Abnormal glucose tolerance in children with acute leukemia. Effect of induction chemotherapy including L-asparaginase.

The glycemic and insulin response to an oral glucose load was studied in 17 children with acute lymphoblastic leukemia (ALL) and 13 normal controls. The patients were randomly assigned to either group A, receiving prednisone and vincristine, or group B, receiving these agents and, in addition, L-asparaginase from days 9-19 of the study. The glucose load was performed prior to (phase I), and on days 8 (phase II), and 19 (phase III) of chemotherapy. The mean glycemic response in both groups of patients was significantly higher than in controls at diagnosis and prior to any treatment, while mean insulin levels were not significantly different from controls. One week after initiation of treatment, the mean glycemic response improved, and was associated with hyperinsulinism. After the second week of treatment, the mean glucose and insulin response curves in group A were similar to controls. In group B, while insulin values returned to normal, blood glucose levels remained higher than in controls, but not significantly so. These findings suggest that: 1) The leukemic process itself, through mechanisms as yet undetermined, causes impairment of glucose tolerance, and 2) the diabetogenic effect of L-asparaginase is not manifested in all patients.

Cytochemical demonstration of 5-formyl-tetrahydrofolate cyclodehydrase activity in leucocytes of patients with acute leukaemia.

The activity of 5-formyl-tetrahydrofolate cyclodehydrase has been studied cytochemically in leucocytes of children with acute leukaemia. Comparison of enzymatic activity in the same types of cells showed no significant variation between normal controls and the patients with acute leukaemia. The blast cells were weakly positive or negative. This finding is of very interest as the blast cells are capable of division. Probably the enzyme appears in the blast cells at some stage of the cell cycle. 2 populations of lymphocytes were observed, 1 positive with a few granules and 1 negative. A reduction of enzyme activity was observed after prophylactic cranial irradiation and methotrexate decreased enzyme activity in some patients.

Leucocyte glucose-6-phosphate dehydrogenase (g-6-pd) activity in g-6-pd deficient subjects.

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied in the following group of Greek people. Group 1: 43 male children and 16 male students with mean values of enzyme activity of 27.7 +/- 16.6 units and 24.6 +/- 5.6 units, respectively. Group 2: 15 G-6-PD deficient male children who had never experienced an acute haemolytic episode with a mean value of 10.8 +/- 4.6 units. Group 3: 19 G-6-PD deficient male children during favism and 3 months after the haemolytic crisis with mean values of 8 +/- 4 units and 9.2 +/- 1.9 units, respectively. Group 4: 19 mothers of children from group 3 who by definition were carriers of G-6-PD deficiency had a mean value of 18.2 +/- 8.2 units. The difference between means for group 1 and groups 2, 3 and 4 is highly significant (P < 0.001). Therefore the enzymatic defect in Greek people is not limited to the erythrocytes but can be also demonstrated in leucocytes.

Serum levels of retinol, retinol-binding protein, carotenoids and triglycerides in children with beta-thalassemia major.

Levels of retinol (vitamin A), carotenoids and triglycerides in the serum of 50 children with homozygous beta-thalassemia have been studied, as well as the ability of the small intestine to absorb a test meal containing retinol palmitate, triglyceride, d-xylose and glucose. On the other hand, 8 patients underwent a dark-adaptation test, and in 40 children with homozygous beta-thalassemia the levels of retinol-binding protein in the serum were estimated. The mean levels of retinol, carotenoids and triglycerides in the serum of the patients were: 23 +/- 4.1 micrograms/dl (controls: 36.3 +/- 4.9), 44 +/- 15.5 micrograms/dl (controls: 103 +/- 24), 117 +/- 20 (controls: 126 +/- 26), respectively. The absorption from the small intestine of retinol, triglycerides, glucose and d-xylose was normal. 6 out of 8 patients studied for visual function showed an abnormal dark-adaptation test, and these 6 children had low serum retinol levels. Finally, the mean serum levels of retinol-binding protein in the patients were 4.74 +/- 0.53 mg/dl (controls: 5.63 +/- 0.58). The low retinol levels were correlated with the low retinol-binding protein values which, in turn, could be due to the abnormal liver function of the patients.

Relationship between tocopherols and serum lipid levels in children with beta-thalassemia major.

Serum tocopherol levels were found to be below normal (less than 0.5 mg/100 ml) in nine (50%) of 18 children with beta-thalassemia major receiving inadequate treatment with blood transfusions. The mean tocopherol levels were significantly lower in the children with beta-thalassemia (0.57 mg/100/ml +/- 0.20) than in the controls (1.08 mg/100 ml +/- 0.24). Serum total lipid levels were found to be low in children with beta-thalassemia. The difference between the mean total lipid level in the beta-thalassemic patients (365 mg/100 ml +/- 75) as compared to that of the controls (581 mg/100 ml +/- 94) was highly significant (P less than 0.01). The ratio of serum tocopherol to 1 g total lipids was lower in children with beta-thalassemia (1.41 mg/100 ml +/- 0.43) than in the controls (1.88 mg/100 ml +/- 0.46) and the difference was significant. Yet, only three out of the 18 children with beta-thalassemia showed a ratio of less than 0.8 mg/100 ml tocopherol per 1 g total lipid which may be considered indicative of tocopherol deficiency.

Irradiation of the head. Immediate effect on growth hormone secretion in children.

Plasma growth hormone (GH) was determined in samples obtained hourly from 1000 h to 0700 h before, and after a 3 week course of "prophylactic" cranial irradiation, in ten leukemic children who had no clinical or laboratory evidence of central nervous system involvement. The mean per hour value of GH prior to irradiation (4.1 +/- 2.4 ng/ml) was similar to that of 7 endocrinologically normal children (4.09 +/- 2.4 ng/ml), a finding strongly suggesting normal pituitary function prior to irradiation. Following irradiation GH levels at each hour were, in general, lower than before. The difference is statistically significant at 0100 h. The peak GH responses were lower following than preceeding irradiation (p less than 0.02). The findings suggest an immediate suppressive effect of irradiadiation on the apparently normal hypothalamic pituitary axis in children.

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

[Epidemiology of acute leukemia of childhood in Greece (author's transl)]. / Epidémiologie de la leucémie aiguë chez l'enfant en Grèce

A retrospective study of 151 aged less than 15 years children suffering from acute leukaemia is reported, the parameters studied were male: female ratio, type of leukemia, age and seasonal distribution of the illness. The disease started in spring in 53 children (35,1%), in summer in 34 (22,6%), in autumn in 36 (23,8%) and in winter in 28 (18,5%). The difference between spring and winter was statistically highly significant (X2 = 10,54, P less than 0,005). Sixty two children (41%) were 3-5 years old. The male female ratio was 1.75. The disease was of the acute lymphoblastic type in 88,1% of the cases.