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Biomedical subjects

G Leverger

Publications and source records attributed to G Leverger.

At least 127 records · Page 7Linked to original sources

Quantitative blood cultures for diagnosis and management of catheter-related sepsis in pediatric hematology and oncology patients.

Paired quantitative blood cultures collected simultaneously via catheter and peripheral vein in Isolator 1.5 ml tubes, were performed in 50 febrile hematology children. Samples were taken to diagnose catheter-related sepsis (CRS) without catheter removal and to monitor the therapeutic efficiency of antimicrobials administered through the infected device by infusion and/or by the antibiotic lock technique (ALT). In 7 children (14%) the colony counts from catheter blood samples were 30-fold higher than the colony counts from peripheral samples, suggesting CRS; in 7 other patients (14%), identical colony counts in both samples suggested sepsis was not catheter-related. One patient (2%) had septicemia caused by E. coli found in the urinary tract; only the peripheral blood cultures were positive. In 6 patients (12%), the Isolator system was not effective for diagnosing bacteremia or CRS; in 29 patients (58%) the febrile episode was not microbiologically documented. All episodes of CRS were cured whatever the treatment was: infusion or ALT.

Anti-Bacterial Agents↗

A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.

Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.

Adolescent↗

Study of tolerance and effectiveness of a varicella vaccine in leukemic children.

Chickenpox could be a severe disease in immunocompromised patients. Live attenuated vaccine is now available. We conducted a trial in 37 leukemic children with OKA varicella vaccine. Full immunization was observed in all 20 seronegative patients. Few side effects and no generalized vaccinal infection were observed. Further studies are warranted to assess the benefit of vaccination in leukemic patients considering the effectiveness of Varicella Zoster Immuno-Globulins and Aciclovir.

Adolescent↗

[Lead poisoning in children. Apropos of 129 cases].

One hundred and twenty nine children with chronic lead poisoning were followed from August 1985 to July 1989. Old lead paint was recognized as the contaminant source at home. Pica of paint flakes was the main mode of intoxication. Children were classified according to the Center for Disease Control 1985 as follows: class IV (39 cases), class III (45 cases), class II (30 cases), class I (15 cases). Nineteen of those in class IV had blood lead levels above 700 micrograms/l and received BAL + EDTA followed by EDTA alone for a mean of 4.6 +/- 3.5 courses. With this treatment, blood lead level decreases were 50 +/- 17%. Nine of these class IV children had an evaluation at last 3 months after the last chelation course: 5 became class I or II, and 2 class III with a negative provocative test. The remaining 20 children in class IV were given a mean of 2.7 +/- 1.4 courses of EDTA. Blood lead levels decreased by 52 +/- 15%; 11 children were evaluable at least 3 months after the last chelation course: 4 became class I, and 7 class II. Thus overall 80% of class IV moved under treatment to class I or II. Among those 45 children in class II, 30 underwent a provocative test and 24 one to three courses of EDTA: 8 were further studied: 3 became class I and 5 class II. Combination of screening, medical treatment and sociocultural approach led to avoid acute effects of severe chronic childhood lead poisoning. The efficacy of such an approach in preventing chronic effects has still to be evaluated.

Chelating Agents↗

Use of oligonucleotide probes directed against T cell antigen receptor gamma delta variable-(diversity)-joining junctional sequences as a general method for detecting minimal residual disease in acute lymphoblastic leukemias.

To provide a sensitive and generally applicable method to detect clonal cells in acute lymphoblastic leukemias (ALL), we have designed a new strategy based on the polymerase chain reaction (PCR) amplification of the T cell receptor gamma delta gene rearrangements found in most T and B lineage ALLs. PCR allows rapid sequencing of variable-(diversity)-joining (V-[D]-J) junctions from tumor DNA and construction of anti-junctional oligonucleotides (AJOs) used as probes to detect clonal cells in the same patient. We have defined oligonucleotides suitable for all T cell receptor (TCR) rearrangements involving functional V gamma segments. Oligonucleotides corresponding to preferential TCR delta rearrangements in T and B lineage ALLs were also used. By analysis of the nucleotide sequence of 52 V gamma-V gamma junctions from 30 cases of B and T ALLs, we demonstrate that V-J junctional sequences are clone specific in both lineages and at all stages of differentiation examined despite the frequent presence of the recently described P nucleotides. Experiments performed with TCR gamma delta AJOs on DNA from tumor cells and polyclonal T cells show that AJOs can be used to differentiate clonal cells from polyclonal T cells, distinguish between different T cell clones, and detect residual clonal populations at 10(-4)/10(-5) dilution. AJOs were also used to detect residual disease in samples from patients in clinical and morphological complete remission. Finally, rearrangement patterns were studied by classical Southern analysis in selected cases at both presentation and subsequent relapse showing absence of clonal evolution in most cases. V-(D)-J nucleotide sequences of rearrangements with an identical pattern of rearrangement at presentation and relapse were identical in all cases analyzed. We therefore describe a new, specific, and clinically useful strategy for the detection of minor clonal populations applicable in the majority of cases of ALL.

Alleles↗

[Efficacy of the combination of ceftazidime/vancomycin in the first line treatment of infection in neutropenic children].

UNLABELLED: Infection is the first reason of mortality in children with bone marrow aplasia. It justifies the immediate treatment initiation before bacteriological cultures results. First line probabilistic treatment must have a bactericidal activity on the pathogens and must be atoxic. The empirical therapy consisted of ceftazidime 100 mg/k/d and vancomycine 40 mg/k/d three times a day. We treated 41 patients, ranged from 0.5 to 17 years (mean 9.5 years). 27 lymphoblastic leukaemias, 10 myeloblastic leukaemias, 4 lymphomas, presenting post therapeutic prolonged aplasia: PMN less than 500/mm3. 23 strains were isolated from 15 patients. 12 Gram+: 7 ceftazidime sensitive, 12 vancomycine sensitive and 11 Gram-: 10 ceftazidime sensitive. Only one is resistant to ceftazidime + vancomycine. Apyrexia was obtained in less than 48 hours in 36 patients. Mean treatment duration was 16 days. Hyperthermia relapsed 17 times and was susceptible to ampho B ten times, although no candida was isolated. When ceftazidime + vancomycine combination failed, other antibiotic treatment was ineffective. There were 4 superinfections (2 in blood, 1 enteric, 1 pharyngeal) and 2 germs were ceftazidime resistant. IN CONCLUSION: ceftazidime + vancomycine combination is a very effective treatment of infection in the neutropenic children: 88% success. 95% of the germs are sensitive to, at least, one of the 2 antibiotics. There are very few superinfections. Tolerance is excellent.

Adolescent↗

Monosomy-7 in childhood hemopoietic disorders.

Acquired pure monosomy-7 is associated with various myeloproliferative disorders (MPD), myelodysplasias (MDS), and acute myeloblastic leukemias (AML) in children and a poor prognosis. A series of 14 malignant blood disorders with pure monosomy-7 in children (eight MPD, two refractory anemia with excess of blasts, (RAEB), and four AML) is reported and compared with cases in the literature. The median age is significantly different in the patients with MPD and those with MDS or AML: 23, 80.5, and 112 months, respectively. The outcomes of MPD and RAEB are characterized by a high risk of rapid blastic transformation and resistance to polychemotherapy. Bone marrow transplantation (BMT) seems to be the best treatment, and one survival of two years in complete remission after autologous BMT in a child with AML is reported. Several myeloid cell lineages are involved in the proliferation, which partly explains the difficulties of cytologic classification and suggests that a pluripotent stem-cell is at the origin of the disease.

Adolescent↗

Delayed renal failure with extensive mesangiolysis following bone marrow transplantation.

Within two years we have had the opportunity of observing seven leukemic children who were referred to our Pediatric Nephrology Unit for delayed renal failure following bone marrow transplantation (BMT). These children (3 to 12 years old), six with acute lymphoblastic leukemia (ALL) and one with acute non-lymphoblastic leukemia (ANLL), underwent BMT (4 autologous BMT, 3 allogeneic BMT) after the first remission in two, and after the second remission in five. Preparative regimen for BMT included cyclosphosphamide in three, cyclosphosphamide, vepeside and cytosine A in four, and a total body irradiation in a single dose of 10 grays (1000 R) in all of them. Three children were treated immediately after grafting with low dose cyclosporine for four to six months. Five to 10 months after BMT, four patients developed a hemolytic uremic syndrome with severe hypertension. The remaining three were found to have isolated renal insufficiency several months post-BMT. In the seven patients, renal biopsy showed a uniform pattern of severe glomerular involvement characterized by extensive lesions of mesangiolysis associated with severe arteriolonecrosis. A repeat biopsy performed one year later, in two patients showed severe scarring of the renal parenchyma with minor lesions of mesangiolysis. The similarity of the pathologic features observed suggests that the same mechanism might have been operative in the seven patients. It is very likely that the nephropathy is related to total body irradiation enhanced by chemotherapy. We conclude that current treatments of high risk leukemia might become a new cause of chronic renal failure. Further investigations are needed to know the exact incidence of this complication.

Bone Marrow Transplantation↗

Bone marrow transplantation for genetic and metabolic disorders.

Bone marrow transplantation (BMT) was primarily used for the treatment of hematologic malignancies and aplastic anemias. BMT has been successfully applied as curative treatment in a series of lethal congenital disorders but among more than 1000 inherited metabolic diseases only 20 of them can be corrected by transplantation. The inborn error must be expressed in the stem cells. The genetic disorders that can be cured include congenital immune deficiencies, osteopetrosis, and congenital lysosomal storage diseases, mucopolysaccharidosis and lipidosis. BMT with an HLA matched donor is successful in 60% of patients with severe combined immune deficiency and Wiskott Aldrich syndrome. Results are good in osteopetrosis if BMT is performed early. Encouraging results have been reported in Hurler disease and in Gaucher disease.

Bone Marrow Transplantation↗

[Parvovirus infections in children with hemolytic anemia].

Acute episodes of erythroblastopenia in children with chronic hemolytic anemias have been recognized for a considerable length of time. In 1981, a small virus with a single strand of DNA, parvovirus B 19, was identified as the causative agent in most such episodes. Other diseases have been ascribed to parvovirus B 19, including erythema infectiosum or fifth disease, polyarthralgia, fetal death. Schonlein-Henoch disease, and bone marrow aplasia. In acute attacks of erythroblastopenia, anemia is the most prominent manifestation, but coexistence of neutropenia and thrombopenia has been reported. Hematologic disorders last for approximately ten days. The diagnosis of recent parvovirus B 19 infection rests on detection of specific IgM antibodies, or direct visualisation of the virus by electron microscopy. More recently, detection of the viral genome using molecular hybridization techniques has been achieved. In vitro studies have confirmed the inhibiting effect of parvovirus B 19 on red cell line progenitors, particularly CFU-E, but the exact mechanism of the inhibition remains uncertain. Other diseases due to parvovirus B 19 or other parvoviruses probably remain to be discovered.

Anemia, Hemolytic↗