Neurofibromatosis presenting with a cherubism phenotype.

We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1.

PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial.

BACKGROUND: Recently, polyethylene glycol (PEG 3350) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation. However, no large randomised controlled trials exist evaluating the efficacy of either laxative. AIMS: To compare PEG 3350 (Transipeg: polyethylene glycol with electrolytes) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects. PATIENTS: One hundred patients (aged 6 months-15 years) with paediatric constipation were included in an eight week double blinded, randomised, controlled trial. METHODS: After faecal disimpaction, patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6 g/sachet) while children > or =6 years started with 2 sachets/day. Primary outcome measures were: defecation and encopresis frequency/week and successful treatment after eight weeks. Success was defined as a defecation frequency > or =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were side effects after eight weeks of treatment. RESULTS: A total of 91 patients (49 male) completed the study. A significant increase in defecation frequency (PEG 3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week; lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success was significantly higher in the PEG group (56%) compared with the lactulose group (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at defecation than children using lactulose. However, bad taste was reported significantly more often in the PEG group. CONCLUSIONS: PEG 3350 (0.26 (0.11) g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate with fewer side effects. PEG 3350 should be the laxative of first choice in childhood constipation.

[A teenager presenting with vomiting, general malaise and weight loss]. / Een tiener met braken, algehele malaise en gewichtsverlies.

A 16-year-old girl had symptoms of vomiting, malaise and weight loss for two months. Blood tests revealed an elevated activity of liver enzymes and hyperthyroidism. Although the patient at first denied the possibility of pregnancy, a pregnancy was subsequently confirmed. Hyperemesis gravidarum was diagnosed based on the combination of the clinical symptoms, pregnancy and increased serum human chorionic gonadotrophin and oestradiol. Hyperemesis gravidarum also explained the demonstrated biochemical hyperthyroidism and elevated liver enzyme levels. Rapid alleviation of all the clinical symptoms was seen after termination of this unwanted pregnancy. Although vomiting, malaise and weight loss in children can have many different causes, in girls at a sexually mature age a pregnancy with possible hyperemesis gravidarum should certainly also be considered and a gynaecological examination performed.

[Fulminating pneumococcal septicemia in a 2 year old child with sickle cell anemia]. / Fulminant verlopende pneumokokkensepsis bij een 2-jarig kind met sikkelcelanemie.

A 2-year-old boy known with homozygous sickle cell anaemia became acutely ill at home. Despite intensive care, he died a few hours later due to pneumococcal septicaemia. In young children with homozygous sickle cell anaemia, spleen function is already severely impaired in childhood due to haemolysis and frequent vaso-occlusive episodes. These children therefore have an elevated susceptibility to severe invasive infections with encapsulated bacteria. Vaccination against pneumococci at-2 years of age, re-vaccination every 3-5 years, and antibiotic prophylaxis until 5 years of age, and thereafter with possible infections, are therefore necessary.

Comparative bioavailability of rectal and oral formulations of chloroquine.

The relative bioavailability of chloroquinone in Witepsol H15 suppositories can vary between 10 and 53% of the bioavailability of a tablet formulation in adults. Therefore, it is therapeutically not sound to replace chloroquine tablets by a rectal formulation with the same dose.

Motility of leukemic cells in collagen gel related to immunological phenotype in childhood acute lymphoblastic leukemia.

Motility of leukemic cells was measured in a three-dimensional collagen matrix assay. Leukemic cells from 16 children with acute lymphoblastic leukemia (ALL) and normal peripheral blood lymphocytes (NPBL) from 6 healthy volunteers, were allowed to migrate into this collagen matrix for 48 h at 37 degrees C. NPBL migrated much further (300-600 micron) than leukemic cells (0-200 micron). Among the leukemic cases, only common ALL and one case of null ALL showed some migration (0-200 micron). T-All cells did not migrate at all under the circumstances of this experiment.

Capping of leukemic cells with monoclonal anti-HLA-A,B,C related to prognosis in childhood acute lymphoblastic leukemia.

Capping of leukemic cells with a monoclonal antibody against HLA A,B,C determinants was studied in 53 cases of childhood acute lymphoblastic leukemia (ALL). Determination of the percentages of capped cells after different times of incubation with anti-HLA A,B,C show that T ALL and common ALL do have quite different kinetics of HLA capping. In T ALL all cases reach levels of percentage of capped cells above 30%, in common ALL only 11 of 31 cases cap well. Dilution of the antiserum in 6 common ALL cases results in an increase of capped cells, but the original kinetics of the common ALL capping remain. ALL cases with capping curves above 30% have a worse prognosis (shorter continuous complete remission) than cases with capping curves below 30% in the total group as well as in the non-high-risk group.

Peanut agglutinin, a marker for T-cell acute lymphoblastic leukemia with a good prognosis.

Peanut agglutinin (PNA) binding was studied in cells from 74 children with acute lymphoblastic leukemia (ALL). PNA positivity occurred in 50% of T-ALL (12 of 24) and was rare in other types of ALL. There was no clear relationship between PNA and initial white blood cell count, French-American-British classification, stage of differentiation of leukemic cells, hand mirror cells, and organomegaly at diagnosis. Prognosis, however, was significantly better (continuous complete remission, death) in the PNA-positive T-ALLs. It seems that PNA is a useful marker for a subgroup of T-ALL with a better prognosis.

Prognostic value of 5'nucleotidase in acute lymphoblastic leukemia with the common-ALL phenotype.

5'-Nucleotidase (5'NT) is an enzyme found on the surface membrane of leukemic cells with the c-ALL phenotype. We studied 79 children with acute lymphoblastic leukemia (ALL). Thirty six of them had the c-ALL phenotype. Within this c-ALL group, ten had 5'-NT positive leukemic cells. Clinical data were available in 33 c-ALL cases. Sex, age and initial white blood cell count were comparable between 5'NT positive and 5'NT negative c-ALL cases. In the 5'NT positive group the probability of complete continuous remission was significantly lower than in the 5'NT negative group (p less than 0.05).

Significance of number of HLA determinants in HLA capping in childhood acute lymphoblastic leukemia.

The density of HLA determinants on the cell surface was studied in relation to HLA capping in childhood acute lymphoblastic leukemia (ALL). Analysis was performed with flow cytometry (FACS) and a subjective labeling score. These two methods gave comparable results. In T-ALL high percentages of capped cells were related to low numbers of HLA determinants. In c-ALL we found the opposite. This study shows that capping capacity and number of HLA determinants in childhood ALL are inversely related.

Handmirror cells in childhood acute lymphoblastic leukemia related to immunological phenotype.

In 96 cases of childhood acute lymphoblastic leukemia (ALL), handmirror cells (HMCs) were counted in cytospin preparations of washed lymphoblasts obtained at diagnosis. HMC counts were significantly lower in T-ALL as compared to C-ALL (p less than 0.001). In T-ALL and pre-T-ALL 2/35 cases had more than 10% HMCs; in C-ALL 22/41 cases had more than 10% HMCs. In two cases of B-ALL 19% and 36% HMCs were found. Thus, HMC expression in ALL is related to the immunological phenotype, especially found in ALLs originating along the B-cell lineage.

Handmirror cells and central nervous system relapse in childhood acute lymphoblastic leukaemia.

In 53 children with acute lymphoblastic leukaemia (ALL), initial handmirror cell (HMC) count among lymphoblasts was studied in relation to the occurrence of a relapse in the central nervous system (CNS), taking into account the white blood cell count (WBC) and the immunological phenotype. The children were followed for a period limited by (1) the first CNS relapse, (2) death or (3) the closing day of this study. The median follow-up period was 30 months, range 2-106 months. HMC counts were available in bone marrow smears of 41 children and in cytospins of 35 children. Cytospins proved to give more reliable and consistent results than bone marrow smears. In the 35 'cytospin' children no CNS relapses occurred in the group of 16 children with non-T-non-B-ALL and HMC counts above 10%. However, in the group of 10 children with non-T-non-B-ALL and HMC counts below 10%, and in the group of 9 children with T-ALL (HMC less than or equal to 11%), 6 and 5, respectively, got a CNS relapse. The CNS relapse-free period was not significantly different between these last two groups, whereas both groups did differ significantly from the group mentioned first (p less than 0.01). This was not found in bone marrow smears of 41 children, presumably because of the inaccurate counting results. A low initial HMC count in cytospins is associated with an increased risk for the occurrence of a CNS relapse in children with ALL. This prognostic factor seems to be independent of other prognostic signs such as immunological phenotype and high WBC.

Differences in capping behavior between immunological phenotypes in childhood acute lymphoblastic leukemia. A study with ConA and an anti-HLA-ABC backbone.

Capping with concanavalin A (ConA) and monoclonal anti-HLA-ABC backbone was studied in childhood acute lymphoblastic leukemia (ALL). Capping with ConA and HLA gave quite different results, both in common ALL and T-ALL. With ConA most cases capped poorly, comparable to results described in chronic lymphatic leukemia and lymphoma, but in several cases capping was comparable to that of normal lymphocytes. In HLA capping T-ALL cells capped better than common ALL cells. HLA capping of T-ALL cells is comparable to that of normal lymphocytes. HLA capping results in handmirror cell formation giving support to the hypothesis that capping and motility are associated events.

[Chyloperitoneum in newborn infants]. / Chyloperitoneum bij de pasgeborene.

The authors describe a newborn, in which a diagnosis of ascites was made before birth by ultrasound. Ascites without other signs of hydrops may be caused by meconium-peritonitis, perforation of the bile ducts, disorders of the portal or systemic circulation, flow disturbances in the lymphatic vessels, urinary obstruction or a ruptured ovarian cyst. In this case there was a chylous ascites in a child with Down's syndrome. Diagnosis, pathogenesis and treatment are discussed. With conservative treatment the child was free of symptoms at the age of 6 months.