7) is known to stimulate growth of normal human B-cell precursors. In the present report, we have examined the effect of IL-7 on neoplastic B-cell precursors. Leukemic cells from 20 patients with common acute lymphoblastic leukemia (ALL) were highly purified by removing contaminating T cells and monocytes by rosetting with immunomagnetic beads. IL-7 markedly reduced the DNA synthesis in leukemic cells from three patients. This inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of the differentiation antigens CD19, CD20, CDw75, and surface mu-chain, and a decreased expression of terminal deoxynucleotidyl transferase. By examining G1 parameters, such as MYC, 4F2, and transferrin-receptor levels analyzed by flow cytometry as well as RNA and the cell cycle regulated antigen Ki67, it appeared that the cells were inhibited late in G1. Leukemic cells from the majority of the cases (12 of the 20 patients) responded to IL-7 with enhanced DNA synthesis without detectable maturation, as has been reported for their normal counterparts. Low molecular weight B-cell growth factor greatly potentiated the IL-7-induced growth stimulation of these cells. Thus, we have shown that IL-7 is capable of inhibiting proliferation of leukemic cells isolated from a subgroup of ALLs, and that this growth inhibition is accompanied by maturation of the cells.

Antibodies, Monoclonal

[Children and diseases in the Third World].

Each year approximately 137 million children are born, 70 million of them in countries where the mortality rate for under-fives exceeds 100 per 1,000. In worst-off Afghanistan 300 per 1,000 children under five die. We review some of the most common causes of this catastrophy: diarrhoea, acute respiratory infections, measles, malaria, and neonatal tetanus. All of the numerically significant contributors to under-five mortality are treatable and/or preventable by simple and inexpensive methods. Medical personnel from industrialized countries, and there is an increasing need for transfer of financial resources from highly developed to developing countries. The living conditions of children in the third world involve many factors that are detrimental to both physical and mental health. In order to effect a change, all countries and societies must become involved.

Age Factors

Management of pediatric pontine gliomas.

We present 36 consecutive patients with intrinsic glioma of the pons. Tumors with exophytic expansion were excluded. There were 16 females and 20 males, ranging in age from 2 to 13 years, median 6 years. The most common presenting symptoms were cranial nerve dysfunction, unsteadiness of gait, and hemiparesis. Computed tomography (CT) showed a hypodense (17/21) or isodense (4/21) expansion of the pons. Five tumors had areas of contrast enhancement. Following information about prognosis and possible types of management, parents decided for or against radiation therapy: twenty-four children underwent irradiation and 12 did not. Median survival among children receiving a full course of irradiation was 280 days, compared to 140 days in an equivalent group of non-irradiated children. Hemiparesis presenting without cranial nerve symptoms and contrast enhancement on CT scan were poor prognostic factors, whereas sex, age, and duration of symptoms at diagnosis were unrelated to prognosis.

Adolescent

Intellectual development in children with congenital hypothyroidism in relation to recommended thyroxine treatment.

The relationship between the treatment serum thyroxine level and intellectual development at 2 and 6 years was investigated in 46 Norwegian children with congenital hypothyroidism identified by neonatal screening. The level of serum thyroxine during the first 2 years was positively correlated with the Mental Development Index at 2 years of age (Bayley Scales of Infant Development) and the Verbal IQ at 6 years of age (Wechsler Preschool and Primary Scale of Intelligence). Children with a mean serum thyroxine level greater than 180 nmol/L (14 micrograms/dl) during the first year had a significantly higher Mental Development Index at 2 years and Verbal IQ at 6 years than children with serum thyroxine values less than 129 nmol/L (10 micrograms/dl). Boys had a lower Mental Development Index at 2 years of age than girls (86.9 vs 105.1; p less than 0.001) and a higher frequency of elevated serum levels of thyroid-stimulating hormone during the first year (p = 0.001). No signs of toxic effects of a high hormone level at the time of IQ assessment were detected. However, high serum levels of thyroxine at ages 2 to 4 years in girls were related to lower Performance IQ at age 6 years. The results demonstrate that the serum level of thyroxine is of importance in relation to intellectual development. Thyroxine levels above the upper reference range during the first 2 years were related to best intellectual development at 2 and 6 years.

Analysis of Variance

[Autologous bone marrow transplantation in children--experience with neuroblastoma].

Autologous bone marrow transplantation permits the use of greatly intensified cytoreductive therapy for cancer. Since 1983 seven children with disseminated neuroblastoma (stage IV) were treated by this method. Five were treated in first, and one in second complete remission; one child was in partial remission. Tumor cell purging of the marrow inoculum was performed in five cases. All children had engraftment and were discharged from hospital free of disease. Relapse was observed in three children within two years. Four children remain healthy at follow-up 5-77 months after autotransplantation. We describe and discuss indications, methods, side effects and results.

Abdominal Neoplasms

Quenching of Hoechst 33258 fluorescence in erythroid precursors.

Quenching of the fluorescence of DNA-bound Hoechst 33258 in erythroid precursors was studied by flow cytometry and cytochemistry. This quenching artifact may affect the measurement of ploidy in specific cases. The bone marrow cells of two patients with hemolytic disease and active erythropoiesis contained subpopulations of cells with an apparent hypodiploid DNA content as measured by flow cytometry of paraformaldehyde-fixed cells stained with Hoechst 33258. No aneuploidy was detected in either of the two cases when cells were stained with mithramycin or 7-aminoactinomycin D. Cells exhibiting reduced Hoechst 33258 fluorescence expressed glycophorin A and low amounts of CD36, and were therefore erythroid precursors. In one case studied, the number of cells with reduced Hoechst 33258 fluorescence and glycophorin A expressed agreed well with the number of cells containing nuclear hemoglobin. In the other case, hemoglobin was present in a significant proportion of nucleated cells. Calculated values for the efficiency of resonance energy transfer from Hoechst 33258 to hemoglobin were in accordance with the observed levels of quenching (approximately 10%). However, the results could also be explained by hemoglobin reabsorption of Hoechst 33258 fluorescence. Nuclei stained with Hoechst 33258 showed uniform fluorescence, probably due to extraction of hemoglobin during the isolation procedure.

Benzimidazoles

Children in the Norwegian health care system.

Norway is a large, sparsely populated country with a long tradition of socialized health care. The health status of Norwegians is good, with life expectancy among the highest in Europe. Indicators of infant health are also good, although not among the best. Health services in Norway are in principle free of charge to all citizens, and the current health expenditure is about 6.8% of the Gross National Product. Preventive and curative pediatric services account for only 3% of this total. The structure of Norwegian health and social services is presented in this discussion, both in general terms and with particular attention to services for children.

Adolescent

Postneonatal mortality in Norway: a study of recent trends and comparison with other mortality rates in Norwegian children.

Postneonatal mortality in Norway decreased rapidly from 1956 to 1980 but subsequently remained stable. In recent years the postneonatal death rate appears to be increasing, primarily due to greater numbers of deaths attributed to the Sudden Infant Death Syndrome. During the same period, mortality among older children has also decreased, with the decline evident in all leading causes. Only among people aged 15 to 19 years have recent trends been less than encouraging, with the number of fatal traffic accidents in particular remaining stable or increasing. Although there is room for continued improvement, the widely held belief that the health status of Norwegian children is good is supported by the trends in mortality.

Accidents, Traffic

Pharmacokinetics of oral 6-mercaptopurine: relationship between plasma levels and urine excretion of parent drug.

Plasma levels and cumulative urine excretion of 6-mercaptopurine (6-MP) were measured using a specific and sensitive high-performance liquid chromatographic assay in seven children with acute lymphoblastic leukemia (ALL) as well as in one healthy volunteer. The dose of 6-MP varied in the range of 25-75 mg/m2 of body surface area and was administered with a standard breakfast. A 4- to 11-fold variation between individuals was found in the pharmacokinetic parameters: peak concentration, time to reach peak, area under the plasma concentration-time curve (AUC), and fraction of dose excreted in the urine. Three repeated determinations in one individual revealed that AUC also varied more than sixfold following an overnight fast. In three individuals, the reducing agents glutathione (10 mg/kg) and ascorbic acid (15 mg/kg) were coadministered with 6-MP to evaluate their possible role in the protection of 6-MP from oxidation and degradation in the intestinal lumen. No consistent effect was observed, however, on the AUCs of either of these agents. A clear relationship was found between AUCs and the 24-h urinary excretion of unchanged drug (r = 0.9381), indicating that determinations of 6-MP in the urine may replace the painful procedure of repeated blood sampling. Further studies are necessary to determine the factors contributing to the unpredictable plasma levels following oral doses of 6-MP and to determine the value of pharmacokinetic monitoring in ALL patients.

Administration, Oral