[The determinant role of an accurate medicosocial approach in the prognosis of pediatric blood diseases]. / Rôle déterminant de la prise en charge médicosociale dans le pronostic des affections hématologiques de l'enfant.

The care of infancy and childhood blood diseases implies a comprehensive medicosocial approach. This is a prerequisite for regular follow-up, for satisfactory compliance to treatment and for optimal patient's quality of life. Different modalities of medicosocial approach have been developed in the pediatric department (firstly in the Hospital Saint Pierre and than in the Children's University Hospital HUDERF). The drastic importance of a recent reform of the increased family allowances is briefly presented. The author underlines the determinant role of an accurate global approach, in which the patient and the family are surrounded by a multidisciplinary team, including social workers.

[Prevention of hemoglobinopathies in Brussels: a necessity?]. / Prévention des hémoglobinopathies à Bruxelles: une nécessité?

Haemoglobinopathies are the most frequent genetic diseases in the world. The estimated frequency of carriers in the world is of 200 millions while there is about 300.000 births per year of major forms of haemoglobinopathies. The neonatal screening of haemoglobinopathies performed at the Hospital Erasme on around 80% of births in Brussels since 1994 has demonstrated that the frequency of carriers of an abnormal haemoglobin is around 1.5% while more than 1/2.000 newborns has a major haemoglobinopathy. A strategy must be adopted to manage the haemoglobinopathies in Brussels.

Five years of experience with hydroxyurea in children and young adults with sickle cell disease.

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P =.0002) and days in the hospital (P <.01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support. (Blood. 2001;97:3628-3632)

Antisickling activity of sodium cromoglicate in sickle-cell disease.

Two groups of patients with sickle-cell disease were given a single dose of sodium cromoglicate by inhalation or nasal route. The striking decrease in sickle cells after treatment by both routes lends support to the role of sodium cromoglicate in sickle-cell disease treatment.

In vitro antisickling activity of a rearranged limonoid isolated from Khaya senegalensis.

We previously observed that aqueous extracts of the stem bark and leaves of Khaya senegalensis exhibited a strong antisickling activity. These results prompted us to find out the constituent(s) responsible for these properties using an in vitro bio-guided fractionation. The bioassay was based on sickle cells countings, before and after deoxygenation, in blood samples taken from patients with severe sickle cell anemia and pre-incubated with the drugs to be tested. The main active constituent was identified as a rearranged limonoid whose structure was recently elucidated. In comparison with pentoxifylline used as standard, the in vitro antisickling activity of this limonoid was much higher at any concentrations and incubation conditions. In addition, it did not alter significantly the corpuscular indices.

In vitro antisickling activity of cromolyn sodium.

The improvement in sickle cell disease (SCD) children receiving cromolyn sodium therapy prompted us to investigate its antisickling activity in vitro. The number of sickle cells was determined in deoxygenated blood samples from 15 children with severe SCD. At the eight concentrations tested, cromolyn sodium exhibited a significantly higher activity than pentoxifylline, the standard compound. Therefore cromolyn sodium would appear to be an interesting candidate for SCD therapy and deserves further in vivo investigations.

Growth failure, encephalopathy, and endocrine dysfunctions in two siblings, one with 5-oxoprolinase deficiency.

UNLABELLED: Two female siblings, born to consanguineous parents, presented with a similar phenotype characterized by severe growth and developmental failure, dysmorphic features, thyroid and gonadal dysfunction, autistic traits and hand stereotypes resembling Rett syndrome. In the elder patient, analysis of urinary organic acids disclosed a very high excretion of 5-oxoproline (4.2 to 8.1 mol/mol creatinine) and enzyme assays of leucocyte extracts revealed a profound deficiency of 5-oxoprolinase. However, normal urinary organic acid profiles were found in the younger child. In view of their distinct dysmorphic features and severe growth deficiency, these siblings cannot be considered as Rett Syndrome variants. The Dubowitz and carbohydrate-deficient glycoprotein syndromes were also excluded clinically and biochemically respectively. We conclude that these patients suffer from a hitherto undescribed autosomal recessive disorder, unrelated to the 5-oxoprolinase deficiency of the elder sib. CONCLUSION: The present findings give evidence that 5-oxoprolinase deficiency is not associated with a distinct morbid phenotype.

Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial.

Hydroxyurea (HU) enhances the synthesis of fetal hemoglobin (HbF) and can improve the clinical course of some adult patients with sickle cell anemia (SCA). In a randomized trial, we studied the biologic effects and the clinical benefit of HU in children and young adults with severe SCA. Twenty-five patients (median age, 9 years) were randomized to receive either HU (at the initial dosage of 20 mg/kg/d) or a placebo for 6 months and were then switched to the other arm for the next 6 months. Among the 22 evaluable patients (median age, 8 years), significant increases in HbF and mean corpuscular volume occurred during the HU treatment period. The white blood cell and reticulocytes counts decreased significantly, but these changes were not clinically relevant. Sixteen of 22 patients (73%) experienced a complete disappearance of events requiring hospitalization. The number of days of hospitalization as well as the number of hospitalizations for patients on HU, as compared with those for the patients receiving placebo, were significantly reduced. We conclude that treatment with HU in children and young adults is feasible, well-tolerated, and improves the clinical course of SCA. The long-term effects of HU require further investigation.

Determination of humoral immunoglobulins M and G directed against mycobacterial antigen 60 failed to diagnose primary tuberculosis and mycobacterial adenitis in children.

The serodiagnosis of primary tuberculosis (TB) and mycobacterial adenitis in children was tried using the Anda-Tb tests (Anda Biologicals, France) that measure immunoglobulins (Ig) M and G directed against mycobacterial antigen 60 (A60) by enzyme-linked immunosorbent assay. The 188 cases studied included 81 healthy or mycobacteria-unrelated diseased children with no reaction to tuberculin skin test (STN); 9 recent BCG vaccination (BCG); 35 asymptomatic (AsTB), 29 symptomatic (STB) primary TB and 11 adenitis caused by atypical mycobacteria from the group avium-intracellulare-scrofulaceum (MAIS) tested before treatment; and 23 past primary TB tested at different times after completion of specific treatment (past TB). The individual IgM and IgG levels largely overlapped whatever the clinical status of the children. Setting the normal upper limit at the 95th percentile of the STN values, which by definition gives 95% specificity, the highest IgM sensitivity was found in past TB (35%), AsTB showing 23%, STB 17%, and MAIS 18% sensitivity. IgG sensitivity was also the highest in past TB (26%) and was equal to 6, 14, and 9% in AsTB, STB, and MAIS, respectively. Positive and negative predictive values and the test efficiency (63 and 62% for IgM and IgG, respectively) were far too low. Combining positivity for IgM and/or IgG did not improve the results. In our study, the anti-A60 IgM and IgG measurements using the Anda-Tb tests in primary TB and mycobacterial adenitis in children did not prove of any diagnostic help.

[Ambulatory pediatrics in the hospital and at home]. / Pédiatrie ambulatoire à l'hôpital et à domicile.

In paediatrics, ambulatory care under hospital control is ensured both by the out-patient department and by the emergency unit. If socio-economic level and parental availability are taken into account, the hospital remains the most accessible health-care structure in large towns. The common illnesses, in most cases infectious and respiratory, should not encumber the emergency unit, but should instead be taken in charge by a structure where an extended-timetable dispensary and an out-patient clinic by appointment work in parallel. In the most favourable cases, a home care unit completes this out-patient structure. Its main characteristics are as follows: it is exclusively paediatric, and it aims at shortening or avoiding hospitalization. It improves the quality of treatment, provides the family with medico-social support and follow-up that is particularly useful in less favoured settings, and can also offer preliminary training in heavy or chronic cases. Notwithstanding its obvious advantages, budgetary cuts have led to the suppression of home care at Hôpital Saint-Pierre in 1983.

Bone marrow transplantation corrects the splenic reticuloendothelial dysfunction in sickle cell anemia.

In sickle cell anemia (SCA), the loss of reticuloendothelial function is the result of vasoocclusive events occurring in the spleen. Such asplenia occurs early in the course of the disease and is considered to be permanent in late childhood. In this report, three patients 10, 11, and 14 years of age suffering from severe SCA and found to be asplenic were treated by bone marrow transplantation (BMT). Before transplantation, all three patients had loss of reticuloendothelial splenic function, as assessed by the presence of abundant Howell-Jolly bodies on blood smears and absence of technetium 99m (99mTc) splenic uptake. After BMT, Howell-Jolly bodies disappeared from blood smear, whereas 99mTc isotopic scan found normal isotope uptake. Our data indicate that BMT can correct "permanent asplenia" in SCA patients. However, it remains to be determined if such treatment can also correct other SCA-related organ dysfunctions.

Interleukin-2 and soluble interleukin-2 receptor levels in children with active pulmonary tuberculosis and atypical mycobacterial adenitis.

Interleukin-2 (IL-2) level was measured in sera and in supernatants of Purified Protein Derivatives of Tuberculin (PPD) stimulated peripheral blood mononuclear cells (PBMC) cultures from children with active primary pulmonary tuberculosis (TB), or adenitis caused by mycobacteria of the group Mycobacterium avium, intracellulare, scrofulaceum (MAIS). The control groups included BCG vaccinated children (BCG) and children with negative skin test to PPD (NST). High mean IL-2 level was exclusively found in sera of mild TB patients (MTB), and not in sera of MAIS infected or BCG vaccinated children. The IL-2 level increased even more in MTB during treatment. In severe TB (STB) the IL-2 level was not elevated before treatment, but increased also during treatment. IL-2 production in supernatants of PPD stimulated PBMC cultures was increased in MTB as well as in MAIS and BCG subjects. Further, soluble IL-2 receptor (sIL-2R) levels were measured in the different groups of children. With the exception of the STB group, there was otherwise no significant increase of the receptor in the sera levels between groups. During treatment the sIL-2R levels decreased in MTB as well as in STB. A slight but non significant augmentation was found in the supernatants of PBMC cultures stimulated with PPD. This work suggests, along with other referable studies, that IL-2 and sIL-2R levels are inversely modulated by the disease. Indeed, the IL-2 seems to increase in MTB comparatively to NST children, and in treated TB comparatively to non treated TB children. On the other hand, the sIL-2R level was found to decrease in TB under treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fetal alcohol syndrome]. / Le syndrome d'alcoolisme foetal.

Ethanol teratogenicity manifests itself in the form of the foetal alcohol syndrome (FAS). This syndrome is characterised by growth delay, impairment of the central nervous system, and various facial dysmorphisms. We report the case of a 19 month-old boy affected by FAS. In addition to the three common features of FAS, this patient disclosed organic (digestive and cardiac) malformations and cellular chemotaxis deficiency. We have reviewed the literature to provide an update on the clinical signs of FAS. The abnormalities provoked by foetal exposure to ethanol can be very varied, none of them being specific.

[Indications for bone marrow graft in severe hemoglobinopathies]. / Indications des greffes de moelle dans les hémoglobinopathies graves.

Allogenic bone marrow transplantation (ABMT) is the only curative approach for sickle cell anemia and major beta-thalassemia. In sickle cell anemia, ABMT can be proposed for severe clinical disease. In major beta-thalassemia, it must be proposed to young patients who have an HLA identical familial donor.

Performance of an immunoradiometric assay of erythropoietin and results for specimens from anemic and polycythemic patients.

We evaluated a new commercially available two-site immunoradiometric assay (IRMA; BioMérieux 125I-EPO CoatRIA) for erythropoietin (EPO) in human serum. The precision (CV) was 4.1% intra-assay and 8% interassay for a serum pool with an EPO concentration of 17 int. units/L; the detection limit was 0.5 int. unit/L, one order of magnitude lower than by classical radioimmunoassay (RIA), although standardization of IRMA and RIA were similar. Results by both IRMA and RIA are compared for normal subjects, patients with nonrenal noninflammatory anemias, patients with beta-thalassemia major, hemodialysis patients, and patients with primary or secondary polycythemia. Values by IRMA compared well with those by RIA in the upper area of the range; IRMA and RIA values for EPO show parallel expected variations with the degree of anemia. However, because of its greater sensitivity and specificity, we consider the IRMA more appropriate than RIA for investigating patients with sub-normal EPO concentrations.

Vasopressin and gonadotropin deficiency in a boy with the ectrodactyly-ectodermal dysplasia-clefting syndrome.

A boy presented with ectrodactyly (lobster claw deformity), bilateral cleft lip and palate, semilobar holoprosencephaly and microcephaly, associated with congenital hypogonadotropic hypogonadism and central diabetes insipidus. Other aspects of pituitary function were normal. We suggest that the ectrodactyly-ectodermal dysplasia-clefting syndrome can be associated with a variety of hypothalamo-pituitary dysfunctions, in addition to the already described isolated growth hormone deficiency.

Bone marrow transplantation for severe sickle cell anaemia.

Five children with sickle cell anaemia underwent bone marrow transplantation (BMT) for severe clinical disease. The conditioning regimen for BMT was in busulfan plus cyclophosphamide. The allograft contained more than 5 x 10(8) nucleated cells per kg recipient. Prophylaxis of GVHD consisted of methotrexate and cyclosporin A. Therapy was well tolerated. Duration of neutropenia (less than 0.5 x 10(9)/l) was short (14-25 d). Platelet recovery (greater than 50 x 10(9)/l) occurred between day 12 and 45. The patients have been followed up for 8-28 months. No major infections occurred and long-term BMT-related toxicity was limited to mild, chronic GVHD in one patient. Mean haemoglobin levels remained above 10 g/dl. Haemoglobin electrophoresis showed AS patterns in all grafted patients--all marrow donors having sickle cell trait. From our preliminary data, we conclude that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.

Tuberculosis in children: a 13-year follow up of 1714 patients in a Belgian home care centre.

From May 1970 to September 1983, 1714 children with different forms of primary tuberculosis were referred to the paediatric home care centre (Enfants soignés au Foyer, E.S.F.) of the Brussels University Hospital St.-Pierre. They were subdivided in five groups: asymptomatic (33%), symptomatic (28%), dubious tuberculous infections (35%), high-risk contacts (3%) and unestablished diagnosis (1%). They were aged from 10 days to 19 years, and 82% of them were migrants of low socio-economic level. Fifty percent of the symptomatic infections, mainly pulmonary, appeared in children under 3 years of age. An adult source of contamination was identified in 33% of the cases (48% of the symptomatic children). Diagnosis was based on tuberculin screening with a 2IU intradermal test. Gastric aspirates yielded Mycobacterium tuberculosis in 15% of our patients, 11% of them showing resistance to one or more tuberculostatic drugs. Treatment was given to 1359 patients with excellent results. Therapy was shortened during the last 2 years of the study from 12 to 6 months for the asymptomatic patients and from 12 to 9 months for the symptomatic infections. Few complications were observed. Tuberculosis remains a serious cause of morbidity particularly in migrant children. Correct diagnosis and treatment of the disease is very important.

Serum immunoreactive erythropoietin level: a new parameter for monitoring transfusion management of thalassaemia.

Serum immunoreactive erythropoietin (EPO) was measured sequentially in 8 patients with thalassaemia major. The EPO levels were distinctly increased before transfusion; they did not significantly change just after transfusion, but subsequently decreased. Pretransfusion EPO levels were similar to those observed in patients with non renal non inflammatory anaemias of the same severity. Our results show that production of EPO is appropriately increased in thalassaemia major and confirm that stimulation of endogenous erythropoiesis is not completely suppressed by the hypertransfusion regimen commonly used in this disease. As hyperstimulated ineffective erythropoiesis may lead to invalidating complications, we suggest that serum EPO measurements, which are now easily and reliably performed, should be used in monitoring the therapy of thalassaemia major.

Corticosteroids in primary tuberculosis with bronchial obstruction.

The usefulness of prednisolone in combination with the modern potent antituberculous drugs has been studied in 29 children with primary lung tuberculosis and hilar adenopathy causing bronchial obstruction. These children were divided at random in two groups of 15 and 14 patients. Both groups were treated similarly except that one group received prednisolone. Both groups were very similar before the onset of treatment for most variables. Tuberculous infection healed in both groups but the group on steroids improved earlier and had significantly fewer complications, both on radiography and bronchoscopy. Only two of the patients on steroids still had progressive lesions: a very young baby probably because he developed two severe viral infections consecutively, and another infant of 7 months whose treatment was unreliable, as the parents were not very compliant. Some patients initially not treated with prednisolone improved only after it was given. Prednisolone treatment is not recommended when the reliability of the treatment cannot be guaranteed, as the hazard of harm would exceed the expected benefit.