SERIAL DETERMINATIONS OF SERUM FERRITIN IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA Evaluation of its Usefulness as a Prognostic Index

Abstract. Thirty children with acute lymphoblastic leukemia were monitored with serial serum ferritin determinations for up to 17 months. In children with acute lymphoblastic leukemia before initiation of therapy, or in relapse, the mean serum ferritin concentration was 636 μg/l. In children who went into primary remission, the mean serum ferritin concentration fell from 265 μg/l prior to start of treatment, to 161 μg/l after 3 months of treatment. Five patients relapsed. Their serum ferritin levels prior to the relapses ranged from 7 to 135 μg/l. At the time of relapse a further increase in serum ferritin was found in only 2 of the children. Thus, whereas high serum ferritin levels may signal disease activity in acute lymphoblastic leukemia, a normal serum ferritin level does not exclude disease activity or impending relapse.     

INFLUENCE OF ORAL LYSOZYME ADMINISTRATION ON SERUM IMMUNOGLOBULIN AND INTESTINAL SECRETORY IgA LEVELS IN INFANTS

Abstract. The influence of lysozyme feeding on the production of serum immunoglobuiins and intestinal secretory IgA was studied in full-term and premature infants, from birth up to the age six months. Serum immunogiobulins were not influenced by lysozyme administration. An increase in secretory IgA was found in stool filtrates of full-term Iysozyme-fed infants; no secretory IgA was detected in controls. In this way lysozyme feeding partly substituted for passive transfer of secretory IgA from maternal milk.     

ALLOGENEIC CORD BLOOD TRANSPLANTATION IN CHILDREN WITH HEMATOLOGICAL MALIGNANCIES: A Long-Term Follow-Up Single-Center Study

Forty-two consecutive pediatric patients with high-risk leukemia who received cord blood (CB) transplantation at the authors’ institution from January 1996 and December 2007 were included in this study. Age ranged from 6 months to 18 years and body weight from 7 to 73 kg. Twenty-nine patients had ALL and 13 AML. Twenty-seven out of 42 patients were transplanted in advanced phase of disease (beyond 2nd CR). For 13 patients the CB transplantation was their second transplant. The median follow-up for survivors was 60 months (range, 6–120 months). The probability of myeloid engraftment was 95 ± 5% and the median time to neutrophil >500/μL was 20 days (range, 12–54). The median time to platelet engraftment was 60 days (range, 37–200). The probability of relapse was 33 ± 9%. The nonrelapse mortality at day +100 after transplantation was 30 ± 7%. The probability of disease-free survival was 34 ± 7%. The CD34⁺ cell dose had a significant impact on DFS (HR, 3.28; 95% CI: 1.49–7.23; p =. 003). The results from a long-term follow-up study suggest that cord blood transplantation should be performed in the early phase of disease whenever possible. The cord blood unit for transplantation in pediatric patients with hematological malignancies should be chosen based on cell dose, especially a CD34⁺ cell dose.     

急性白血病患儿血清肿瘤坏死因子a的活性变化及临床意义

用放射免疫方法测定了2O例正常儿童及40例急性白血病（AL）患儿化疗前后血清肿瘤坏死因子（TNF－a）浓度。结果；在AL诊断时，TNF－a水平显著升高1当患儿获得部分缓解至完全缓解时，TNF－a水平呈梯形降低，其最低值仍高于健康儿童（P＜O．01～0．05）；22例急性淋巴细胞白血病（ALL）患儿TNF－a水平在任何阶段都比18例急性非淋巴细胞白血病（ANLL）患儿低（P＜0．o1）；TNF－a水平和临床疗效之间显示负相关性。因此，作者们认为测量TNF－a水平可作为一项判断AL疗效和预后的临床指标。     

SERUM CHOLESTEROL AND TRIGLYCERIDE LEVELS IN NORWEGIAN ADOLESCENT SCHOOL CHILDREN

ABSTRACT. The frequency distribution of serum cholesterol and triglycerides in 172 boys and 232 girls, 13–16 years, from four elementary schools in Oslo has been determined. The cholesterol values were significantly higher for girls 15–16 years than for boys of the same age group. In the case of triglycerides boys 15–16 years had significantly higher values than boys 13–14 years. Otherwise no statistically significant differences with regard to sex and age were observed. The 85th percentiles have been suggested as appropriate upper normal limits. In all groups the 85th percentile for plasma cholesterol was slightly below 6 mmol/l. The corresponding plasma triglyceride value was below 2 mmol/l.     

BASAL AND HORMONE-INDUCED URINARY CYCLIC AMP IN CHILDREN WITH RENEL DISORDERS

ABSTRACT. The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.     

DNA CONTENT AND PROLIFERATIVE ACTIVITY IN CHILDREN WITH NEUROBLASTOMA

Many studies have reported that neuroblastoma patients with aneuploid DNA content and a low cellular proliferative activity have better outcome; other studies have reported contradictory results. Formalin-fixed, paraffin-embedded archival pretreatment specimens of 56 neuroblastomas were studied. Thick sections from paraffin blocks were deparaffinized, and rehydrated. Following enzymatic digestion and filtration, cellular suspensions were analyzed by flow cytometry. Six tumors were aneuploid (13.3%) and 39 samples were diploid (86.7%). S-phase fraction (SPF) ranged from 1 to 78% with a median of 31%. DNA ploidy and proliferative activity results showed no correlation with the prognostic variables. There was no significant difference between the 5-year overall and event-free survival rates of the aneuploid and the diploid neuroblastomas or between the neuroblastomas with a high and low proliferative activity. The results revealed the prognostic significance of neither DNA ploidy nor the cellular proliferative activity in neuroblastoma in contrast to other studies.     

BASAL AND HORMONE-INDUCED URINARY CYCLIC AMP IN CHILDREN WITH RENAL DISORDERS

Abstract. The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.     

2,3-DIPHOSPHOGLYCERATE LEVELS IN CHILDREN WITH IRON DEFICIENCY ANEMIA AND ACUTE LEUKEMIA

Abstract. Red cell organic phosphates and especially 2,3-diphosphoglycerate (2,3-DPG), lowers the oxygen affinity of hemoglobin (Hb) and shifts the oxygen dissociation curve to the right. Because of the importance of 2,3-DPG (as regulator of the oxygen affinity of Hb), determinations were carried out on: 45 normal children, 7 children with iron deficiency anemia and 35 children with acute lymphoblastic leukemia. In normal children with Hb of 12.69±1.60 g/100 ml, 2,3-DPG was 14.90±0.68 μmoles/g Hb. In children with iron deficiency anemia (Hb 7.94±1.20 g/100 ml), 2,3-DPG was 20.87±3.11 μmoles/g Hb. 2,3-DPG was normal (14.11±0.88 μmoles/g Hb), in 16 patients with acute lymphoblastic leukemia who had never relapsed, while in 19 patients with a history of one or more relapses, 2,3-DPG levels were increased (22.05 ±2.75 μmoles/g Hb). No good explanation may be offered for the high 2,3-DPG levels in these leukemic children.     

VISUAL DISORDERS IN 7-YEAR-OLD CHILDREN WITH AND WITHOUT PREVIOUS VISION SCREENING

ABSTRACT. An analysis of visual defects among 310 children referred from a vision screening of 2178 7-year-old children revealed a 50% frequency of significant eye defects among the referrals (7% of screened children). Of the screened children, one group (1530 children) had previous visual screening three years earlier. The other group (648 children) had no previous vision screening until the age of seven. A comparison between the two groups showed that the risk of finding a new significant eye disorder in a school entrant was more than 6 times greater for a child who was not examined in his preschool years, and the risk of finding an ambiyopic child was more than 10 times greater. The results do indicate the need for continuation of the present vision screening program of pre-school children.     

PRESUMABLY INNATE AND ACQUIRED PROCESSES IN CHILDREN WITH ATTENTION AND/OR READING DISORDERS

Innate and acquired automatic information processing was compared in non-problem students and three groups of educationally troublesome children: two normal reading groups with Attention Deficit Disorder (ADD), one without and one with hyperactivity, and a non-hyperactive Reading Disabled (RD) group. All groups displayed reliable, presumably innate, automatic processing on measures of temporal and frequency sensitivity, but the two ADD groups made less precise judgements than controls. Contrasted with controls, all clinical groups exhibited delayed automatization in arithmetic computation, but the handicapped groups did not differ from controls on other measures of acquired automatization (speed of writing and naming).     

VIRUS SEROLOGY AND SERUM IgE LEVELS IN CHILDREN WITH ASTHMATOID BRONCHITIS

Seventy-two children with wheezing related to respiratory tract infections have been investigated regarding virus serology and serum IgE levels. Positive virus serology with the CF technique was achieved in 18 % to RS virus in spite of absence of epidemics. Seroconversion to ECHO-viruses types 3, 6, 7, 9 and 11 was seen in altogether 18%. Antibody titers indicating infections with parainfluenzavirus, adenovirus or influenza A-2 virus were found less frequently. Twenty-one of the infants had high IgE levels and these infants had allergic heredity, recidivating symptoms, former atopic manifestations and eosinophilia in blood and secretions more often than the infants with normal IgE. Positive virus serology was found as often in the infants with high IgE as in those with normal IgE. Determinations of the serum IgE levels seem to be of value in assessing the possible atopic component in children with asthmatoid bronchitis.     

SERUM LEVELS AND RENAL EXCRETION OF DIGOXIN DURING MAINTENANCE THERAPY IN CHILDREN

ABSTRACT. Iisalo, E. and Dahl, M. (Departments of Pharmacology and Paediatrics, University of Turku, Turku, Finland). Serum Levels and Renal Excretion of Digoxin during Maintenance Therapy in Children. Acta Paediatr Scand, 63: 699, 1974.—To exclude an increased excretion of digoxin as a possible reason for higher dose requirement in children a radioimmunoassay of digoxin in the serum and the 24 hr urine was carried out in 26 children, mainly infants, with congenital heart disease. This procedure was repeated on two consecutive days, in total 64 times during digoxin maintenance therapy.
The daily digoxin dose per kilogram of body weight in these small children was twice as high as that used in adults. The steady state level of serum digoxin corresponded approximately to that of adults. A few fairly high digoxin levels were, however, measured in infants without any signs of digitalis toxicity.
The daily excretion of digoxin in the urine during maintenance therapy was approximately the same in all age groups and on an average 47 per cent of the daily dose. This percentage is somewhat lower than that found in adults. The low renal excretion of digoxin in one newborn caused high serum digoxin levels.
The higher dosage requirement of digoxin per kilogram of body weight in children as compared to adults cannot be explained with differences in the renal excretion of digoxin.     

CLINICAL AND RADIOGRAPHIC RESPONSE IN THREE CHILDREN WITH RECURRENT MALIGNANT CEREBRAL TUMORS WITH HIGH-DOSE TAMOXIFEN

The purpose of this study was to deliver tamoxifen as antiangiogenic therapy to children with recurrent progressive malignant brain tumors. Tamoxifen was administered orally in very high dosage to one child as monotherapy and to two children in combination with oral etoposide and dexamethasone. One boy was diagnosed with high-grade astrocytoma in the brain stem, one girl with anaplastic ependymoma of the fourth ventricule, and one girl with high-grade astrocytoma in the midbrain. Conventional treatment with multiple surgeries, first- and second-line chemotherapy, and external beam therapy had failed. Tumor reduction was seen in radiographic images together with clinical improvement in 2 children, and clinical and radiographic halting of tumor progression was demonstrated in the patient with anaplastic ependymoma. None of the patients developed complications from the treatment. Follow up of the patients ranged from 15 to 30 months with a mean of 17 months. These encouraging preliminary results suggest a potential for this type of therapy. More studies are needed to start clinical trials and prove that angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.     

ARTERIAL BLOOD PRESSURE SERUM LIPIDS AND CARDIOVASCULAR COMPLICATIONS IN FAMILIES OF HYPERTENSIVE CHILDREN

ABSTRACT. The arterial blood pressure (B. P.), the cardiovascular complications and the type of hyperlipoproteinemia were studied in 98 families of hypertensive children (group A) and in 100 families of normotensive children (group B). In group A, hypertension was found in 27% of the parents and 47.4% of grandparents, whereas in group B in 7.5% and 22.5% respectively. In siblings of hypertensive children hypertension was found in 13.5% as apposed to 5.4% of those of normotensive children. Cardiovascular complications were recorded in 27.5% in the parents and grandparents of group A and in 12% in group B. Hyperlipoproteinemia with obvious preponderance of type II (IIa, IIb) and IV was found in 58.5% of parents in group A and 21.1% in group B.     

RELATIONSHIP BETWEEN HAEMOGLOBIN AND SERUM TESTOSTERONE IN NORMAL CHILDREN AND ADOLESCENTS AND IN BOYS WITH DELAYED PUBERTY

ABSTRACT. The concentrations of haemoglobin and of serum testosterone were measured in 215 normal children and adolescents aged 7–20 years, and in 8 boys with constitutional delayed puberty. From the age of 14 years onward haemoglobin and testosterone rose in normal boys and differed significantly from the stable levels observed in prepubertal children and pubertal girls. In the entire series of normal boys ( n = 118, age 7–20 years) concentrations of haemoglobin and testosterone were found to be closely correlated ( r =0.73, p <0.001). These results provide further evidence for a major role of testosterone in the control of erythropoiesis. Therefore, this correlation suggests the use of serum testosterone determination for the proper selection of haemoglobin reference ranges in boys. The respective reference ranges of haemoglobin corresponding to testosterone levels at 0 and 30 nmol/1 were 120.5–148.5 and 143.5–171.5 g/1 (95% confidence limits). Boys with delayed puberty were found to have significantly reduced median values of haemoglobin and testosterone for their chronological age, and 6 of the 8 boys investigated were truly anaemic on this background. Nevertheless, their haemoglobin concentration did appear appropriate as judged from their testosterone levels. This observation supports the idea that the selection of the relevant reference range for haemoglobin in boys should depend on the state of physical development as expressed by serum testosterone.     

THE ROLE OF SERUM FACTORS IN THE LYMPHOCYTE TRANSFORMATION TEST OF CHILDREN WITH ACUTE LEUKAEMIA

ABSTRACT. Révész, T., Szigeti, R. and Schuler, D. (Second Department of Paediatrics, Semmelweis University Medical School, Budapest, Hungary). The role of serum factors in the lymphocyte transformation test of children with acute leukaemia. Acta Paediatr Scand, 63: 715, 1974.—PHA-induced lymphocyte transformation tests were carried out in 14 children who were in full remission of acute lymphoblastic leukaemia and in 12 controls. Stimulation was assessed on the basis of tritiated thymidine uptake. For an adequate testing of lymphocyte reactivity, dose-response curves were established for each child. No significant difference could be observed in either the maximum response, or the shape of the curve, between the leukaemic and the control groups. Supplementation of the culture medium with autologous plasma instead of AB serum did not result in any significant inhibition or stimulation of lymphocyte reactivity to PHA. The lymphocyte response of both leukaemic and control children, however, was greatly reduced when sera from untreated leukaemic children was used. Allogeneic sera drawn from patients in remission exerted little or no inhibitory effect, while that obtained in relapse was again more inhibitory. The observed effect was not due to cytotoxic antibodies, nor due to natural iso-antibodies, but is thought to be a phenomenon closely connected with the active phase of malignant diseases. The exact nature of the agent is still far from being clarified at present.     

CLINICAL FINDINGS AND INTESTINAL IMMUNOGLOBULINS IN CHILDREN WITH PARTIAL IgA DEFICIENCY

Abstract. We studied the intestinal morphology, and the jejunal and rectal immunoglobulins of 16 children with partial IgA deficiency, defined as serum IgA concentration more than two standard deviations below the mean for age, but higher than the lower limit of sensitivity of single radial immunodiffusion (0.02 g/l). Five of the patients had been treated with phenytoin, 2 had juvenile rheumatoid arthritis, 2 had ulcerative colitis and 5 had recurrent upper respiratory tract infections. The jejunal morphology was normal in every case. In 6 cases normalization of serum IgA occurred during the follow-up, while in one patient with ulcerative colitis the concentration fell below 0.02 g/l. In patients with recurrent infections, there was a decreased frequency of infections when the level of serum igA increased. In 4 patients, IgM-containing cells predominated in both the jejunal and rectal mucosa, and IgM was increased in the intestinal juice. In 6 patients a significant increase in IgM-containing cells or a decrease in IgA-containing cells or both were seen in either the rectal or jejunal mucosa. There was no correlation between the number of IgA-containing cells in the intestinal mucosa and the serum level of IgA.