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S Blanche

Publications and source records attributed to S Blanche.

At least 19 recordsLinked to original sources
PubMed2007

A gene responsible for Ghosal hemato-diaphyseal dysplasia maps to chromosome 7q33-34.

Ghosal hemato-diaphyseal dysplasia is a rare autosomal recessive disorder characterized by a progressive sclerosing diaphyseal dysplasia and refractory anemia. The pathogenesis and genetic bases of this syndrome remain hitherto unknown. We have performed a genome wide search in two inbred families originating from Algeria and Tunisia. Here, we report on the mapping of a disease gene to chromosome 7q33-34 (Zmax = 4.21 at theta = 0 at locus D7S2513) in a 3.4 Mb defined by loci D7S2560 and AC091742. Ongoing studies will hopefully lead to identification of the disease-causing gene.

Adult↗
PubMed2006

Description of an adenovirus A31 outbreak in a paediatric haematology unit.

Adenovirus infections result in significant morbidity and mortality in allogeneic haematopoietic stem cell transplanted (hSCT) children. Adenovirus from species C and B account for more than 90% of adenoviruses recovered after hSCT. However, infections due to adenovirus A31 have been increasingly reported in recent years. Between April 2002 and April 2005, blood samples obtained every 2 weeks from 58 hSCT children were screened for adenovirus species A to C by quantitative real-time PCR. Phylogenetic analysis was realized after amplification and sequencing of the entire hexon gene. Fifteen cases of adenovirus infection with viraemia were recovered during this 3 years period. During spring/summer 2003, seven cases occurred and were due to an adenovirus species A. Phylogenetic analysis of the seven strains showed that they belonged to the A31 genotype and shared 100% homology. Clinical features of the seven HSCT children with A31 adenovirus viraemia are described. We describe here an epidemic spread of adenovirus genotype A31 in a paediatric haematology unit. Timing, location and hexon gene genotyping results highly suggested a nosocomial origin to this epidemic. The burden of adenovirus A31 infection needs to be further assessed in this context.

Adenovirus Infections, Human↗
PubMed2005

Parental consent in paediatric clinical research.

AIMS: To assess parental understanding and memorisation of the information given when seeking for consent to their child's participation to clinical research, and to identify the factors of significant influence on parents' decision making process. METHODS: Sixty eight parents who had been approached for enrolling their child in a clinical oncology or HIV study were asked to complete an interview. Their understanding was measured by a score which included items required to obtain a valid consent according to French legislation. RESULTS: Items that were best understood by parents were the aims of the study (75%), the risks (70%), the potential benefits to their child (83%), the potential benefits to other children (70%), the right to withdraw (73%), and voluntariness (84%). Items that were least understood were the procedures (44%), the possibility of alternative treatments (53%), and the duration of participation (39%). Less than 10% of the parents had understood all these points. Ten parents (15%) did not remember that they had signed up for a research protocol. Thirty three parents (48%) reported no difficulty in making their decision. Twenty four parents (38%) declared that they made their decision together with the investigator; 26 (41%) let the physician decide. Fifty four parents (78%) felt that the level of information given was satisfactory. CONCLUSION: There was an apparent discrepancy between parents' evaluation of the adequacy of the information delivered and evaluation of their understanding and memorisation. The majority of parents preferred that the physician take as much responsibility as possible in the decision making process.

Adolescent↗
PubMed2005

Transient familial haemophagocytic lymphohistiocytosis reactivation post-CD34 haematopoietic stem cell transplantation.

Familial haemophagocytic lymphohistiocytosis (FHLH) is a genetic disorder caused by defective lymphocyte cytotoxicity, resulting in impaired lymphocyte homeostasis and macrophage infiltration of solid tissues and bone marrow, with extensive haemophagocytosis. It is invariably fatal unless treated by allogeneic haematopoietic stem cell transplantation (HSCT). In a retrospective analysis of 11 cases of FHLH, transplanted in one centre between January 1999 and December 2003, it was found that host T cell expansion occurred early after HSCT in a setting of a viral infection (cytomegalovirus and Epstein-Barr virus respectively) in two cases who received T cell-depleted HSCT. Transient recurrence of clinical and biological manifestations of FHLH was observed, despite evidence for donor cell engraftment. Secondary development of donor T cells led to stable mixed chimaerism and sustained remission of FHLH. Detection of host-derived T cells soon after HSCT in a patient with FHLH should thus not mistakenly be taken as a manifestation of graft rejection.

Antigens, CD34↗
PubMed2004

DSM-IV mental disorders and neurological complications in children and adolescents with human immunodeficiency virus type 1 infection (HIV-1).

AIM: - To study the types of psychiatric problem encountered in children infected with the human immunodeficiency virus (HIV) and their relationship to central nervous system disorder and the severity of infection. METHODS: - 17 HIV-infected children presenting with psychiatric problems were included. Mental disorders were evaluated according to DSM-IV criteria. Neurological disorders and progressive encephalopathy (presence or absence) diagnosis were evaluated by clinical and radiological examination. The severity of infection was assessed by the percentage of CD4 lymphocytes. RESULTS: - The most frequent diagnoses were major depression (MDD: 47%) and attention deficit hyperactivity disorder (ADHD: 29%). Major depression diagnosis was significantly associated with neuroimaging or clinical neurological abnormalities (p < 0.01). In contrast, no association was found between hyperactivity diagnosed according to DSM-IV criteria and central nervous system disorder. Percentage of CD4 lymphocytes were close to 0 for more than 80% of children presenting with psychiatric complications. CONCLUSION: - The very low % of CD4 lymphocytes of these children suggest that the appearance of a psychiatric complication should be regarded as a factor indicating severe HIV infection. Depressive disorders may be a clinical form of encephalopathy.

AIDS Dementia Complex↗
PubMed2004

Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors.

SUMMARY: Hematological inherited diseases can be cured by hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling donor (MSD), but the outcome of unrelated donors (URD) or haploidentical donors (HMD) has been a cause of concern. In all, 94 children affected with inherited diseases underwent HSCT at a single center using MSD (group A, n=31), URD (group B, n=23) or HMD (group C, n=40). There was no difference in the rate of engraftment or in the incidence of grades III-IV acute graft-versus-host disease (GVHD) between the groups. Survival rate was 80.6% in group A, 62.5% in group B and 47.5% in group C (P=0.023). In group B, survival rate was 73.7% in the subgroup with zero or one class I mismatch, and 25% in the subgroup with two or more class I mismatches (P=0.04). In group C, survival rate was 83.3% in the 9/10-identical subgroup, 64.3% in the seven or 8/10 subgroup, and 25% in the five or 6/10 subgroup (P=0.0007). Thus, engraftment, incidence of GVHD and survival are similar in recipients of grafts from MSD, URD with 0-1 class I-mismatch, or HMD with at least 7/10 HLA matches. The low success of HSCT using more disparate donors suggests reserving them for patients with very poor prognosis.

Adolescent↗
PubMed2004

Does haploidentical transplantation in children with primary immunodeficiencies have the potential to exploit donor NK cell alloreactivity?

Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primary immunodeficiencies. The conditioning regimen consisted of busulfan and cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis or CD34+ selection. Two patients died in the first month. The remaining 38 patients were divided into those with (n=13) and those without (n=25) donor potential to exert NK cell alloreactivity. Engraftment was similar in the two groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft-versus-host disease (GVHD) tended to be lower in the group with donor potential to exert NK cell alloreactivity, but the difference was not significant. In conclusion, in this series of patients with primary immunodeficiencies, donor potential to exert NK cell alloreactivity was not associated with significant advantages in engraftment and prevention of acute GVHD.

Child, Preschool↗
PubMed2004

PENTA guidelines for the use of antiretroviral therapy, 2004.

There have been few major advances in paediatric HIV management over the last 2 years. Decisions about starting antiretroviral therapy can now be based on a recent large meta-analysis of the predictive value of CD4 and HIV RNA viral load (VL) in nearly 4000 untreated children, which is discussed in these updated guidelines. Risk estimates for progression to AIDS and death using surrogate markers can now be broken down by age, allowing more accurate discussion with families. In addition, there is increasing recognition of the problems of long-term adherence, drug resistance and cumulative toxicity in adults and children. The controversy over whether to treat asymptomatic infants continues. For older children more data on the efficacy of ritonavir boosted protease inhibitor (PI) regimens suggests that these may be the PI option of first choice. There is still no adult or paediatric trial evidence on which to base decisions about whether to start with PI- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based regimens, but the PENPACT 1 trial, which is addressing this question, is ongoing. There are increasing moves to provide simpler antiretroviral therapy (ART) regimens, including once daily dosing, but these lag behind adult regimens because of the paucity of pharmacokinetic data. Resistance assays should now be performed in all HIV-infected infants exposed to ART in pregnancy. Therapeutic drug monitoring may be very important in children because of high between- and within-child variability in drug absorption and metabolism. A trial to evaluate this should start shortly in Europe (PENTA 14 trial). The value of resistance tests for choice of second-line and subsequent choices of ART regimens remain unproven (the PERA trial will report late in 2004), but resistance assays are increasingly being used. The issue of when to switch therapy also remains unanswered and is being addressed within the PENPACT 1 trial. Regular formal assessment of adherence is now the standard of care, and routine monitoring in the clinic for lipodystrophy syndrome (LDS) and other ART toxicities is increasingly important. These guidelines will be updated again in 2006.

Anti-HIV Agents↗
PubMed2003

Hematopoietic stem cell transplantation in patients with severe Langerhans cell histiocytosis and hematological dysfunction: experience of the French Langerhans Cell Study Group.

The aim of this study was to assess the results of hematopoietic stem cell transplantation (HSCT) in refractory Langerhans cell histiocytosis (LCH). Among 85 patients with LCH and hematological dysfunction diagnosed in France between 1987 and 2000, eight received HSCT in six institutions. Median age at diagnosis was 0.54 years. The median LCH activity score at diagnosis was 10 (range 3-20). All patients responded poorly to initial chemotherapy. At the time of HSCT, the median activity score was 16.5 (range 7-18). HSCT was autologous in three cases and allogeneic in five cases. The conditioning regimen consisted of TBI in two cases and chemotherapy alone in six cases. Conditioning had to be attenuated in two patients. All patients had persistent active disease after autologous HSCT, which was fatal in two cases and controlled by chemotherapy in one case. After allogeneic HSCT, two patients died from toxicity and three had complete responses; two patients had had no recurrences after 21 months and 7 years of follow-up, while the other patient relapsed and died from sepsis related to splenectomy. HSCT for refractory LCH can thus be highly toxic but can also achieve sustained disease control.

Chimera↗
PubMed2003

[HIV-1 infection in children in African countries].

The prognosis of HIV infection is dramatic for children living in poor countries. Over 50% die within two years. The World Health Organization has estimated that 1500 children will be infected daily until large-scale national programs for prevention of mother-to-child transmission are implemented. A better understanding of the causes underlying early morbidity could lead to a substantial reduction in mortality pending use of antiretroviral drugs which have demonstrated promising results in preliminary tests on children in poor countries.

Adult↗
PubMed2002

Aspergillus antigen and PCR assays in bone marrow transplanted children.

Screening for Aspergillus antigen and DNA has been introduced for the early diagnosis of invasive aspergillosis (IA) in adults, but data in children at risk are scarce. Seventeen 1-108 month-old children were screened for Aspergillus antigenaemia by a commercial assay before and after bone marrow transplantation (BMT). Seventy-one serum samples were examined retrospectively by a novel nested PCR assay. Results of both assays were correlated with clinical, radiological and microbiological findings used for the definition of invasive aspergillosis by the European Organisation for Research and Treatment of Cancer (EORTC). Three cases of probable or possible IA were defined, and in 14 children invasive aspergillosis was ruled out. In 10 children, Aspergillus antigen was detected in at least two consecutive serum samples, a microbiological EORTC criteria of IA. Specific DNA was detected in 8 antigen-positive and 2 antigen-negative sera. A positive predictive value of 20% was calculated for both assays. Hence, a high rate of positive results of antigen Elisa and PCR assays in BMT children are due to transient antigenaemia and fungaemia without clinical relevance. According to our data, prospective studies in well defined pediatric patients are urgently needed to determine the value of serial Aspergillus PCR assays for the early diagnosis of invasive aspergillosis in children at risk.

Antigens, Fungal↗
PubMed2002

Risk of early febrile seizure with perinatal exposure to nucleoside analogues.

The frequency of seizures was studied in a prospective cohort of French children born to HIV-1-infected mothers. The analysis was restricted to the 4426 uninfected children, whether or not exposed to antiretrovirals. 81 convulsions were reported up to the age of 18 months, and 30 children fulfilled the criteria for simple febrile seizures. The risk of first febrile seizure was higher for children perinatally exposed to antiretrovirals than for those not exposed (log-rank test: p=0.0198). A similar trend was noted for other non-neonatal seizures (p=0.0537) but not for neonatal seizures.

Anti-HIV Agents↗
PubMed2002

[Hematologic manifestations of inborn errors of metabolism].

Haematological symptoms can be helpful for the diagnosis of metabolic diseases. A megaloblastic anemia orientates to folate and cobalamine anomalies when associated with homocystinemia and decreased plasma methionine levels, or to congenital oroticuria (hypochromia), Pearson syndrome (sideroblasts and vacuolisation of precursors) and thiamine transporter abnormality (sideroblasts) in the absence of homocystinuria. An hemolytic anemia orientates to anomalies of anaerobic glycolysis, heme synthesis, or iron metabolism, and Wilson disease. A pancytopenia orientates to organic aciduria, lysinuric protein intolerance, mevalonic aciduria and lysosomal storage diseases (Gaucher, Niemann Pick, Wolman) when hepatosplenomegaly is present. Uremic hemolytic syndrome and hemophagocytic lymphohistiocytosis respectively orientate to B12 anomalies, lysinuric protein intolerance, lysosomal storage diseases and organic aciduria.

Child↗
PubMed2002

PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection. Pediatric European Network for Treatment of AIDS.

OBJECTIVE: To produce European Guidelines for the use of antiretroviral therapy (ART) in HIV-infected children. DESIGN: Systematic literature review using Medline, the major antiretroviral conference reports, and IDSA recommendations on guideline production. SETTING: Pediatric European Network for Treatment of AIDS (PENTA) Steering Committee. OUTCOME MEASURE: Guidelines have been produced for the use of antiretroviral therapy in HIV-infected children in Europe. Recommendations on when to start ART and which ART to start, with dosages and a summary of the relevant literature, have been produced. CONCLUSIONS: These guidelines are aimed at assisting paediatricians in Europe with ART prescribing, and provide a more cautious approach to starting therapy than current paediatric USA guidelines.

Anti-HIV Agents↗
PubMed2001

Zidovudine genotypic resistance in HIV-1-infected newborns in the French perinatal cohort.

A retrospective study was set up to investigate the frequency of zidovudine (ZDV)-resistant HIV-1 in infected newborns after ZDV prophylaxis in the French Perinatal Cohort study. Nucleotide sequence analysis was carried out from 34 infants' isolates and 18 maternal plasma samples. Mutations related to ZDV resistance were found in the HIV-1 reverse transcriptase in 7 of 34 children (20%). Evidence of mother-child transmission of ZDV-resistant HIV-1 was found in 4 cases. Phylogenetic analysis showed that 14 of 34 HIV-1 isolates from the infants belonged to non-B subtypes. The presence of ZDV resistance-encoding mutations in the newborn isolates was associated with a longer total duration of exposure to ZDV. In a context of a wide HIV-1 variability, ZDV resistance can be one of the factors contributing to mother-child transmission.

Anti-HIV Agents↗
PubMed2001

Frequency and phenotyping of human immunodeficiency virus (HIV)-specific CD8+ T cells in HIV-infected children, using major histocompatibility complex class I peptide tetramers.

HLA-A*02 tetramers complexed to human immunodeficiency virus (HIV) Gag SLYNTVATL and HIV Pol ILKEPVHGV peptides were used to characterize HLA class I-restricted CD8(+) T cells in 41 HIV-infected children. The frequencies and the phenotype of specific circulating CD8(+) T cells were determined in whole-blood samples by means of cytometric analysis. Background staining of 13 HLA-A*02-negative patients showed that the frequency of CD8(+) T cells was <0.01%. Of the 28 HLA-A*02-positive patients, blood samples from 26 stained positive at least once the Gag tetramer (mean CD8(+) T cells, 0.87%; range, 0.1%-3.9%), and blood samples from 21 stained positive for the Pol tetramer (mean CD8(+) T cells, 0.59%; range, 0.1%-5.5%). The tetramer-binding cells were CD28(-), CD45RA(-), CD45RO(+), HLA-DR(+), and CD69(-) T lymphocytes. HIV-specific CD8(+) T cells can be detected easily in peripheral blood of HIV-infected children, using HLA tetramers combined with HIV peptides. These cells are memory activated CD28(-)CD8(+) T lymphocytes.

Adolescent↗