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Biomedical subjects

E Vilmer

Publications and source records attributed to E Vilmer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Infusion of Fc gamma fragments for treatment of children with acute immune thrombocytopenic purpura.

Treatment of acute immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIG) induces partial or complete responses, shown by transient or persistent increases in platelet count. The clinical benefit could be due to blockade of the Fc gamma receptor (Fc gamma R); platelets sensitised by IgG could not be cleared by cells of the reticuloendothelial system if Fc gamma R on these cells was blocked with IVIG. To find out whether this putative mechanism is correct, we treated twelve children who had acute ITP with intravenous infusions of Fc gamma fragments. Eleven children showed rapid increases in platelet counts to above the critical value of 50 x 10(9)/L, thereby avoiding major haemorrhagic risk. The response was stable in six patients and transient in five. No adverse reactions were observed. In responders who had detectable platelet-associated IgG before treatment (> 1500 IgG per platelet), platelet IgG fell substantially with treatment. Serum soluble CD16 (sCD16 or sFc gamma RIII) concentrations, measured in five children, showed transient or stable increases that correlated with the rise in platelet count. No sCD16 was detected in the Fc gamma preparation used. We conclude that the infusion of Fc gamma fragments is an efficient treatment of acute ITP in children. The efficacy of Fc gamma fragments strengthens the hypothesis that Fc gamma R blockade is the main mechanism of action of IVIG in ITP, although other immunoregulatory mechanisms triggered by the presence of increased sCD16 concentrations in serum could be involved in the clinical benefit observed.

Adolescent↗
PubMed1993

Busulfan disposition below the age of three: alteration in children with lysosomal storage disease.

Busulfan disposition is age-dependent with a higher clearance and a larger volume of distribution in children than in adults. The optimal dosage of busulfan needed to achieve bone marrow (BM) displacement in young children with malignant or nonmalignant disease remains to be defined. Using a gas chromatography-mass spectrometry assay, we evaluated plasma pharmacokinetics of busulfan in 33 children (median age, 9 months; range, 2 months to 2.75 years) with immune deficiencies, lysosomal storage diseases, acute leukemias, and malignant lymphohistiocytosis after an oral dose ranging from 0.9 to 2.6 mg/kg. The busulfan clearance (assuming a bioavailability of 1) ranged from 2.1 to 13.4 mL/min/kg with a mean of 6.8 mL/min/kg, which is higher than that reported in older children (4.5 mL/min/kg) and adults (2.9 mL/min/kg). Six children with lysosomal storage disease (5 with Hurler's disease, 1 with San Filippo's disease) had a prolonged elimination half-life (4.9 v 2.4 hours), a larger volume of distribution (3.4 v 1.2 L/kg) and a faster clearance (8.7 v 6.3 mL/min/kg) than the other 27 children. This suggests that a higher dose of busulfan will be required to achieve BM displacement in children with lysosomal storage disease. Over the dose range of 0.9 to 2.6 mg/kg, busulfan pharmacokinetics were linear. However, only 46% of the interpatient variation in systemic exposure could be ascribed to the dose. Given the wide interpatient variability in busulfan disposition, dose adjustment and drug monitoring will be needed to achieve the optimal dosage of busulfan in young children. The plasma busulfan levels required to achieve BM displacement need to be defined, especially in lysosomal storage diseases.

Age Factors↗
PubMed1993

[Microangiopathic anemia following thrombopenic purpura].

BACKGROUND: Chronic relapsing microangiopathic hemolytic anemia is rare in children. This report describes a case associated with thrombocytopenia following idiopathic thrombocytopenic purpura. CASE REPORT: A 4 year-old girl was admitted for acute idiopathic thrombocytopenic purpura (platelet count: 12,000/mm3) without anemia or fragmented red cells. The patient was given intravenous gammaglobulins without success, followed by prednisone (2 mg/kg/day). The platelet count was normalized, but decreased when the treatment was discontinued. The patient developed acute intracranial hypertension at the age of 5 yr 8 mo, following two cerebral hematomas. The platelet count was 9,000/mm3. A second course of intravenous gammaglobulins and prednisone was unsuccessful, so a splenectomy was performed. One year later, the patient was admitted because of diffuse purpura, anemia and jaundice. Hematologic findings were: Hb 8.4 g/dl, reticulocytes 448,200/mm3, fragmented red cells 16%, platelets 15,000/mm3, WBC 22,400/mm3. Seroimmunologic investigation showed a high titer of antinuclear antibodies. Examination for viral etiology was negative. Intravenous gammaglobulins had a transient effect on platelets, reticulocytes and fragmented red cells. The patient was then given vincristine plus prednisone; they were only effective when high doses were used. A second intracerebral hemorrhage occurred when the patient was given low doses of drugs. After 3 other hematologic relapses, the vincristine was stopped without further complication. CONCLUSION: The criteria for systemic lupus erythematous were not satisfied, despite the presence of antinuclear antibodies. A congenital deficiency of an unidentified plasma factor that reverses microangiopathic hemolysis and thrombocytopenia was not demonstrated in this patient, who could not be given fresh frozen plasma.

Acute Disease↗
PubMed1992

Cytotoxic T lymphocyte responses in the peripheral blood of children born to human immunodeficiency virus-1-infected mothers.

Cytotoxic T lymphocytes (CTL) are present at high activities in adult patients infected with the human immunodeficiency virus (HIV). In this report, CTL effectors were identified in peripheral blood mononuclear cells (PBMC) of children born to HIV-1-infected mothers. These CTL killed HLA-matched HIV-1-infected H9 target cells or doubly transfected P815-A2-env, gag or nef mouse tumor cells, which expressed the viral antigens in association with HLA-A1/A3 or HLA-A2, respectively. HIV-1-specific CTL were detected early after birth (less than 2 months) and remained present during the asymptomatic phase of the infection. As in HIV-1-infected adults, HIV-specific CTL declined with disease progression. Surprisingly, HIV-1-specific CTL were detected in the PBMC of three children who subsequently became seronegative.

Base Sequence↗
PubMed1992

Restricted diversity of V gamma 9-JP rearrangements in unstimulated human gamma/delta T lymphocytes.

The diversity of human peripheral blood gamma/delta T cells is known to be limited by the preferential use of V genes coding for V gamma 9 (usually linked to JP) and V delta 2. We show that the diversity of these cells is further limited at the junctional region. First, an identical rearrangement is found in 10%-30% of all gamma/delta T cells which contain V gamma 9-JP rearrangements. Second, the vast majority of V gamma 9-JP rearrangements which are different from this predominant sequence have, nevertheless, the same length or code for variable regions whose length differs by only one amino acid (+/- 1). Overall, 30%-50% of V gamma 9-JP rearrangements have a junctional region which encodes for a peptide with the amino acid sequence E VX EL, in which EV is predominantly, but not exclusively, encoded by the germ-line V gamma 9 sequence and EL is encoded by JP. The X amino acid is variable, but a glutamine is over-represented. The diversity of the V gamma 9-JP repertoire is fairly constant in different individuals and at different ages, including before, during and after the post-natal expansion of peripheral blood gamma/delta T cells.

Adult↗
PubMed1992

Ribotyping provides efficient differentiation of nosocomial Serratia marcescens isolates in a pediatric hospital.

Ribotyping with a nonradioactive probing system was used for the epidemiological evaluation of 15 Serratia marcescens nosocomial strains isolated from the stools of 12 children with no apparent illness in five different hospital wards over a 20-day period. Our results indicate that the occurrence of S. marcescens colonization was the result of the spread of a single epidemiological strain in the hematology ward, the oncology ward, and the gastroenterology ward and in two neonates in the neonatology ward, suggesting cross-contamination between the patients in these four wards. This isolate was genotypically unrelated to the bacterial strain found in the three other patients in the neonatology ward. Interestingly, one patient in the neonatology ward harbored these two genotypically different strains. Finally, the patient in the intensive care unit was colonized with a different strain. We find ribotyping to be a more reliable technique than biochemical typing. The results of ribotyping are more easily interpreted than are those of total DNA analysis, with an equivalent degree of discrimination.

Bacterial Typing Techniques↗
PubMed1992

Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1.

Antigens, CD↗
PubMed1992

Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872).

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.

Adolescent↗