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Biomedical subjects

S O Lie

Publications and source records attributed to S O Lie.

At least 55 records · Page 3Linked to original sources

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↗

[Medulloblastoma in children. A 20-year case load].

Between 1968 and 1987, seventy children below the age of 14 years were treated at one institution for cerebellar medulloblastoma. There were 41 boys and 29 girls. The 70 children included one pair of siblings. All the children have been followed up by one of the authors. During the first ten years, postoperative mortality within the first month was 17.5%. During the last ten years there was only one such death (3.5%). All children from the first ten-year period are dead. In the last ten-year period 25 of 35 children have survived (observation time 1-12 years, mean six years). This improvement is due to better surgical care and the use of post-operative irradiation and chemotherapy. Cerebral computerized tomography and magnetic imaging tomography are the investigational methods of choice for medulloblastoma today.

Adolescent↗

Acute myelogenous leukaemia in children.

Acute myelogenous leukaemia in childhood is considerably more resistant to chemotherapy than the acute lymphocytic leukaemias. Recently, more aggressive therapy has improved the outlook for children with this difficult form of leukaemia. Long-term disease-free survival of children achieving remission has been reported to be more than 40% in some studies. This paper reviews both the present concept of leukaemogenesis as well as some of the more recent therapeutic studies on childhood AML.

Child↗

Increased natural killer cell activity and numbers of Leu-7 and Leu-11b (CD 16)-positive cells in bone marrow of children in remission from acute lymphoblastic leukaemia.

Natural killer (NK) cell activity and related markers were analysed in childhood acute lymphoblastic leukaemia (ALL). Children with untreated ALL, children with active disease, and children in remission for less than 1 month and undergoing induction therapy had significantly lower NK cell activity in peripheral blood than the control group (P less than 0.05, P = 0.0005, and P less than 0.0025). Patients in remission for 1-3 months and undergoing consolidation chemotherapy had normal NK activity (P greater than 0.05). Children in complete remission for more than 3 months and undergoing maintenance therapy also had a normal NK activity in their peripheral blood (P greater than 0.05). However, their bone marrow cells showed an increased NK cell activity (P less than 0.0005). Cells positive for the Leu-7 marker were reduced in the peripheral blood from untreated children (P less than 0.025) and children in remission for less than 1 month (P = 0.025). The percentage of cells from peripheral blood expressing the marker Leu-11b (CD 16) did not differ significantly from that of the controls (P greater than 0.05). However, children in complete remission for more than 3 months had a higher number of bone marrow cells expressing the Leu-7 (P = 0.005) and the Leu-11b (CD 16) markers (P = 0.05) than controls. Stimulation of mononuclear cell suspensions with recombinant alpha interferon and recombinant interleukin 2 were shown to cause a normalization of the NK cell activity in peripheral blood and bone marrow.

Adolescent↗

Prognostic factors in neuroblastoma. Clinical, histopathologic, and immunohistochemical features and DNA ploidy in relation to prognosis.

Tumor samples from 58 patients diagnosed and treated for neuroblastoma or ganglioneuroblastoma in a single institution from 1967 to 1981 were included in a study of prognostic factors. Histopathology, certain immunohistochemical markers, and DNA ploidy were evaluated along with clinical variables such as tumor stage, primary site, and patient's age at diagnosis. Children under 1.5 years of age at diagnosis had a much better prognosis than did older ones, and this variable was the best prognostic indicator. Tumor Stages I to II and IVS, primary tumor site above the diaphragm, and tumor differentiation were also related to a better prognosis. The Shimada classification was of no additional prognostic value in our study. Neither was the immunohistochemical marker pattern, but it was sometimes helpful in establishing the tumor diagnosis. Tumor-cell ploidy, however, seemed to afford additional prognostic information because the 11 patients with aneuploid tumors under the age of 1.5 years at diagnosis all survived in contrast to only five of nine patients with diploid tumors in the same age group. It is possible that this was due to a better response to treatment in the aneuploid group. Our results suggest that patients with diploid neuroblastomas of undifferentiated histology and those over the age of 1.5 years at diagnosis might be selected for more intense treatment.

Adolescent↗

[Fever].

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Anti-Inflammatory Agents, Non-Steroidal↗

Altered natural killer cell activity in childhood acute non-lymphoid leukaemia. Augmented natural killer cell activity and cells expressing the Leu 7 and Leu 11b (CD 16) markers in the bone marrow of children in remission.

Peripheral blood and bone marrow mononuclear cells from 25 children with acute non-lymphoid leukaemia were analysed for natural killer cell activity and for cells with the Leu-7 and Leu-11b (CD 16) markers. Significantly reduced spontaneous cytotoxicity was detected in peripheral blood from children with untreated and active acute non-lymphoid leukaemia compared with that of the controls (P = 0.01 and P less than 0.05). Patients in remission, however, had normal natural cytotoxicity and normal numbers of Leu-7 and Leu-11b (CD 16)-positive cells. The natural killer cell activity in bone marrow from patients with untreated acute non-lymphoid leukaemia was also significantly reduced (P = 0.025). On the other hand, patients in remission had both an increased percentage of Leu-7 and Leu-11b (CD 16)-positive cells (P less than 0.05) and an increased natural killer cell activity (P less than 0.0005) in their bone marrow cells in comparison with the control group. This augmented natural killer cell activity is most probably a result of anti-leukaemic treatment. Stimulation with recombinant alpha interferon and recombinant interleukin 2 caused an increase in natural killer cell activity that was both significant and normal in both peripheral blood and bone marrow from children with acute non-lymphoid leukaemia.

Acute Disease↗

High-dose retinol in children with acute myelogenous leukemia in remission.

In a single-institution study, 23 consecutive children with acute myeloid leukemia (AML) have been treated with a protocol including doxorubicin, cytarabine and 6-thioguanine as induction therapy, followed by four courses of high-dose cytarabine as consolidation. Total duration of chemotherapy was 6-8 months from diagnosis. 21 out of the 23 children achieved complete remission. During remission, the children received 52 mumol (50,000 I.U.) retinol as retinyl palmitate per square meter daily. 14 of the 21 children are still in their first remission with a mean observation time of 36 months. In our study retinyl ester given in doses up to 30 times the recommended daily allowances has not caused any clinical or biochemical side effect for up to 4 yr of therapy.

Adolescent↗

Fasting plasma amino acid concentrations in PKU children on two different levels of protein intake.

Two groups of children with phenylketonuria were treated with different amounts of protein. One group (RDA group) received protein as recommended by the U.S. Food and Nutrition Board, the other (FAO group) the amount recommended by the FAO/WHO 1973 ad hoc Expert Committee. Two of the children in the FAO group showed a decrease in length/growth velocity which raised the question of the adequacy of the protein content in the diet. Since deviations from normal plasma amino acids have been observed in protein deficient, energy-adequate diets, we examined these parameters in the PKU children. In the two children with retardation in length/growth, very high glycine values as well as very high alanine values were observed at the end of the study. These observations strengthened our suspicion that the FAO/WHO 1973 recommendations are marginal.

Amino Acids↗

Human granulopoiesis in vitro--medium-dependent growth regulation by a granulocyte-derived inhibitor.

A number of reports have indicated that mature blood granulocytes produce regulators that inhibit proliferation of progenitor cells in the bone marrow. However, this concept of negative feedback of granulopoiesis is still controversial. To examine whether conflicting results may depend upon the experimental set-up, we have compared colony formation by human bone marrow cells in different growth media. Unmodified McCoy's medium, which in feeder layer cultures supports the formation of large numbers of colonies, was a poor growth medium in cultures supplied with crude or recombinant colony stimulating factor (CSF). The colony formation improved when the medium was supplemented with defined additives. In CMRL 1066 cultures, granulocyte extract (GRE) consistently caused a strong inhibition of colony formation. In contrast, with unmodified McCoy's medium, granulocyte extract enhanced colony formation in a dose-dependent manner. The enhancing effect of granulocyte extract coincided with low colony numbers in the control cultures. The stimulatory effect of granulocyte extract in McCoy's medium, switched to strong inhibition when thymidine, a component of CMRL 1066 medium, was added. The inhibitory and stimulatory activities were found in the same molecular weight fractions (30-60 kD) after gel filtration. Both modulators in granulocyte extract appeared to be independent of monocytes and T lymphocytes in the bone marrow, as shown by removal of these cells with magnetic microspheres coated with specific monoclonal antibodies. The present work shows that regulation of cell proliferation in vitro depends strongly on culture conditions, such as choice of medium. It appears that thymidine acts as co-factor for the inhibitor in granulocyte extract.

Bone Marrow Cells↗