Search PubMed⌕ Search

Biomedical subjects

E Vilmer

Publications and source records attributed to E Vilmer.

At least 91 records · Page 5Linked to original sources
PubMed1996

Separation between HIV-positive women and their children: the French prospective study, 1986 through 1993.

OBJECTIVES: We studied the risk and circumstances of separation (due to either maternal death or drug use) between women infected by human immunodeficiency virus (HIV) type 1 and their children. METHODS: This analysis was based on the French Prospective Study of Infants Born to HIV-seropositive Women (1986 through 1993). Data recorded at each follow-up visit included the mother's effective presence with the child and the child's care after separation. RESULTS: A child's cumulative risk of long-term or permanent separation from his or her mother was 37% at 60 months. Maternal drug use was associated with an added risk during the child's first years (adjusted relative risk [RR]=3.4, 95% confidence interval [CI]=2.3, 5.0). The risk among drug users was even higher when the mother used injection drugs during pregnancy (adjusted RR=2.9, 95% CI=1.9, 4.3). Risk of early separation related to drug use tended to diminish since survey initiation. After separation, 57% of the children were placed through child welfare services and 43% were cared for by relatives. CONCLUSIONS: In the French Prospective Study, 2% to 3% of HIV-infected children were separated each year from their mothers as a result of the mothers death from acquired immunodeficiency syndrome (AIDS). Separations related to drug use have decreased over the years, and the family is becoming the most frequent carer after separation.

Actuarial Analysis↗
PubMed1996

Heterogeneity of B lineage acute lymphoblastic leukemias (B-ALL) with regard to their in vitro spontaneous proliferation, growth factor response and BCL-2 expression.

The spontaneous proliferation and the effects of 8 various growth factors (GF) were evaluated on leukemic cells from 27 patients with B-lineage ALL. Two groups of ALLs were distinguished. ALLs from group I (21 patients) exhibited a low spontaneous proliferative rate and were stimulated by IL-3 + IL-7 +/- SCF and/or LIF, while ALLs from group II (6 patients) had a high spontaneous proliferative rate and did no longer require this combination of GFs for proliferation. No effect of bFGF, IGF-I, IL-10 and IL-11 alone or in combination, was observed. Such differences in the behaviour of B-ALLs indicated that the GF requirement of ALL blasts was not related to the presence of serum in the culture nor to the pattern of reactivity of ALL blasts for B lymphoid markers or CD34 antigen. Furthermore, we showed in 1/9 cases that high proliferation might be due to an overexpression of the bcl-2 proto-oncogene and to the acquisition of an autocrine secretion.

Adult↗
PubMed1996

A low rate of loss of heterozygosity is found at many different loci in childhood B-lineage acute lymphocytic leukemia.

We have carried out a screening for loss of heterozygosity (LOH) in 51 children with B-lineage acute lymphoblastic leukemia (ALL). Forty-six highly polymorphic microsatellite markers located in subtelomeric areas of every chromosome arm were analyzed in each patient. Allelic losses were encountered at 21 of the 46 loci tested (46%). The frequency of LOH at a given locus was usually < 10% and fractional allelic loss, calculated as the ratio of chromosomal arms displaying loss among all informative arms for each patient, ranged from 0.025 to 0.31 (mean, 0.063). This study provides further evidence that deletional events are a major type of genetic alteration found in childhood ALL. The diversity of the loci displaying LOH suggests that, as in solid tumors, numerous tumor suppressor genes are likely to participate in leukemogenesis. However, the overall low frequency of LOH, as well as the absence of microsatellite instability suggest that the genetic instability is lower in childhood ALL than in most of the solid tumors.

Alleles↗
PubMed1996

Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42-43.

The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition, features of which are partial oculocutaneous albinism, increased susceptibility to infections, deficient natural killer cell activity, and the presence of large intracytoplasmic granulations in various cell types. Similar genetic disorders have been described in other species, including the beige mouse. On the basis of the hypothesis that the murine chromosome 13 region containing the beige locus was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained with the marker D1S235 (Zmax = 5.38; theta = 0). Haplo-type analysis enabled us to establish D1S2680 and D1S163, respectively, as the telomeric and the centromeric flanking markers. Multipoint linkage analysis confirms the localization of the CHS locus in this interval. Three YAC clones were found to cover the entire region in a conting established by YAC end-sequence characterization and sequence-tagged site mapping. The YAC contig contains all genetic markers that are nonrecombinant for the disease in the nine CHS families studied. This mapping confirms the previous hypothesis that the same gene defect causes CHS in human and beige pheno-type in mice and provides a genetic framework for the identification of candidate genes.

Animals↗
PubMed1996

Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Children's Leukemia Cooperative Group (CLCG).

Forty-six children with juvenile myelomonocytic leukemia (JMML) diagnosed between 1978 and 1993 in 12 centers were retrospectively studied. There is no evidence that any conventional treatment influences the long-term evolution of JMML. Among 28 patients treated without bone marrow transplantation (BMT), 26 died (median survival: 17 months), two are alive, one in complete remission (CR) after intensive chemotherapy. Allogenic BMT is the best treatment: 18 patients underwent BMT, 11 are in CR (at 9, 15, 22, 25, 41, 45, 49, 53, 66, 90 and 108 months). Conditioning regimens using chemotherapy alone may cure some patients (3/6) occasionally despite autologous reconstitution (1/3); if relapse occurs, a second BMT may be curative (2/3). Among the 12 patients conditioned immediately with TBI, six are in CR, one is in relapse, five died (one of them in durable autologus CR from Schwannoma). It is our opinion that splenectomy is of therapeutic value and seems not to have influenced the incidence of infections complications. We found no argument in favor of intensive chemotherapy before conditioning. Results with HLA-matched unrelated donors are satisfactory. One patient relapsed at 4 months after an unrelated BMT and entered a new CR after discontinuation of cyclosporine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Loss of heterozygosity in the chromosomal region 12p12-13 is very common in childhood acute lymphoblastic leukemia and permits the precise localization of a tumor-suppressor gene distinct from p27KIP1.

Abnormalities of the short arm of chromosome 12 are relatively common in hematologic malignancies and deletions of the region. 12p12-13 are found in approximately 5% of the patients with acute lymphoblastic leukemia (ALL). As a potent inhibitor of cyclin-dependent kinases, p27KIP1 prevents the progression of the cell cycle and the gene encoding p27KIP1 represents a potential tumor-suppressor gene. Its recent assignment to the chromosomal region (12p12.3) prompted us to study the p27KIP1 gene in a series of 61 children with ALL. Microsatellite polymorphic markers flanking the p27KIP1 gene were analyzed to detect losses of heterozygosity (LOH). Eleven patients displayed LOH for at least one of the markers. The deleted are encompassed the p27KIP1 gene locus in 10 cases, but inactivation of the remaining allele by deletion, translocation, or mutation was never observed. In addition, in 1 patient, the p27KIP1 gene was situated outside of the region of LOH. Thus, p27KIP1 does not seem to be the target gene of 12p12-13 alterations. However, this study indicates that 12p12-13 alterations at the molecular level, which are present in about 27% of the children with B-lineage ALL, are much more common than had previously been reported by usual chromosome analysis. Moreover, LOH mapping allowed us to better define the location of a putative tumor-suppressor gene implicated in these malignancies and should therefore help in identifying this gene.

Base Sequence↗
PubMed1995

Treatment of Chediak-Higashi syndrome by allogenic bone marrow transplantation: report of 10 cases.

Chediak-Higashi syndrome is a rare condition characterized by susceptibility to bacterial infections, defective natural killer activity, and episodes of macrophage activation known as accelerated phases. Chemotherapy can induce transient remission of the accelerated phase, but relapses become less and less sensitive to treatment and ultimately lead to death. Allogenic bone marrow transplantation (BMT) has been proposed as a curative treatment for Chediak-Higashi syndrome. We report the outcome of BMT in 10 such children. Seven received marrow from an HLA-identical related donor and three from an HLA-nonidentical related donor. Three patients died, two from a new accelerated phase after rejection of transplanted bone marrow and one from cytomegalovirus (CMV) pneumonia. Six of seven recipients of HLA-identical marrow and one of three recipients of HLA-nonidentical marrow are alive and well without treatment 1.5 to 13 years after transplantation (median, 6.5 years). No manifestations of accelerated phases have occurred in these seven patients, and significant natural killer activity is detectable. Interestingly, BMT prevented recurrence of accelerated phases in patients with limited numbers of donor-type leukocytes after transplantation. Ocular and cutaneous albinism were not corrected after transplantation. None of the patients developed serious toxic reactions to the BMT conditioning regimen or have long-term sequelae. These results show that HLA-identical BMT is an acceptable curative treatment for Chediak-Higashi syndrome, whereas HLA-nonidentical BMT remains an experimental approach.

Bone Marrow Transplantation↗
PubMed1995

Maternal factors associated with perinatal HIV-1 transmission: the French Cohort Study: 7 years of follow-up observation. The French Pediatric HIV Infection Study Group.

A nationwide, longitudinal study of infants born to human immunodeficiency virus-seropositive mothers has been under way in France since 1986. After 7 years of follow-up observations, we will update our assessment of the transmission rate in France and analyze, on a larger number of mother-infant pairs, the influence of maternal factors. Among the 848 pairs included in this analysis, the transmission rate was 20.2 +/- 2.7%. The transmission rate has remained stable with time and was not influenced by the mode of delivery, the mode of maternal infection, or the mother's ethnic origin. It was twice as high among the breast-fed infants as among the bottle-fed infants (40 vs. 19%, p < 0.04). Two factors were identified in a multivariate analysis (that did not include lymphocyte subset counts and the mode of feeding) as being associated with an increased risk of maternofetal transmission: p24 antigenemia (odds ratio = 3.1, confidence interval, = 1.5-6.2; p < 0.003) and elevated maternal age (p < 0.05). In the subgroup of 277 women whose absolute CD4+ lymphocyte counts at the time of delivery were available, the risk of transmission increased gradually from 15% of counts of > 600 CD4+ cells to 43% at counts of < 200. The risk of transmission was also related to the percentage of CD8+ cells, but each of the two factors seemed to play an independent role: the risk was lowest (12%) when the CD4+ cell count was > 500 and the proportion of CD8+ cells was < or = 40%, and was highest (50%) for values < 200 and > 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Interleukin-6 and interleukin-1 beta production in a pediatric plasma cell granuloma of the lung.

Plasma cell granuloma (PCG) is a pseudotumor of unknown origin. It is frequently accompanied by acute-phase clinical and biological signs that resume after complete surgical removal, suggesting production of soluble mediators. We therefore investigated the role of cytokines in a previously healthy 10-year-old boy with a PCG of the lung and systemic symptoms. In this case, very high serum levels of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were found before tumor excision, associated with inflammatory signs including major hyper-gamma-globulinemia. Pathologic analysis of the tumor showed an accumulation of fibroblasts and plasma cells producing immunoglobulins. Local production of IL-1 beta and IL-6 could be demonstrated at the messenger RNA (mRNA) level by the reverse transcriptase polymerase chain reaction and could be attributed to inflammatory cells by in situ hybridization and immunohistochemistry, whereas plasma cells exhibited membrane expression of the IL-6 receptor. Postsurgery follow-up showed rapid normalization of serum IL-1 beta and IL-6, whereas inflammatory protein levels decreased. This confirms the local production of cytokine within the PCG and raises the question of whether a dysregulation of cytokine production initiates the disease.

Base Sequence↗
PubMed1995

Randomly amplified polymorphic DNA analysis provides rapid differentiation of methicillin-resistant coagulase-negative staphylococcus bacteremia isolates in pediatric hospital.

Coagulase-negative staphylococci (CoNS) are now recognized as the most common cause of nosocomial bacteremia in pediatric patients. Randomly amplified polymorphic DNA analysis was used to study the relationships among 12 isolates of CoNS obtained from eight patients with catheter-related bacteremia in two distinct wards of our hospital and 6 epidemiologically unrelated strains. With this method, we were able to discriminate isolates that otherwise were indistinguishable by conventional criteria such as biochemical typing and antibiotic susceptibility patterns. Our results indicate that there were episodes of cross-infections among four patients in one ward but independent infectious episodes among four patients in the other ward. Randomly amplified polymorphic DNA analysis is a rapid method which seems particularly well suited to the epidemiological study of CoNS isolates.

Bacteremia↗
PubMed1995

[Cytomegalovirus retinitis in children with AIDS acquired through materno-fetal transmission].

PURPOSE: To describe the clinical feature and the outcome of CMV retinitis in children with vertically transmitted HIV infection. RESULTS: Five case-reports of cytomegalovirus retinopathy are described. These children from eight month-old to seven and a half year-old (median age at diagnosis 52 months) had been perinatally contaminated by the human immuno-deficiency virus. The ophthalmic signs included only a red eye for one patient. The clinical signs were similar to the adult's retinopathy. At the opposite the differences were emphasized like the clinical onset with a delayed diagnosis. Mean follow-up since diagnosis is 8 months with 3 patients still alive. CONCLUSION: CMV retinitis in vertically transmitted AIDS can occur early in childhood and must be checked systematically in the patients with low CD 4 count because of the usual asymptomatic onset.

AIDS-Related Opportunistic Infections↗
PubMed1995

Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia.

The immune response to leukemia is poorly understood. We postulated that nonmalignant T lymphocytes remaining within bone marrow from children with newly diagnosed ALL could be involved in this immune response. T lymphocytes which expressed gamma delta TCR comprised less than 1% of ALL marrow cells. A preferential outgrowth of gamma delta T cells within the CD3 population was observed when marrow cells were cultured with IL-2 alone or with stimulating feeder cells. These results, obtained in a series of 14 patients with precursor B-ALL, were significantly different when compared with expansions from normal marrow cells. In one patient, the clones established from the expanded population displayed different patterns of cytotoxicity against tumoral targets of the B cell lineage. Some clones expressing the TCR V delta 1 segment showed cytotoxic activity against a cell line derived from a pre-B ALL without activity against a LAK-sensitive B cell line. Using PCR amplification, one such clone was detected at high frequency, in the primary expansion of ALL marrow cells. These results suggest a prior activation in vivo of some gamma delta T cells by leukemic cells and provide some evidence on the role of these subsets in the immune response to leukemia.

Adolescent↗
PubMed1994

Thiopurine methyltransferase activity in a French population: h.p.l.c. assay conditions and effects of drugs and inhibitors.

1. Thiopurine methyltransferase (TPMT) is a cytosolic enzyme involved in the catabolism of thiopurine drugs, which are used to treat cancer patients and organ transplant recipients. Because TPMT activity is polymorphic and under genetic control, large interindividual variations in the immunosuppressive activity and toxicity of these drugs may, at least in part, be inherited. 2. We have developed a specific h.p.l.c. method for measuring 6-methyl mercaptopurine formed from 6-mercaptopurine (6-MP) in red blood cell lysates during the TPMT assay procedure. In blinded assays of 55 samples from adult blood donors, the results of the h.p.l.c. method correlated with those of the radiochemical reference method (r = 0.83, P < 0.001). 3. Using this h.p.l.c. assay, we tested the effect of known inhibitors of TPMT activity (syringic acid, p-anisic acid and tropolone) in vitro and showed that they were highly inhibitory. We also found that drugs often administered concomitantly with 6-MP (prednisone, prednisolone, 6-methylprednisolone, cyclophosphamide, methotrexate, and trimethoprim-sulphamethoxazole) had little or no effect on TPMT activity in vitro. 4. In a group of 300 French individuals, TMPT activity was highly variable, ranging from 4.7 to 35.3 nmol h-1 ml-1 of packed red blood cells (nmol h-1 ml-1 PRBC) with a mean value of 19.3 +/- 4.9. TMPT activity was not influenced by sex. 5. This sensitive and reproducible h.p.l.c. assay for TPMT activity in red blood cells may prove useful for prospective clinical studies designed to optimise dosage regimens of thiopurine drugs (detection limit for 6-methyl mercaptopurine is 5 ng ml-1, intra- and inter-assay variations are 6.8 and 8.2%, respectively).

Adult↗
PubMed1994

HLA-mismatched cord blood transplantation: immunological studies.

Two cases of HLA partially matched related cord blood transplantation were reported. The first patient remains healthy more than 4 years after graft. The second patient died from acute GVHD. In the first case, the immune reconstitution was studied over a 2 year period after graft: the alloreactive cytotoxic T-cell precursor (CTLp) frequencies were comparable between the donor and the recipient. Indirect evidence suggested that the resolution of GVHD was not due to a specific deletion of CTLp against the HLA antigens unshared between donor and recipient.

Child↗
PubMed1994

Donor B cell lymphoma of the brain after allogeneic bone marrow transplantation for acute myeloid leukemia.

We present a case of EBV-induced cerebral B cell lymphoproliferation of donor origin after HLA-matched allogeneic BMT for AML. The presentation was note-worthy as this 4-year-old girl was grafted after a conditioning regimen without irradiation, with an unmanipulated, HLA-matched graft. Furthermore, the cerebral mass developed long after reduction of immunosuppressive therapy following improvement of severe GVHD. To our knowledge, such cerebral lymphoproliferation, under these transplant conditions, has never been described.

Blotting, Southern↗