PubMed Health⌕ Search

Biomedical subjects

F Mielot

Publications and source records attributed to F Mielot.

At least 19 recordsLinked to original sources
PubMed2000

Dyserythropoiesis associated with a fas-deficient condition in childhood.

Defective lymphocyte apoptosis caused by mutations of the Fas gene can result in an autoimmune lymphoproliferative syndrome (ALPS) in humans. We report two cases of dyserythropoiesis associated with a Fas-deficient condition in childhood. In both cases, dyserythropoiesis predominated on the more mature erythroblasts, and was associated with a lymphoproliferative syndrome as well as with haemolytic anaemia, hypergammaglobulinaemia and the expansion of an unusual population of CD4- CD8- T cells that express the alpha/beta T-cell receptor. The regression of dyserythropoiesis under steroid therapy suggested that it resulted from an autoimmune mechanism, itself secondary to the lymphocyte Fas apoptosis deficiency. Fas-defective apoptosis may be a new aetiology for childhood dyserythropoiesis.

Anemia, Hemolytic↗
PubMed2000

[Macrophage activation syndrome in primary human herpes virus-6 infection: a rare condition after liver transplantation in infants].

Human herpes virus-6 primary infection generally occurs during the first three years of childhood and is generally asymptomatic. The virus has been identified as the causal agent of exanthemum subitum in children or mononucleosis-like disease in adults, and may also cause several disorders in immunocompromised patients. We report a clinical case of acute rejection observed 29 days after orthotopic liver transplantation in a 22-month-old child associated with acute hepatitis and a hemophagocytic syndrome on day 38. Human herpes virus-6 primary infection was identified based on several virological tests: seroconversion, detection of viral DNA in bone marrow and peripheral blood after polymerase chain reaction, and detection of viral replication in peripheral blood. Tests for Epstein-Barr virus, cytomegalovirus or Parvovirus B19 infections were negative. After treatment by ganciclovir (Cymévan(R)), clinical status improved.

Acute Disease↗
PubMed1999

The GEN.S: a fortuitous finding of a routine screening test for hereditary spherocytosis.

As part of the evaluation of the GEN.S (Coulter), we compared the Mean Corpuscular Volume (MCV) to the Mean Spherized Corpuscular Volume (MSCV) assessed during the reticulocyte count procedure under hypo-osmotic conditions. A sub-group of patients with hereditary spherocytosis (HS) was singled out: in all of them, the MSCV became smaller than the MCV. As the cell volume normally increases in red cells derived from other patients in the same conditions, we decided to further study the reason for this particular behaviour of HS red cells. Whereas normal red cells are able to undergo an osmotic expansion, the spherocytes reach a critical osmotic volume leading to cell fragmentation consistent with the decrease of MSCV. This fortuitous finding is likely to be a reliable improvement for the routine screening of HS.

Adolescent↗
PubMed1999

Suppression of CDA II expression in a homozygote.

The CDAN2 gene, responsible for congenital dyserythropoietic anaemia, type II (CDA II), was recently mapped to 20q11.2. We report data on an additional member of a previously studied CDA II family. This member had always been regarded as haematologically normal. Unexpectedly, she had the same microsatellite assortments around the CDAN2 alleles as her three sisters with CDA II. In particular, she was a homozygote for microsatellites D20S863 and D20S841. This prompted an analysis of all facets of her phenotype. The Ham test was negative. The bone marrow smears contained a normal proportion of binucleate erythroblasts. Electron microscopy revealed the absence of extensive stretches of cisternae beneath and parallel to the inner surface of the erythroblast plasma membrane. Proteins of the endoplasmic reticulum, which contaminate the reticulocyte plasma membrane in CDA II patients, were missing. Only the shape of the band 3 peak appeared slightly altered. This case exemplifies that homozygosity (or compound heterozygosity) for a deleterious gene may be silenced, or almost completely silenced. In recessively inherited diseases, suppressed phenotypes tend to be overlooked in siblings where both patients and unaffected individuals are expected.

Anemia, Dyserythropoietic, Congenital↗
PubMed1998

Myelodysplastic syndromes in childhood: is the FAB classification relevant? Report of 81 children from a French multicentre study. French Group of Cellular Hematology.

We reviewed the peripheral blood and bone marrow smears of 81 children with myelodysplastic syndrome (MDS). The morphological FAB classification was applicable in 59 children (72.8%): RAEB and RAEBt were the most frequent, 32 cases (39.5%). CMML was observed in 15 cases (18.5%) and in 25% of them, serological evidence for a recent EBV infection was demonstrated. In 22 cases (27.2%), the FAB classification was not convenient. In some of these children, dysmyelopoiesis was associated with constitutional disorders. Among these various inherited conditions, Down syndrome in which myelodysplasia is the expression of an abnormal clonal hematopoiesis, and mitochondrial cytopathies in which MDS is the hematological expression of a polyclonal multi-organ disease. The FAB classification does not appear to be satisfactory for all the disorders included in the group of childhood MDS and should be modified for specific use in children.

Adolescent↗
PubMed1995

Abnormal chromatin clumping in granulocytes in a case of Ph1-negative, BCR-ABL rearrangement positive, haematologically atypical chronic myeloid leukaemia (CML).

In the present study, we report the case of a patient displaying an abnormal chromatin clumping (ACC) syndrome, a rare disease which shares features with both myeloproliferative and myelodysplastic disorders. Although various non specific cytogenetic abnormalities have been observed in ACC, the presence of a Ph1 chromosome has not been reported. In our patient, despite a lack of Ph1, PCR analysis of blood and bone marrow samples revealed a BCR-ABL rearrangement. These results indicate that at least some cases of ACC syndrome could represent a form of Ph1-negative chronic myeloid leukaemia.

Aged↗
PubMed1994

Refractory anaemia and mitochondrial cytopathy in childhood.

We report two cases of childhood myelodysplasia (MDS) related to a mitochondrial (mt) cytopathy that illustrate the difficulty in recognizing such disorders in patients with solely haematological signs. Both patients have refractory anaemia with ring sideroblasts and vacuolization of haemopoietic precursors. These cytological features are similar to those observed in Pearson's disease, recently identified as a mitochondrial disease, and are strongly suggestive of a mitochondrial enzyme defect. The diagnosis of mitochondrial cytopathy was established on Southern blotting of mt DNA, showing a mt DNA deletion, or on the impairment of the respiratory chain enzyme activities. The absence of cytogenic abnormalities, and the polyclonal pattern of peripheral neutrophil and lymphocyte fractions, suggest that, in mt cytopathies, MDS cannot be considered as a truly malignant disorder.

Anemia, Sideroblastic↗
PubMed1993

Initial assessment of the beneficial effect of partial splenectomy in hereditary spherocytosis.

Clinical manifestations of hereditary spherocytosis (HS), the most common red blood cell (RBC) membrane disorder, can be abrogated or markedly reduced by splenectomy. However, concerns regarding risks from overwhelming infections after splenectomy have restricted its use, especially in children. This study was designed to determine if partial splenectomy can decrease the hemolytic rate while maintaining phagocytic function of the spleen. Partial splenectomy was performed in 11 children (age 2 to 13) with HS. The effect on hemolytic rate was assessed by comparing the presurgical and postsurgical values for hemoglobin, reticulocyte number, and RBC life span. The residual splenic phagocytic function was assessed using technetium 99m scans and by enumerating the percentage of pitted RBCs in circulation. There were no complications from the surgical procedure in any of the 11 individuals. Following partial splenectomy, hemoglobin increased on the average by 3 g/dL, reticulocyte count decreased by 300 x 10(6)/L, and RBC life span was substantially prolonged. Normal technetium uptake was noted in the splenic remnant and the percentage of pitted RBCs was in the normal range. Partial splenectomy is effective in decreasing the hemolytic rate while maintaining residual splenic phagocytic function of the spleen in HS. We conclude that the use of this procedure as treatment for RBC membrane disorders warrants consideration, especially in infants under 5 years of age who need frequent transfusions.

Adolescent↗
PubMed1992

Macrophage activation syndromes.

The clinical and laboratory features of 47 cases of macrophage activation syndrome (MAS) were reviewed in a workshop within the Groupe Français d'Hématologie cellulaire. There was no predilection for a particular age group, while common symptoms at presentation included fever, hepatic and splenic enlargement and profound depression of blood count. Examination of bone marrow aspirates allowed diagnosis to be established in almost all cases. The most characteristic sign of MAS was the presence of well differentiated macrophages without notable cytologic abnormalities but shown to be actively ingesting haematopoietic elements. Haemophagocytic syndromes generally occur in patients who develop infections in the context of preexisting immunologic abnormalities or neoplasms. In the majority of patients evolution of the disease was regressive, once spontaneously but often after antibiotic, antiparasitic and/or antiviral treatment accompanied or not by corticotherapy and/or chemotherapy. Some regressive phases were followed by more or less long term relapse, especially in the case of associated systemic lupus erythematosus. There exists at present no explanation for the occurrence of MAS, although one may remark its association with other pathologies, in particular congenital or acquired immune deficiencies and haemopathies. Several hypotheses have been proposed to explain the appearance and evolution of the disease and at present two pathways of investigation of MAS seen to merit attention: exploration of macrophages themselves and their secretion products and exploration of lymphocytes and NK cells. The current possibilities for these investigations should lead to a greater understanding of the physiopathology of MAS and it is to be hoped that a better application of appropriate therapy will enable control of its evolution.

Adolescent↗
PubMed1992

[Regressive myelodysplastic syndromes in children. Committee on Childhood Myelodysplasia of the Society of Pediatric Hematology and Immunology].

BACKGROUND: As in adults, myelodysplastic syndromes in children are often preleukemic and their spontaneous remission is exceptional. CASE REPORTS: Case 1. A girl, aged 8 years, developed pancytopenia with macrocytic anemia. The myelogram and bone marrow biopsy showed dyserythropoiesis with macroblastosis, but without sideroblasts. The chromosome configuration was normal and the negative results of other investigations led to the diagnosis of refractory anemia without any known cause. Bone marrow transplantation was considered, but a spontaneous remission intervened and has persisted for 3 years. Case 2. A girl, aged 5 years, was investigated for worsening of a macrocytic anemia that had been present for 3 years, without changes of granulocytes and platelets. The myelogram showed dyserythropoiesis with megaloblastosis and sideroblasts. No known cause could be identified. As for the preceding patient, a spontaneous remission occurred, and has persisted for 3 years. Case 3. A girl, aged 5 months, developed pancytopenia. The myelogram showed dys-megakaryocytopoiesis. All hematologic data spontaneously normalized after 1 year, and have remained so 1 year later. CONCLUSION: The spontaneous remission, that has occurred in our 3 patients, has been reported in one only adult. This possibility precludes considering all the myelodysplastic syndrome in children as preleukemic, and suggests that bone marrow transplantation is not urgent in these situations.

Age Factors↗
PubMed1991

Acute megakaryocytic leukemia (AMKL) with major myelofibrosis in an infant. Diagnosis by liver biopsy and response to treatment.

An infant presented with enlarged liver and spleen and profound pancytopenia. Severe marrow fibrosis impeded the diagnosis which was achieved by liver biopsy: Fibrosis surrounded foci of blasts which were shown by immunologic markers to originate from the megakaryocytic lineage. Complete sustained remission was obtained by low-dose aracytine therapy. The child was disease-free at 40 months' follow up.

Biopsy↗
PubMed1989

Inactivated X chromosome fold in human leukemia and related clonal disorders.

A disturbance of the X chromosome inactivation process has been demonstrated in some human tumors. In order to study this phenomenon in leukemia, the site of unusually frequent folding in Xq13-q21 was used as a morphological marker. A total of 858 GTG-banded mitoses from 61 women with different hematological malignancies were analyzed, 35 of them with normal karyotype and 26 with chromosome aberrations. The folding patterns and the fold percentage remained unchanged in our patients. Using this marker, X-inactivation could easily be verified in leukemia and related disorders on routine preparations.

Adolescent↗
PubMed1988

Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia.

The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period. Thus, in these patients, the characteristic "block" in granulocytic maturation observed in vivo was reproduced in vitro in long-term cultures. Granulocytic differentiation proceeded normally in long-term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long-term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo.

Agranulocytosis↗
PubMed1987

[Acquired deficiencies in antithrombin III and C protein during treatment with L-asparaginase].

Fourteen children treated by L-Asparaginase for acute lymphoblastic leukemia had sequential coagulation studies performed including cephalin-kaolin time, Quick time, fibrinogen, factors II, VII + X and V, as well as antithrombin III and protein C, the major coagulation inhibitors. A severe antithrombin III and protein C deficiency was observed during therapy, with a coexisting hypocoagulability. This equilibrium partially explains the lack of thrombo-embolic phenomena in these children, despite the risk factors present. Although no substitutive therapy was instituted in these cases, their use in high-risk cases is discussed.

Adolescent↗
PubMed1985

[Erythroblastopenia in a child during treatment of a neuroblastoma].

A 4 year-old child being treated for neuroblastoma developed erythroblastopenia. We used specific erythroid lineage markers (hemoglobin and spectrin) and in vitro erythroid colony assays to characterize this hematologic picture and discuss its relationships with the disease and its treatment.

Bone Marrow↗