Biomedical subjects
Publications and source records attributed to S O Lie.
The seasonal and chronological distributions of birth dates of 820 patients with congenital hypothyroidism due to thyroid dysgenesis were analysed in eight areas in the world. The incidence had some seasonal variations in certain areas. These observations suggest that some environmental factors cause this disease.
Two groups of children with phenylketonuria were followed from birth for several years. The Recommended Dietary Allowance group received a protein intake as recommended by the Food and Nutrition Board. The Food and Agricultural Organization (FAO) group received a protein intake as recommended by FAO. The children were followed very closely for the biochemical control of the disease. The children were also followed very closely to evaluate the adequacy of the protein intake using length, weight, routine hematology, chemical analysis, and x-ray of the hand. The results indicated two groups of healthy children. However, a decline in length growth percentile was found in some of the FAO children. A possible osteoporosis developed in two of the FAO children. The possible conclusion that the FAO "safe level of intakes of egg or milk protein" is marginal is discussed.
The study is based on the material of acute leukaemia in Norway 1957-81 from the Cancer Registry of Norway. The age-adjusted incidence rates for both sexes have been unchanged. For childhood leukaemias (0-14 years at diagnosis) the age-specific incidence rates have been constant for both sexes and there has been an almost constant incidence for the 5 year birth cohorts 1950-69. Among adults there has been virtually unchanged age-specific incidence rates for most age-groups between 15 and 74 for both sexes. Among those older than 75 years, an increase is seen, most probably due to better diagnostic procedures. No geographic differences were found in age-specific incidence rates.
A 12-year-old boy with homocystinuria due to a cystathionine synthetase defect was shown to accumulate large amounts of pyroglutamic acid (pyroglu). In four different urine samples the concentration ranged between 4.1 and 9.7 mol/mol of creatinine. The pyroglu concentration in plasma was 1.6 mmol/l, and in erythrocytes 750 nmol/g cells. Normally only trace amounts are present. The pyroglu levels normalized during treatment with pyridoxine and folic acid. Accumulation of pyroglu has not previously been described in homocystinuria. Homocysteine can replace cysteine as a substrate for gamma-glutamylcysteine synthetase, an enzyme involved in the biosynthesis of glutathione, giving gamma-glutamylhomocysteine. This dipeptide is efficiently split by gamma-glutamylcyclotransferase to pyroglu and homocysteine. This reaction sequence most likely explains the accumulation of pyroglu in our patient. Ten other homocystinuria patients, who all had lower plasma levels of homocysteine, did not accumulate pyroglu. Our patient might either be a new variant, or more likely the pyroglu formation occurs only high levels of homocysteine.
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A male patient with fucosidosis exhibited the following characteristics: 1. Early onset and rapid progression of neurological symptoms. 2.Skin changes compatible with angiokeratoma corporis diffusum. 3. Complete or nearly complete deficiency of alpha-fucosidase. 4. Survival to adult age (20 years). The deficiency of alpha-fucosidase was demonstrated in liver, tears, urine, sediment, and cultured fibroblasts. We conclude that severe deficiency or complete absence of alpha-fucosidase does not by itself preclude survival to adult age.
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During the last 4 years, we have studied the adriamycin-DNA complex originally developed by Trouet and co-workers (1972). This paper summarizes the results of our pharmacologic and clinical studies. The complex is taken up by cells through an adsorptive pinocytosis, with DNA as the binding molecule. Excess DNA prevents uptake of the drug. Administration of the drug as the complex results in much higher serum concentration and a reduced urinary excretion. The complex is well tolerated, but side effects are probably of the same order as those seen with the free drug. An exception may be the heart. The acute toxicity is not seen when infusing the complex. Our experience with 20 children who have received more than 500 mg/m2 indicates that the chronic cardiac toxicity may be reduced, too. Spectacular, but anecdotal, results have been observed in a variety of solid tumors. Of 16 children with acute myelogenous leukemia, 14 went into a complete remission on a protocol of cytosine arabinoside in combination with the complex. Three of these children are now off therapy, with the longest observation period being 4 years and 4 months.
A male boy is described, who suffered from an intractable diarrhoea and several infections and who died in a severe marasmic state at the age of 8 months. Immunological studies revealed a block in the normal differentiation of B cells to Ig-producing plasma cells. After the age of 5 months, however, this block disappeared, leading to a dramatic increase in circulating Ig, most pronounced in the IgM class. In the intestine, plasma cells could only be detected after the age of 5 months, and then with a marked preponderance of IgM cells. Our results thus indicate a reversible block in the normal maturation of B cells in our patient. An older brother may have had a similar disease, suggesting a possible genetic basis for the disorder.
Urinary excretion of aspartylglycosamines was investigated in eight patients by semiquantitative thin-layer chromatography, and bound glycosamines by a quantitative photometric method (Elson-Morgan reaction). Each patient showed a fairly constant level, relative to the creatinine, of aspartylglycosamines in urine. The least retarded patient, aged 31, excreted about 350 mg/g creatinine, one-third of that found in two severely retarded young patients, aged 4 and 7 years (1400 and 940 mg/g creatinine, respectively). Three days on a low-protein diet did not change the aspartylglycosamine excretion in the patient showing the highest excretion rate.
The pharmacokinetics of adriamycin given as free and in DNA-complexed form was compared in six children with malignant disease. The two types of adriamycin were given to the same child at 3--4-week intervals, thereby excluding genetic variations when comparing the results. Plasma and urine were collected during and after the drug infusion, and the drug concentrations were measured by means of a sensitive fluorimetric procedure. The study shows that one obtains: 1. a much higher plasma concentration of adriamycin when it is given in the complexed form. 2. a lower urine excretion of adriamycin and fluorescent metabolites when adriamycin is administered as the DNA-complex.
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