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Biomedical subjects

M Toppet

Publications and source records attributed to M Toppet.

At least 19 recordsLinked to original sources
PubMed2001

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)

Acute Disease↗
PubMed2001

[Prevention of hemoglobinopathies in Brussels: a necessity?].

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.

Algorithms↗
PubMed2000

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.

Administration, Inhalation↗
PubMed1999

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.

Adolescent↗
PubMed1998

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.

Anemia, Sickle Cell↗
PubMed1997

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.

Brain Diseases↗
PubMed1996

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.

Adolescent↗
PubMed1994

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.

Antibodies, Bacterial↗
PubMed1993

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.

Adolescent↗
PubMed1992

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.

Anemia, Sickle Cell↗
PubMed1992

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.

Abnormalities, Multiple↗
PubMed1992

[Indications for bone marrow graft in severe hemoglobinopathies].

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.

Anemia, Sickle Cell↗
PubMed1992

[Fetal alcohol syndrome].

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.

Abnormalities, Multiple↗
PubMed1992

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.

Adolescent↗
PubMed1991

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.

Adolescent↗
PubMed1991

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.

Adolescent↗
PubMed1990

Desferrioxamine improves neutrophil phagocytosis in thalassemia major.

The aims of the present study are: first, to assess the toxic role of serum from thalassemic patients in phagocytosis of PMN from healthy controls, and second, to seek to determine whether serum and cellular disturbances of polymorphonuclear neutrophils (PMN) phagocytosis, observed in thalassemic patients, can be prevented and/or corrected by use of desferrioxamine (DFX). Two kinds of in vitro incubations--without or with DFX--were performed. PMN or serum from thalassemic patients or from healthy controls was used. First, a phagocytosis defect of 3 different bacteria species was induced in PMN from healthy controls by incubation in thalassemic serum. Second, DFX could prevent, already at 1 microM, the phagocytic defect induced in normal PMN by the incubation with thalassemic serum, with disappearance of the toxic role of thalassemic serum at higher concentrations. Third, improvement of the phagocytosis defect of PMN from thalassemic patients was also observed at 1 microM of DFX for the 3 bacteria species. Normalization was obtained at higher concentrations for gram-negative bacteria. In vivo studies revealed, after a 3 hr subcutaneous infusion of DFX into 3 thalassemic patients, an improvement of the phagocytosis results and a decrease of the Prussian Blue reactivity of the PMN. It is concluded first that an iron-mediated defect in phagocytosis can be induced in normal neutrophils by incubation in serum from thalassemic patients, and second that a precautious and intensive chelation therapy seems to be advantageous for increasing PMN defense against infectious agents. Special care must nevertheless be taken in order to detect rapidly opportunistic (such as Yersinia) infections.

Adolescent↗