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Biomedical subjects

C Vermylen

Publications and source records attributed to C Vermylen.

At least 55 records · Page 3Linked to original sources

High expression of bcl-2 is the rule in acute lymphoblastic leukemia, except in Burkitt subtype at presentation, and is not correlated with the prognosis.

Bcl-2 expression and its prognostic value were evaluated using the APAAP technique in 40 ALL patients. Because of a possible synergy between c-myc and bcl-2 proteins in cell lines, we compared 40 ALL of either T or B lineage with seven Burkitt's ALL or sporadic Burkitt's lymphomas (BL). We found the same high expression of bcl-2 in adult (Ad) and childhood (Ch) malignancies examined at presentation, regardless of the T or B phenotype. No bcl-2 expression was detectable in BL cases, except for two investigated at relapse. Bcl-2 staining intensity was also not related to the stage of blast differentiation, except in Ad T-ALL, or to the relapse rate. Ki-67, a marker of proliferation, was used to investigate the possible correlation between bcl-2 expression and the proliferative activity. An inverse correlation was found only in BL at presentation. We confirm that bcl-2 expression is the rule in ALL, regardless of the immunophenotypic characteristics at presentation, and that high expression is not correlated with a bad prognosis. Sporadic BL may represent a particular type of tumor, with bcl-2 expression in relapse, but not at presentation.

Adolescent↗

Haematological disturbances during long-term valproate therapy.

A 14-year-old boy with mental retardation presented with severe thrombocytopenia, macrocytic anaemia and allergic dermatitis. He had been treated with valproate for seizures since the age of 2 years. Clinical examination showed severe purpura, mucous bleeding and extensive dermatitis. Tests to detect serum direct antiplatelet antibodies were positive and bone marrow examination revealed myelodysplastic abnormalities. Valproate was discontinued and both dermatitis and general condition of the child improved with normalization of the full blood count. This report suggests that valproate may produce both peripheral immune thrombocytopenia and severe bone marrow depression several years after the initiation of the therapy.

Adolescent↗

Two cases of congenital dyserythropoietic anaemia type I associated with unusual skeletal abnormalities of the limbs.

This report describes the cases of two young female patients with congenital dyserythropoietic anaemia (CDA) type I who presented similar hand and foot skeletal abnormalities: lack of distal phalanges and nails, and syndactyly. Up to now, some morphological malformations have been described in association with CDA type I but there is no report of skeletal defects. These two cases are suggestive of a possible association between this hereditary anaemia and specific skeletal abnormalities of the distal extremities.

Abnormalities, Multiple↗

Evaluation of third-generation screening and confirmatory assays for HCV antibodies.

A third-generation (gen.) screening and immunoblot assay (Ortho EIA-3.0; Chiron RIBA-3 prototype), using antigens derived from the capsid and different nonstructural regions (NS3, NS4 and NS5) of the hepatitis C virus viral genome, were evaluated in comparison with the corresponding second-gen. assays (Ortho EIA-2.0; revised Ortho EIA-2.5; Chiron RIBA-2). In 203 depository sera of blood donors, positive in EIA-2.0, specificity of the screening assays was improved as shown by an increase in positive predictive value for viral carrier state from 0.23 (EIA-2.0) to 0.37 (EIA-2.5) and 0.52 (EIA-3.0). Comparing the confirmation patterns on RIBA-2 and RIBA-3, this amelioration was mainly due to the specific elimination of false-positive c22-3 and c100-3 reactions. Antibody response to the newly added NS5 antigen was not as prevalent as to the other antigens and had only a minor influence in sample allocation. In contrast, screening of 1,560 volunteer blood donors and 47 hemodialysis patients revealed 3 additional positive sera, only reacting with the NS5 antigen. However none of these isolated NS5 reactions could be confirmed on synthetic peptides [INNO-LIA: NS5(p)] and none was PCR positive. A documented seroconversion, detected earlier with EIA-3.0, was related to a better immunological response to the NS3 antigen and not to the additional NS5. From this pilot study third-gen. assays appeared extremely useful in the reevaluation of HCV-seropositive depository sera. However the additional value of the NS5 antigen in blood donor screening is still hypothetical and remains to be established in larger screening studies.

Antigens, Viral↗

Bone marrow transplantation for sickle cell disease. The European experience.

PURPOSE: In Belgium and France, 42 patients underwent bone marrow transplantation (BMT) for treatment of sickle cell disease. PATIENTS AND METHODS: The patients were young and symptomatic, but without chronic organ damage. Engraftment occurred in all patients and was sustained in 36. These 36 patients became free of symptoms and had a change in electrophoresis of their hemoglobin toward the donor's pattern. RESULTS: In five patients, engraftment was followed by bone marrow rejection. Two of these five patients underwent a second transplant, one at 62 days and the other at 21 months after the first transplant, and they are both doing well. The other three patients had autologous recovery of their own bone marrow. One patient died 3 months after marrow transplant of complications of graft-versus-host disease (GVHD). All the other patients are alive, with follow-up ranging from 1 to 75 months. CONCLUSIONS: Concerning the long-term side effects, six patients had chronic GVHD disease. So far, eight patients returned to Africa where they are continuing to do well.

Adolescent↗

Long-term follow-up of residual disease in acute lymphoblastic leukemia patients in complete remission using clonogeneic IgH probes and the polymerase chain reaction.

We sequentially studied bone marrow (BM) samples of 25 patients in complete remission of an acute lymphoblastic leukemia (ALL) using a simplified polymerase chain reaction (PCR) strategy (direct use of the PCR product as a clonogenic probe recognizing rearranged Ig heavy chain sequences) as a first approach. BM aspirates were serially investigated after obtention of a complete response. When sensitivity was less than 1:10(4), the PCR fragment was sequenced and a specific oligonucleotide was synthetized and used as a probe (five cases). Cases in which minimal residual disease (MRD) became undetectable were cross-controlled using either TCR delta rearrangement or a specific translocation to circumvent the problem of false-negative results arising from clonal evolution. The median follow-up was 30 months (3 to 51 months). Within the first 3 months of complete remission, MRD was detectable in 22 of 23 investigated patients and remained so in 19 of 21 patients examined at 6 months, regardless of the long-term clinical outcome. In patients remaining in complete remission at 30 months or more, two patterns of MRD emerged during the follow-up. Either it continuously decreased to ultimately become undetectable (five patients) or remained detectable (five patients) with an increase after discontinuation of treatment in two. In the eight patients who relapsed, MRD persisted throughout the clinical course, and eventually increased 3 to 12 months before relapse was clinically detectable. In one case, clonal evolution of the VDJ heavy chain region was observed and recurrence of MRD shown by the use of TCR delta rearrangement as a control. We conclude that the use of this simplified methodology is a valuable tool for the follow-up of MRD in a majority of ALL patients, though in a few cases, sequencing needs to be performed to achieve a relevant sensitivity. The possibility of clonal evolution requires a cross-control of any sample becoming negative whatever the initial rearrangement used to generate a probe. In patients on therapy, sequential search for MRD seems to be a good tool for predicting the long-term outcome. In addition, patients remaining positive at the time treatment is discontinued or with a high tumor burden after a few months therapy may be at a higher risk of subsequent relapse, although a longer follow-up is needed to answer this question.

Adolescent↗

Bone marrow transplantation in sickle cell anaemia.

Sickle cell anaemia is a hereditary disorder commonly seen in the black population, due to a point mutation in the beta globin gene. The sickle mutation is responsible for an increased rigidity and adherence of the red blood cell leading to haemolytic anaemia and vaso-occlusive episodes. Symptoms include dactylitis, painful crisis, splenic sequestration and the development of multi-organ damage and failure. The progressive loss of splenic function increases the risk of infections. The morbidity and mortality can be reduced by the maintenance of an adequate nutrition, the prevention of infection and the treatment of complications. In some patients severely affected, a chronic transfusion program has to be instigated to maintain a level of haemoglobin S below 50%. New therapeutic strategies include the use of hydroxyurea and maybe, in the future, butyrates to increase the level of foetal haemoglobin. Further studies are needed to evaluate the benefits of such therapies. Bone marrow transplantation represents an attractive therapeutic tool and its role in other haemoglobinopathies like thalassaemia is now well demonstrated. As far as sickle anaemia is concerned, the first report concerned a child with acute myeloblastic leukaemia. The patient is now cured of both the sickle cell anaemia and the leukemia. Since April 1986, 21 patients underwent an allogeneic bone marrow transplantation for sickle cell anaemia in our department. 20 patients became asymptomatic and have an electrophoretic pattern of the haemoglobin similar to that of the donor. One patient died of bone marrow transplantation related complications.

Adolescent↗

Plasma infusion as treatment for 33 children with haemolytic uraemic syndrome: a good therapy?

Between May 87 and December 91, 33 children aged from 2 months to 13 9/12 years were admitted for haemolytic uraemic syndrome (HUS). Treatment consisted of daily fresh-frozen plasma infusion (20 ml/kg/day) during 14 days. On admission, 20 patients (61%) had an oligoanuria: 18 underwent a peritoneal dialysis and 2 an haemodialysis with a median duration of dialysis of 14 days. A good outcome was rapidly observed in all patients. A normalisation of the platelet count and a sustained normal level of haemoglobin were obtained after a median of 8 days. The follow-up ranged from 7 months to 4 8/12 years: all patients had a normal blood pressure with correct growth. Only 3 children (9%) still had urinary abnormalities: one an isolated microscopic haematuria 3 years after diagnosis and 2 others a mild proteinuria after 1 3/12 year and 4 8/12 years with reduction of the renal function to 80% of the normal for the last one. In our series, plasma infusions lead to a rapidly favourable outcome in all patients and seem to be an effective therapy of HUS in childhood.

Child↗

Hepatitis C virus confirmation in blood donor screening.

A combination of different enzyme immunoassays (EIAs) was used for the serological confirmation of sera that were positive in a hepatitis C virus (HCV) second-generation screening EIA. Different reaction patterns were related with the probability of the HCV-carrier state as determined by polymerase chain reaction (PCR). Five hundred and eight sera of volunteer blood donors were send for confirmation and at first reexamined with both Abbott and Ortho second-generation screening EIA. A group of 195 sera, positive in both assays, was further evaluated by the Abbott Supplemental Assay, the Monolisa anti-HCV and an EIA with only the amino terminal part of the nucleocapsid protein as antigen. In addition PCR on the 5'-noncoding region of the viral genome was performed. We observed that 75 of the 78 PCR-positive sera were found in a group of 89 sera that were strongly positive in the four EIAs used. Moreover all but 1 PCR-positive sera were reactive against the nucleocapsid protein of the virus. Hence we concluded that a genuine antibody response to the nucleocapsid protein is highly suggestive for the HCV-carrier state.

Blood Donors↗

Severe idiopathic congenital aplastic anemia: role of hematopoietic growth factors.

A baby boy with constitutional aplastic anemia refractory to treatment with hematopoietic growth factors underwent BMT from an unrelated HLA-compatible donor. The BM failed to engraft but the combination of a conditioning regimen, immunosuppression and hematopoietic growth factors resulted in a recovery of the patient's own BM and a good outcome.

Abnormalities, Multiple↗

Bone marrow transplantation in sickle cell disease: the Belgian experience.

Twenty eight patients underwent bone marrow transplantation (BMT) for sickle cell anemia in Belgium. The patients were originating from Central Africa, were young and symptomatic. Engraftment occurred in all patients and was sustained in 25. In 3 patients, a bone marrow rejection was observed. One of these patients underwent a second BMT and had an uneventful recovery. One patient died 3 months after BMT of graft-versus-host disease (GVHD). Twenty seven patients are alive and 25 are free of vaso-occlusive related manifestations with a follow-up ranging from 4 to 78 months. So far, eight patients went back to Africa and continue to do well.

Adolescent↗

Association of hepatitis C virus carrier state with the occurrence of hepatitis C virus core antibodies.

An enzyme immunoassay (EIA) was developed for the determination of antibodies against the "putative" core protein of hepatitis C virus (HCV). Antigens used were recombinant fragments (amino acids 6-77 or 6-143) of the HCV core protein, produced in Escherichia coli with truncated hepatitis B core (HBc) as fusion protein. Evaluation of 385 sera positive for HCV antibodies by first generation EIA, revealed 98 (25.4%) with HCV core antibodies. HCV-RNA, determined by the polymerase chain reaction (PCR), was exclusively found in the sera positive for HCV core antibodies (89 PCR positives). In random screening of 3,708 sera, 3 sera with HCV core antibodies were found PCR positive. Only 2 of these sera were positive in the first generation EIA. It is concluded that HCV core antibody determination is a reliable test for identifying HCV carriers among blood donors.

Carrier State↗

Visceral and cutaneous leishmaniasis in an European paediatric population.

Six children with leishmaniasis, aged 10 months to 10 years, were treated in the Paediatric Department. Four patients had visceral leishmaniasis (kala-azar): diagnosis was based on bone marrow examination and therapy consisted of a combination of Glucantime and Lomidine. The remaining two children had cutaneous leishmaniasis: diagnosis was made by skin biopsy and the patients were treated with Glucantime alone. In all children, serology was clearly positive at the time of the diagnosis and all patients improved. The only side effects were cough associated with fever in one child, and supraventricular premature beats in another one. They were ascribed to Glucantime, and proved reversible after discontinuation of the treatment.

Animals↗

Confirmation of hepatitis C virus positive blood donors by immunoblotting and polymerase chain reaction.

In a series of 385 sera obtained from volunteer blood donors positive for the first-generation hepatitis C virus assay (Ortho), the viral genome was detected by polymerase chain reaction (PCR) in 89 sera (23%). Most PCR-positive sera were found positive with the c100-3 neutralisation assay (Abbott) and by two second-generation enzyme immunoassays (Abbott, Ortho). However overall specificity of these assays was rather low. By immunoblotting (Innogenetics and Chiron/Ortho) the specificity could be considerably improved and the best correlation with carrier state was obtained when analysing the results for lane-specific reaction: all 89 viral carriers and only 9 other donors had antibodies against structural 'core' epitopes. From the present data we can conclude that in screening a volunteer blood donor population the confirmation of antibodies against 'core' epitopes by immunoblotting is strongly associated with viral carriage.

Base Sequence↗

Bone marrow transplantation in sickle cell anaemia.

Sickle cell anaemia is still responsible for severe crippling and death in young patients living in developing countries. Apart from prophylaxis and treatment of infections, no active treatment can be safely proposed in such areas of the world. Therefore a bone marrow transplantation was performed in 12 patients staying in Belgium and planning to return to Africa. Twelve patients, aged between 11 months and 23 years (median 4 years), underwent a HLA identical bone marrow transplantation. The conditioning regimen included oral busulphan for four consecutive days (4 mg/kg) followed by four days of intravenous cyclophosphamide (50 mg/kg). In 10 patients the engraftment was rapid and sustained. A further patient suffered transient red cell hypoplasia and another underwent a second bone marrow transplantation from the same donor at day 62 because of graft rejection. All patients are alive and well with a follow up ranging from 9-51 months (median 27 months). In all cases a complete cessation of vaso-occlusive episodes and haemolysis was observed as was a change in the haemoglobin pattern in accordance with the donor's electrophoretic pattern.

Adolescent↗