Oral calcium phosphate: a new therapy for Crigler-Najjar disease?

BACKGROUND & AIMS: Calcium phosphate binds unconjugated bilirubin in vitro, and dietary calcium phosphate supplementation reduces the serum bilirubin level in rats with hereditary unconjugated hyperbilirubinemia (Gunn rats). The aim of this study was to evaluate the effect of oral calcium phosphate supplementation on plasma bilirubin levels in patients with Crigler-Najjar disease. METHODS: A placebo-controlled, double-blind, crossover design was used. Eleven patients, 2-42 years of age, participated. The group included 5 patients with type I disease who were all treated with phototherapy and 6 patients with type II disease who were primarily treated with phenobarbital. In addition to plasma bilirubin levels, dietary intake and urinary and fecal excretion of calcium and phosphate were evaluated. RESULTS: A modest but significant decrease in serum bilirubin was observed in patients with type I disease (18% +/- 6%, P = 0.03) but not in patients with type II disease during treatment with calcium phosphate. Urinary output of calcium and phosphate did not change during the treatment period. CONCLUSIONS: Oral calcium phosphate may be a useful adjuvant to photo-therapy in Crigler-Najjar type I disease.

Small influence of parental educational level on the survival of children with leukaemia in The Netherlands between 1973 and 1979.

We studied the effect of parental educational level (PEL), an indicator of socio-economic status (SES), on survival of children with acute lymphoblastic (ALL) and non-lymphoblastic leukaemia (ANLL). All children with ALL and ANLL diagnosed in The Netherlands in the period 1973-1979, registered by the Dutch Childhood Leukaemia Study Group and followed until 1991 were included. Bone marrow and blood smears had been uniformly classified in a central laboratory; cases with acute lymphoblastic leukaemia (ALL) were subdivided into standard risk (SR) and high risk (HR). PEL, assessed as a risk indicator in a separately conducted population-based case-control study of the same children (response rate: 88%), was divided into low, when neither of the parents had more than elementary school or lower vocational education, and high when either had more. Children with SR ALL of high PEL parents had a slightly higher 10-year survival rate than of low PEL parents (58% versus 54%, P = 0.25), whereas survival for the latter increased more (P = 0.06) from a lower level in the period 1973-1975. However, children of low PEL parents with HR ALL and ANLL had a higher 10-year survival rate compared with children of high PEL parents (P = 0.10 and 0.22, respectively). Children without information on PEL, non-responders, migrants and with missing values exhibited slightly worse survival rates. The influence of PEL on survival of acute leukaemia in children in The Netherlands during 1973-1979 appeared small or even equivocal. Small differences in SES and optimal geographic and financial access to care, delivered through national treatment protocols, may be responsible for these results.

The role of serum thyroglobulin concentration and thyroid ultrasound imaging in the detection of iodide transport defects in infants.

When discovered by neonatal screening, a thyroid dyshormonogenesis is usually not recognized as a goitre. Especially a total iodide transport defect can easily be misclassified as thyroid agenesis, since radionuclide imaging cannot visualize the thyroid. We present the only iodide transport defect ever discovered in the Netherlands, the 35th reported in the literature, and the first one found exclusively as a result of neonatal screening. We demonstrate that iodide transport defects, in common with organification and deiodinase defects, can be distinguished from thyroid dysgenesis by demonstrating a normal or enlarged thyroid ultrasound image, and especially by measuring very high serum thyroglobulin levels (above 1000 pmol/l). In the presented case, an iodide-123 saliva-to-serum ratio near unity completed the etiologic classification. Measurement of serum thyroglobulin levels, in combination with thyroid ultrasound imaging, will improve the early identification of hereditary types of congenital hypothyroidism, and especially iodide transport defects, in patients found by neonatal thyroid screening.

Malignant lymphomas in children in The Netherlands in the period 1973-1985: incidence in relation to leukemia: a report from the Dutch Childhood Leukemia Study Group.

A retrospective study was done of the incidence of non-Hodgkin's lymphoma (NHL) in children in the Netherlands in the period 1973-85 in relation to that of acute lymphoblastic leukemia (ALL). Complete ascertainment of cases was most likely achieved through the network of cooperating pediatricians of the Dutch Childhood Leukemia Study Group (DCLSG). The incidence of NHL remained constant at 0.75 per 10(5) children per year; the boy/girl ratio was 2.5. In +/- 25% of cases the disease was localized at diagnosis. Of children with NHL who were not listed in the DCLSG leukemia register, 19% had greater than or equal to 25% lymphoblasts in the bone marrow at diagnosis, representing an overlap with ALL of +/- 5%. In 1% of the children with NHL an immuno-deficiency disorder preceded the diagnosis. The incidence of Hodgkin's disease (HD) was 0.3 per 10(5) children per year, with some fluctuation over time, the peak being 0.7 in 1983. The boy/girl ratio was 2.7. Age-specific incidence rates, clinical features of NHL and HD, as well as the ALL to NHL ratio corresponded with those in other European countries and for white children in the USA.

Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation.

We report on two male and two female relatives with intestinal lymphangiectasia; severe lymphedema of limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation. Main facial anomalies are a flat face, flat nasal bridge, hypertelorism, small mouth, tooth anomalies, and ear defects. Their parents are consanguineous. This disorder probably is an hitherto undescribed autosomal recessive syndrome.

Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V). A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG).

The Dutch Childhood Leukemia Study Group (DCLSG) performed a phase III study-Study (ALL) V-to evaluate the effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for children (0-15 years) with standard risk acute lymphoblastic leukemia (ALL) (white blood cell [WBC] counts less than 50.10(9)/L, absence of mediastinal mass, and/or cerebromeningeal leukemia). Furthermore, the influence of initial patient and disease characteristics on the outcome was analyzed. Between May 1979 and December 1982, 240 patients entered the study and were randomized into two groups: group A (n = 122) received induction treatment with vincristine (VCR), prednisone (Pred), and L-asparaginase (L-Asp); for group B (n = 118), induction therapy consisted of VCR, Pred, L-Asp, and rubidomycin (Rub). All patients subsequently underwent cranial irradiation (doses adjusted to age) in combination with intrathecal methotrexate; maintenance therapy of 6-mercaptopurine and methotrexate for 5 weeks followed by vincristine and prednisone for 2 weeks was given for 24 months. The complete remission (CR) rate was similar in both groups (94.5%). Event-free survival (EFS) 5 years after diagnosis was higher in group B (62.5 +/- 4.5%) than in group A (54.7 +/- 4.5%), although the difference is not significant (p = 0.20). A high initial WBC (greater than or equal to 10.10(9)/L), age (greater than or equal to 10 years), a low platelet count (less than 100.10(9)/L), and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.05). Sex, French-American-British (FAB) classification group, immunophenotype, and treatment in specialized centers did not have a significant impact on event-free survival.

[Results of treatment of children with acute lymphatic leukemia (ALL) according to the ALL V protocol of the Netherlands Working Group on Leukemia in Children]. / Resultaten van behandeling van kinderen met acute lymfatische leukemie (ALL) volgens SNWLK protocol ALL V.

The Dutch Childhood Leukemia Study Group performed a phase III study (Study ALL V) to evaluate the effectiveness of addition of rubidomycin to induction treatment with vincristine, prednisone and L-asparaginase in children (0-15 years) with standard risk acute lymphoblastic leukemia: WBC less than 50.10(9)/l, absence of mediastinal mass and/or cerebromeningeal leukemia. Furthermore, the influence of some initial patient- en disease-characteristics on the outcome was analysed. Between May 1979 and December 1982 240 patients entered into the study and were randomized into 2 groups: group A (n = 122) received induction treatment with vincristine, prednisone and L-asparaginase; group B (n = 118) received induction treatment with vincristine, prednisone, L-asparaginase and rubidomycin. All patients received cranial irradiation (doses adjusted to age) and intrathecal methotrexate, followed by maintenance treatment with 6-mercaptopurine and methotrexate for 5 weeks, alternated with vincristine and prednisone for 2 weeks, up to 24 months. Complete remission rate was 94% in both groups. Event-free survival at 5 years after diagnosis was higher in group B (62% +/- 4.6%) than in group A (54.2% +/- 4.6%) but the difference was not significant. A higher initial WBC, age greater than or equal to 10 years and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.01). Sex, FAB-morphology, immunophenotype and place of treatment (center or general hospital) were not significant factors.