Svein Kolmannskog

Immune thrombocytopenic purpura in childhood in Norway: a prospective, population-based registration.

A prospective, population-based registration of children with immune thrombocytopenic purpura (ITP) was performed in Norway in 1996 and 1997. Ninety-two cases were identified, indicating an incidence of 5.3 per 100,000 children under 15 years. The sex ratio (female/male) was 1.2/1. Fifty six percent presented with cutaneous signs only. The lowest platelet count was < 20x109

Pharmacokinetics of Methotrexate and 7-Hydroxy-Methotrexate after High-Dose (33.6 g/m2) Methotrexate Therapy

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.

Thyroid Function in Children after Cytostatic Treatment for Acute Leukemia

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 Excretion of IgE with Feces from Healthy Individuals and from Others with Allergy and Diseases Affecting the Intestinal Tract

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 Crohns 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)

High-Dose Methotrexate Therapy (6‐8 G/M2) in Childhood Malignancies: Clinical Tolerability and Pharmacokinetics

Five children, ages 2.5 to 12 years (mean 6.2 years), with acute lymphoblastic leukemia or non-Hodgkins 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.

Lactoferrin and C-Reactive Protein in Response to Cytostatic Drugs with Emphasis on Methotrexate

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.

Immunoglobulin E in Extracts of Feces from Children

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.

Fragments of IgE Antibodies in Human Feces

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.

Immunoglobulin E in Feces of Children with Intestinal Ascaris lumbricoides Infestation

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.

Detection of immunoglobulin E in feces by immunoprecipitation, and characterization of associated non-immunoglobulin precipitins.

All concentrated human fecal extracts tested formed precipitates in double immunodiffusion with goat antiserum to IgE, as well as with normal goat sera. However, no such precipitates were formed by fecal extracts and rabbit sera. IgE precipitates obtained with both goat and rabbit antisera to IgE showed reactions of non-identity with the former precipitates which seemed to represent complexes of trypsin or chymotrypsin in feces and an alpha-protein in goat sera. This alpha-protein, which was responsible for the non-immunoglobulin precipitations, was different from human alpha 1-antitrypsin. The trypsin-like components in feces had low molecular weights, and might represent degradation products of trypsin or chymotrypsin. After using a second labelled antiserum, precipitates between rabbit antiserum to IgE and extracts of feces could be visualized by means of autoradiography. They were seen in fecal extracts in which IgE could also be determined by a double-antibody paper radioimmunoassay technique (paper radio immunosorbent test; PRIST). Since the concentrations measured by a radioactive single-radial immunodiffusion method correlated to some extent with the PRIST concentrations, the latter precipitates were likely to represent IgE in feces.