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Biomedical subjects

Y Bertrand

Publications and source records attributed to Y Bertrand.

At least 19 recordsLinked to original sources

l-folinic acid versus d,l-folinic acid in rescue of high-dose methotrexate therapy in children.

BACKGROUND: At this time, folinic acid (FA) is commercially available as the racemic mixture d,l-FA, whose biological activity is supported by natural l-FA. The administration of d,l-FA results in the accumulation of d-FA in plasma relative to the active l-FA form; in vitro studies have shown that d-FA can compete with the polyglutamation of methotrexate (MTX). PURPOSE: Our purpose was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture d,l-FA with the pure l-FA in rescue of high-dose MTX therapy (5 g/m2) in children with acute lymphocytic leukemia (ALL). METHODS: Eighteen children with ALL were entered in this trial, which was planned with a crossover design. Four cycles of MTX were administered to each patient, and rescue was achieved orally every 6 hours at a dose of 12 mg/m2 for d,l-FA and 6 mg/m2 for pure l-FA. The d,l-FA and l-FA rescues were alternated from one cycle to the next. d-FA, l-FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific high-performance liquid chromatography assay. RESULTS: Considering total active folate levels (l-FA + 5-MTHF), mean residual concentrations were similar for rescue by d,l-FA and l-FA, after two and six intakes, respectively: 92 and 186 nM for d,l-FA rescue versus 100 and 184 nM for l-FA rescue. Intra-individual comparison of total active folates (l-FA + 5-MTHF) did not show any significant difference between d,l-FA rescue and l-FA rescue. After administration of d,l-FA, the accumulation of d-FA in plasma was confirmed. For both types of FA rescue, MTX terminal half-lives were identical (average value, 13.9 hours). Considering each type of toxic effect (hematologic, hepatic, renal, and digestive), there was no significant difference in the proportion of toxic cycles following l-FA rescue or d,l-FA rescue. CONCLUSION: The administration of the pure l-FA, compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, leads to equivalent treatment tolerance, and avoids the plasma accumulation of d-FA.

Adolescent

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.

Actuarial Analysis

[Cerebrovascular accidents and sickle cell disease].

A 7 year-old girl, with homozygous sickle cell disease experienced two cerebrovascular strokes over an 8-month period. The diagnostic investigations were performed with highly sensitive imaging methods (MRI, angiography). Such a complication raises problems in curative and prophylactic treatment. New diagnostic methods are being evaluated.

Anemia, Sickle Cell

[Results and complications of induction treatment of acute leukemia in children. A personal series of 79 cases (1988-1989)].

In 1988 and 1989, 79 children have been treated for induction of acute leukemia. 68 presented an acute lymphoblastic leukemia (ALL) and 11 an acute non-lymphoblastic leukemia (ANLL). The complete remission rate was 92% (96% in ALL, 73% in ANLL). Fever occurred in 50% of the children, with positive blood cultures in 11 of them. One child died from streptococcal sepsis. No metabolic disorder was noted. Four patients were transferred into the intensive care unit. After 8 days, the treatment of ALL was continued in the outpatient clinic in more than 50% of the cases. The treatment of ANLL is frequently complicated by hemorrhages and sepsis and needs adapted supportive care in a specialized unit.

Adolescent

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

[Candida albicans arthritis during induction treatment of acute lymphoblastic leukemia].

Candida arthritis is a rare event which is a result of direct intraarticular inoculation, or--in compromised host--of hematogenous spread. We report on the case of an 18-month-old boy who experienced such an infection during induction treatment for acute lymphoblastic leukemia with aplastic onset. He was healed by daily systemic amphotericin B administered over a period of 3 wks associated with intravenous flucytosine during the first 2 wks; the treatment was continued with oral administration of ketoconazole for 5 wks. Treatment control was performed by drug monitoring in plasma and synovial fluid, as well as by determination of Candida antigenemia and antibody levels. We consider that the required doses of amphotericin B should be based upon plasma concentrations greater than 0.5 or 1 mg/l to be maintained during 2-3 wks. Providing that there is no resistance, the association with flucytosine may be useful.

Antifungal Agents

Comparison of HIV detection by virus isolation in lymphocyte cultures and molecular amplification of HIV DNA and RNA by PCR in offspring of seropositive mothers.

An early and accurate diagnosis of HIV infection is needed in the offspring of seropositive mothers. To this end, we have used two techniques for the direct detection of HIV in 12 newborns tested within 2 weeks after birth and 12 children. HIV isolation was carried out in lymphocyte cocultures and compared with detection of DNA and RNA sequences by molecular amplification using the polymerase chain reaction (PCR). In lymphocyte cocultures, HIV was isolated in 8 of 24 cases (33%), including 3 newborns, 3 symptomatic children, and 2 asymptomatic ones. HIV DNA was detected by PCR in twice as many cases, i.e., in 16/24 cases (66%), including 7/12 newborns, 4/4 symptomatic children, and 5/8 asymptomatic ones, 2 of whom became seronegative, HIV RNA was detected in 10 of 16 cases (60%) with detectable HIV DNA, including all of the cases who had a positive HIV isolation. Only children with clinical or biological signs of HIV infection were positive for HIV RNA. Furthermore, signs of HIV infection appeared within 6 months in three of the four newborns who were positive for HIV RNA at birth. These results indicate that HIV DNA detection by PCR is far more sensitive than HIV isolation in culture for the early diagnosis of HIV infection in offspring of seropositive mothers. HIV RNA detection appears to be a useful prognostic marker since it does correlate with disease progression and may serve as a clue for HIV replication in vivo.

Cells, Cultured

Exercise induces pentane production and neutrophil activation in humans. Effect of propranolol.

The effect of beta-adrenergic receptor blockade on exercise-induced lipid peroxidation in man has been examined by measuring the production of pentane in expired air. For this purpose, five healthy male subjects were subjected to dynamic exercise of graded intensity on a cycle ergometer (10 min at 45%, 5 min at 60% and 75% maximal oxygen uptake 1 h after ingestion of either a placebo or 40-mg propranolol. At rest, mean pentane concentration [( pent]) with placebo was 4.13 pmol.l-1, SD 2.14. After exercise, this value significantly increased by 310% (17.1 pmol.l-1, SD 7.73, P less than 0.01). Oral administration of 40-mg propranolol significantly lowered the mean resting [pent] to 1.75 pmol.l-1, SD 0.77, P less than 0.05. After exercise, the increase of [pent] was much smaller (240%) and was less significant (P less than 0.2) than with the placebo. The mechanism of this inhibitory effect of propranolol remains to be elucidated. However, as indicated by the measurement of plasma myeloperoxidase concentration, it can be concluded that the antioxidant property of propranolol cannot be attributed to the inhibition of neutrophil activation, a possible source of free radicals during exercise.

Adult

[Transfusion of concentrates enriched in neocytes in the thalassemic child. Preliminary results].

In this study, we compared the results of young red cells transfusion for 12 months with the administration of conventional red cells units during the year before, in three thalassemic children. We used the Neocel system (Cutter laboratories) to prepare neocytes. A quality control of neocyte units was developed: especially the phthalate oil technique which shows a 70% enrichment of young red cells. These patients received 170.4 +/- 9 ml/kg of body weight of neocytes compared with 197 +/- 20 ml/kg of body weight of conventional red cells concentrates. The mean decrease of hemoglobin transfused per kg of body weight per year was 22%. The mean pretransfusion hemoglobin level did not change during the 2 years of study. The children grow without any problem and no pathologic event occurred during the study. The control of the serological ferritin levels does not allow for definitive conclusions in the evolution of the iron overload of our three patients. However, this overload seems to decrease. It's why it's necessary to carry on with our study.

Blood Transfusion

[Granulocytic sarcoma (chloroma): rare extramedullary tumors associated with acute non-lymphoblastic leukemia].

The authors report 5 new cases of pediatric granulocytic sarcomas. These rare extramedullary tumors are composed of immature granulocytic cells, usually associated with an acute non lymphoblastic leukemia, but may appear several months before. Their characteristics are exposed (epidemiology, clinical features, cytology and cytogenetics), and therapeutic rules are discussed, especially for the granulocytic sarcomas without evidence of bone marrow involvement. The prognosis is known to be poor.

Child, Preschool

Differences in tocopherol-lipid ratios in ARDS and non-ARDS patients.

Plasma tocopherol, plasma total lipid levels and tocopherol-lipid ratio were measured every 6 h during 48 h in 12 critically ill patients and compared with those of a control group. The patients were divided into two groups. Group I comprised 6 critically ill patients with ARDS and group II comprised 6 severely ill patients without ARDS. The means for all observations of plasma tocopherol, total lipid levels and tocopherol-lipid ratio in groups I and II were significantly depressed relative to a control group (p less than 0.0001). The difference in the average tocopherol-lipid ratio between the three groups (p less than 0.0001) and between the groups I and II was statistically significant (p less than 0.0001). Our results indicated: (1) a decrease of vitamin E concentrations in the critically ill patients, particularly in ARDS patients; (2) the importance of the relationship between plasma tocopherol and plasma lipids levels in evaluating the deficiency in vitamin E which was evident in ARDS patients.

Adult

[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

[Treatment of vaso-occlusive crisis of sickle-cell disease with pentoxifylline].

Sickle-cell disease is usually complicated by vaso-occlusive attacks. A review of the case-histories of 26 patients permitted an analysis of 92 severe attacks. We compared the outcome of 52 attacks treated with hyperhydration associated with a modifying erythrocyte membrane agent (pentoxifylline), with 40 attacks treated with hyperhydration and other drugs. This result compares well the current knowledge of the rheologic mechanisms involved in vaso-occlusive attacks of sickle-cell disease.

Adolescent