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Background: Acute lymphoblastic leukemia is the most common malignancy in childhood. The survival rate has increased steadily over the last 40 years., Material and Methods: All children aged 0-15 years and diagnosed in Norway in the period 1992-2000, were included in the study (n = 301). The patients were followed up until 1.1. 2005., Results and Interpretation: The diagnosis was made in 301 children, 33 new cases per year (range 24 to 40) on average. The peak incidence was between 2 and 5 years. Four of 6 infants with acute lymphoblastic leukemia and all 4 with mature B-cell leukemia are alive. Two of the remaining 291 children died before treatment was started. 289 were all treated according to the common Nordic NOPHO-ALL 1992 protocol. All children achieved remission (99.7%), except for one who died before remission was achieved. 55 children (19%) relapsed. Radiation to the brain as part of central nervous system prophylaxis was given to just 10% of the children. The 10-year event-free survival (p-EFS) was 76%, and 244 of 289 (84%) were alive 4-13 years after the diagnosis was made. The data are comparable with the best international results.

Background: Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years., Methods: Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided., Results: We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period., Conclusion: Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.

Neurofibromatosis 1 is one of the most common genetic disorders in man. Although almost every body system can be involved, it most frequently affects the skin, the nervous system and the skeleton. Major disease features are café-au-lait spots, axillary/inguinal freckling, neurofibromas and Lisch' nodules. The complications are quite variable, making it impossible to predict the clinical course in an individual patient. To summarize the problems associated with this disease we have quantified manifestations and complications in a group of 38 children with neurofibromatosis 1 who were seen at the University Hospital in Trondheim, Norway between 1987 and 1997. The results are based upon the medical records as well as clinical examination. A wide variety of initial symptoms was recorded, but the majority of the children had café-au-lait spots and axillary/inguinal freckling, two of the seven disease features included in the diagnostic criteria given by the National Institutes of Health. The most frequent complications were tumours, with highest incidence of optic pathway gliomas, disturbances of growth and puberty, delayed psychomotor development and learning disabilities. The risk of complications necessitates regular follow-up in a paediatric department. An annual assessment by an ophthalmologist is also recommended, as well as Visual Evoked Potentials/MRI as screening for optic glioma in children under ten years of age.

Primary intracranial tumours develop in 30-35 Norwegian children each year. Of these tumours, astrocytomas are the most frequent, followed by medulloblastomas, oligoastrocytomas and ependymomas. In this article we give an overview of tumour classification, epidemiology, diagnosis, treatment and prognosis of intracranial tumours in children.

Eighteen of 27 individuals, aged from 6 months to 19 years (mean 5 years, 7 months), from countries in the tropics or the subtropics had either intestinal parasitic infestations or intestinal enteropathogenic bacterial infections or both. Fourteen of those with intestinal pathogens had detectable concentrations of IgE in their fecal extracts, ranging from less than 0.5 to 420 IU/ml extract (mean 33 IU/ml). This rate of occurrence was significantly higher than the number of IgE-positive fecal extracts in a group of 54 healthy nonallergic Norwegian children (p less than 0.001), but did not differ from that of a group of 40 allergic children (p greater than 0.20). The individuals with intestinal helminthic infection had the highest fecal IgE concentrations. Of the 9 individuals who did not have any demonstrable intestinal pathogen, low concentrations of IgE could be detected in feces from only 2, which did not differ from the rate in the healthy Norwegian controls. The concentrations of IgE in the feces of the subjects from tropical/subtropical regions correlated linearly with the corresponding serum concentrations of IgE (r = 0.69; p less than 0.001). The results indicate that the combined load of intestinal pathogens, including helminths, protozoa, and enteropathogenic bacteria, may stimulate IgE production in the gut.

Immunoglobulin E (IgE) was found by a double antibody radioimmunoassay technique (PRIST) in extracts of feces from 21 of 40 children with different kinds of allergy. 15 of the 22 children with gastrointestinal allergy and atopic dermatitis, but only 6 of the 17 patients with hay fever and/or bronchial asthma had detectable IgE in the extracts. The patients with gastrointestinal allergy also had the highest concentrations of fecal IgE, and the concentrations in feces did not correlate with the corresponding serum IgE levels. Furthermore, the presence of IgE in feces correlated with specific IgE antibodies in serum, measured as the sum of RAST classes to the food allergens wheat, fish, cow's milk and egg-white. IgE may therefore have been produced locally in the gut as a result of stimulation by food allergens. Since the concentrations of IgA in feces were also high in many children with allergy, and since some possibility of a positive correlation with high IgE concentration seemed to exist, the stimuli for local production of IgE and IgA may be interrelated.

One hundred fifty-three children with ALL were diagnosed in Norway in the period August 1975-December 1980. One hundred thirty-two of them received 3 infusions of methotrexate as consolidation therapy combined with methotrexate intrathecally as CNS prophylaxis. Eleven (44%) of the total 25 methotrexate cases with WBC above 50 X 10(9)/L were in CCR after 4 1/2-10 years. Two more cases had discontinued therapy, while in second remission. The event-free survival of all diagnosed 32 children in Norway with WBC above 50 X 10(9)/L was 37%. Seven infants below the age of 1 year are included in the 32 cases.

The gel filtration profile of immunoglobulin E (IgE) in extracts of feces from 2 children was compared with IgE myeloma protein which had been exposed to proteolytic digestion by chymotrypsin. The peak of the chymotrypsin-digested IgE myeloma protein was found to be similar to that of fecal IgE after an elution volume between those of albumin and myoglobin, corresponding to a molecular weight of approximately 40,000 daltons. In the fractions where the peak of fecal IgE was found, no evidence for the presence of specific IgE antibodies (measured by RAST) could be detected. Fecal IgE could be purified by using an immunosorbent column to which rabbit antihuman IgE was coupled. Sufficient amounts of fecal IgE could thus be obtained and used in autoradiographic experiments. The IgE-containing fractions could also be detected with 125I-labelled second antibodies to visualize the IgE precipitates.

Sixty-one children were examined for thyroid dysfunction as an adverse late effect after cessation of antileukemic treatment. The aim of the study was to contribute to clarifying which types of therapy can cause this endocrine disorder. Our treatment protocols do not include cranial irradiation as CNS prophylaxis, but we give relatively intensive intrathecal methotrexate treatment. The results indicate that this cytostatic regimen alone does not cause thyroid dysfunction as an adverse late effect.

The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 7 1/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (less than 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations, while the others maintained 1,25-(OH)2D levels within normal limits. 24,25-(OH)2D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phosphatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.

Immunoglobulin E (IgE) in human feces was characterized by radioimmunoassays with different specificities of the second antibodies, and by immunoprecipitation techniques. The fecal IgE was compared with an intact IgE myeloma protein and with Fc'' fragments of the IgE molecules, obtained after prolonged chymotrypsin-digestion of the IgE myeloma protein. The experiments showed that both the fecal IgE and Fc'' fragments shared the D epsilon 1 antigenic determinants while the intact IgE had both D epsilon 1 and D epsilon 2 determinants. They also shared thermal stability at 56 degrees C as compared to intact IgE. Fecal IgE and Fc'' fragments both showed rapid anodal migration in an electric field, different to that of intact IgE. A tandem crossed immunoelectrophoresis technique provided signs of immunological identity between the precipitates of fecal IgE and those of the Fc'' fragments. It is therefore likely that most, if not all, IgE in human feces consists of Fc" fragments.

Loops of small intestine in seven rabbits were resected with intact pedicle and ligated at both ends after instillation of 0.5 ml of Gastrografin, Urografin 76%, Amipaque 370 mg I/ml, Amipaque 170 mg I/ml or physiologic saline. After half an hour, the amount of fluid in the loops containing Gastrografin and Urografin 76% increases about twice as much as in the loops containing Amipague with the same iodine concentration because of their greater osmolality. The differences between the loops with isotonic Amipaque (170 mg I/ml) and physiologic saline are not significant. Precipitation occurs when sodium and meglumine salts of diatrizoate, metrizoate, iothalamate, iocarmate and ioglycamate are mixed with 0.05 N HCl. No precipitation occurs with Amipaque, not even when the HCl concentration is as high as 1.2 N. Precipitation occurs when Gastrografin is added to gastric juices with low pH, but is not seen with Amipaque should be a suitable contrast medium for gastrointestinal examinations because of its low osmolality and toxicity and good solubility in gastric juice.

In this study we looked for the occurrence of immunoglobulin E (IgE) in feces from healthy individuals and determined the total daily excretion and day-to-day variation in IgE in feces from patients with allergy, as well as the correlation between concentrations of IgE in small samples of feces and the total amounts of IgE in feces collected over a longer period. Concentrations of IgE in extracts of small samples of dry feces correlated well with the total daily amounts of IgE in feces collected over a 3-day period. Thus, single small samples of feces can be used to measure the excretion of IgE with feces at that time. In 3 children, studied over a 5-week period, the IgE excretion varied somewhat from one day to another, but was largely within a certain range of concentrations. Addition of trypsin inhibitor to fresh feces had no influence on the IgE concentrations of the resulting fecal extracts. Less than 10% of 88 presumably healthy infants, children, and adults had detectable IgE in their feces, while 21 of 40 children with various kinds of allergy had measurable fecal IgE. Only 3 of 13 individuals who were suffering from infectious acute gastroenteritis had IgE-positive fecal extracts. This was also the case for 6 of 25 adult patients in clinical remission of ulcerative colitis or Crohn's disease. Seven of 14 adult patients with chronic pancreatitis had measurable IgE in feces, and the concentrations were up to ten times the upper limit of IgE found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoglobulin E (IgE) was demonstrated by a double antibody radioimmunoassay technique (PRIST) in 5 of 17 unconcentrated fecal extracts from children. Four of the PRIST-positive extracts also had measurable levels of IgE determined by an enzyme-linked immunosorbent test (Enzygnost IgE). However, using a competitive antibody radioimmunoassay technique (RIST), IgE was found in all unconcentrated fecal extracts. The RIST-IgE levels of the extracts were higher and did not correlate to IgE measured by the other methods, nor to the IgE in serum from the same children or to the manifestation of allergy. On the other hand, 4 of the 5 children with measurable PRIST-IgE levels, and 3 of the 4 children with detectable Enzygnost IgE concentrations in the extracts, had elevated serum IgE as well as a history of allergy. Gel filtration studies indicated that IgE determined by the PRIST and Enzygnost IgE methods had been degraded to fragments of lower molecular weight than that of albumin. This study also suggests that the IgE in feces measured by the RIST method is overestimated due to the influence from nonspecific substances of high molecular weight.

Five of 6 fecal extracts from small children with intestinal Ascaris lumbricoides infection were IgE-positive before antiparasitic treatment with mebendazole was given. After treatment one patient still showed high fecal IgE level, but the samples from the remaining children showed either undetectable IgE values, or values just above the limit of detection. The serum IgE concentrations, however, decreased more slowly than the fecal IgE levels did. In the child with persistent high fecal IgE level after therapy, ova from Hymenolepis nana could still be found in feces, although the A. lumbricoides infection had been successfully treated. Gel filtration studies showed that fecal IgE from a patient with the parasitic infection was degraded to fragments corresponding to a molecular weight of approximately 40,000 daltons, similar to that of fecal IgE from a patient with gastrointestinal allergy. The number of IgE-positive fecal extracts in those patients before antiparasitic treatment was given differed significantly from the number of positive fecal IgE extracts from healthy nonallergic children (p less than 0.01), but not from children with different kinds of allergy (p greater than 0.20). The fecal IgA concentrations were not different before and after antiparasitic therapy. The finding of IgE in feces from individuals with intestinal ascaris infection and nearly complete disappearance of IgE in feces after successful therapy is further evidence of local production of IgE in the gut mucosa.

We have measured MTX and 7-OH-MTX in plasma and urine samples from a 9-year-old boy treated with six consecutive 24-h IV high-dose MTX courses (33.6 g/m2) after a relapse of ALL. The between-course pharmacokinetics of MTX and 7-OH-MTX were found to be highly reproducible. Both MTX and 7-OH-MTX elimination followed a biphasic curve, initial half-lives (t1/2(alpha] being 2.86 +/- 0.44 h and 5.14 +/- 0.46 h (mean +/- SD) and second-phase biological half-lives (t1/2(beta] being approximately 18 and 16 h, respectively. The apparent volume of distribution for MTX was 0.8 L/kg, whereas the corresponding value for 7-OH-MTX was threefold less. Since clearance of MTX was within the range reported for lower doses, the data suggest that MTX pharmacokinetics are not dose-dependent up to 33.6 g/m2.

Five children, ages 2.5 to 12 years (mean 6.2 years), with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were given 22 courses of high-dose methotrexate (HD-MTX) therapy (6-8 g/m2/24 h). No serious clinical complications were encountered, but stomatitis occurred after three (14%) of the courses. First-phase elimination half-lives (t1/2(alpha)) of MTX and 7-hydroxy-methotrexate (7-OH-MTX) after 21 infusions were 2.7 +/- 0.4 h and 6.5 +/- 1.8 h (mean +/- SD). In one course (4.5%) there was delayed systemic MTX elimination, with first-phase elimination half-lives (t1/2(alpha] for MTX and 7-OH-MTX of 4.2 and 9.9 h, respectively, and second-phase elimination half-lives (t1/2(beta)) of 43 and 58 h. Significant decreases in white blood cell count, increases in serum creatinine, and increases in alanine aminotransferase and/or aspartate aminotransferase during the first 2-6 days were present in five (23%), three (14%), and six (27%) of the courses, respectively. The regimen was tolerated well by the children.

The pilot study using HDM in all cases of ALL in childhood had been run for 4 1/2 years as of September 1985. Fourteen (23%) of all 62 diagnosed cases of ALL had WBC above 50 X 10(9)/L, all 14 achieved CR. Three of them were below one year of age, two also had WBC above 400 X 10(9)/L, the third infant had B-cell-leukemia. The remaining 11 children received our new HDM protocol (Fig. 1), one of them had relapsed (BM) as of September 1985.

We recently developed enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-BK virus IgG- and IgM-antibodies, and also a convenient and rapid serum neutralization test. Complemented by a traditional haemagglutination inhibition test (HAI) these methods were used to investigate the longitudinal response to BKV infection in sequentially taken sera from 29 children under treatment for cancer. In separate experiments it was shown that the results were not at any extent influenced by antibodies against other polyomaviruses. At the time of diagnosis the prevalence of specific IgG- and IgM-antibodies and the geometric mean IgG levels were not significantly different for the patients compared with a group of healthy children. The primary infections seemed to occur at the same age for the two groups of children. Seven of the patients had a primary infection with BKV. The results indicate that the host response in moderately immunosuppressed children during primary infection is the same as expected for healthy individuals with the development of specific IgG, HAI, and NT antibodies, and, usually, production of BKV-IgM for several months. The results indicated that whether specific IgM was demonstrated in the first sample or appeared later during a reactivation episode, this parameter was correlated with profound immunosuppression. Significant titre changes, detectable IgM antibodies and/or seroconversions were demonstrated in 69% (20/29) of the cancer patients. Such indications of recent viral activity was recorded in 42% (8/19) of children with meningococcal infections. The observation periods for the two groups of patients are, however, not directly comparable.

A seven-year-old boy had cardiac symptoms for five months before the diagnosis of Wilms tumor was made. The tumor extended into the inferior vena cava through the renal vein and protruded into the right atrium. All demonstrable tumor masses could be removed at a one-step surgical procedure without using cardiopulmonary bypass. Intensive postoperative chemotherapy has been given, and 15 months after surgery he was without signs of relapse.

Nineteen children treated for Wilms' tumor (thirteen cases) or Hodgkin's disease (six cases) with cytostatic agents and/or radiotherapy were studied cytogenetically on lymphocytes cultivated from blood samples drawn after at least 1 year of complete remission after end of therapy. A reference group of children was matched for age, sex, and residence. The frequencies of sister chromatid exchange (5.4 versus 5.6 SCE/cell), and chromosome damage type gaps (6.6 versus 7.1%) and breaks (1.9 versus 1.9%) were not different in the two groups, but exchange type aberrations were more frequent in the patients (0.9 versus 0.06%). Fifty karyotypes were analyzed in all but two cases of Hodgkin's disease. The overall frequency of stable (3.1 versus 3.8%) and unstable (1.7 versus 1.4%) structural chromosome changes such as translocations, deletions, chromatid exchanges, and dicentrics were not different in the patient and the control groups. If the chromosome data reflect a general cancer risk, this risk cannot be considerably higher among the cancer-treated children.

In this study plasma concentrations of lactoferrin (LF) and C-reactive protein (CRP) are examined in 9 children with different kinds of cancer but without any intercurrent infections. New, sensitive enzyme-linked immunosorbent assay for LF and CRP are described. The samples are drawn before, during, and after the cytotoxic drugs are given. The cytotoxic courses include cis-platinum, vincristine, adriamycin, cytarabine, and methotrexate (6 g/m2/24 h and 33.6 g/m2/24 h). During the infusion of methotrexate 33.6 g/m2 the concentrations of LF are increased, only a small increase of CRP is observed, and for the other groups there is no changes of both parameters.

Neurofibromatosis takes two major forms; classical or peripheral neurofibromatosis as described by von Recklinghausen, which accounts for more than 90% of the cases, and central or bilateral acoustic neurofibromatosis. The diagnosis is often postponed until adulthood, since the classical signs gradually appear during childhood and adolescence. It is a relatively common autosomal dominant disorder affecting about one in 3,000. At least 20% of patients will develop one or more complications associated with neurofibromatosis. One of the complications is the development of malignancies. Four children at our hospital developed different forms of malignant tumours arising from neurofibromatosis. We recommend that all patients suffering from this disease are evaluated in detail after the diagnosis has been confirmed and are followed up every six to 12 months. In this way complications may be discovered early and the necessary steps taken.