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Biomedical subjects

N Philippe

Publications and source records attributed to N Philippe.

At least 19 recordsLinked to original sources

Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors.

In the present study, we have investigated the effects of IL-4 on the proliferation and differentiation of leukemic and normal human B cell precursors (BCP). We have demonstrated that IL-4 significantly inhibited spontaneous [3H]thymidine ([3H]-TdR) incorporation by leukemic blasts from some B lineage acute lymphoblastic leukemia (BCP-ALL) patients (8 of 14). Furthermore, IL-4 was found to suppress the spontaneous and factor-dependent (IL-7 and IL-3) proliferation of normal BCP (CD10+ surface [s] IgM- cells) isolated from fetal bone marrow. Maximum growth inhibition of either leukemic or normal BCP was reached at low IL-4 concentrations (10 U/ml), and the effect was specifically neutralized by anti-IL-4 antibody. IL-4 was further found to induce the expression of CD20 antigen on BCP-ALL cells from a number of the cases examined (5 of 8), but in contrast to leukemic cells, IL-4 failed to induce CD20 antigen on normal BCP. Finally, IL-4 was found to induce neither the expression of cytoplasmic mu chain, nor the appearance of sIgM+ cells in cultures of normal or leukemic BCP. Our data indicate that IL-4 has the potential to inhibit cell proliferation in leukemic and normal human B lymphopoiesis but is unable to drive the transition from BCP to mature B cells.

Antigens, CD

[Acute lymphoblastic leukemia in children: which prognostic factors in 1992?].

Considerable advances were made during the Eighties in the treatment of acute lymphoblastic leukemia in children, using an intensive treatment regimen. The impact of numerous diagnostic variables on the prognosis has been modified; their re-evaluation as prognosis factors is necessary. Great importance is now attributed to the appreciation of the tumor burden, to the immunophenotype, and most importantly to cytogenetic data. This paper describes the prognosis factors currently used to define risk-group, and risk-adapted treatment regimen.

Child

[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

[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

Assignment of Sp alpha I/74 hereditary elliptocytosis to the alpha- or beta-chain of spectrin through in vitro dimer reconstitution.

Partial digestion of spectrin dimers in vitro has allowed the definition of domains. For example, the portions of the dimers that are involved in spectrin self-association are represented by the alpha I and the beta I domains. The alpha I domain (80 Kd) is further cleaved into a minor 78 Kd fragment and, more substantially, into a 74 Kd fragment. The intensity of the latter, which we expressed as the 74:(80 + 78 + 74) ratio, or the 74:alpha I ratio, is variable depending on the experimental conditions, eg, in fine, on the conformation of the alpha I domain. A number of cases of hereditary elliptocytosis (HE) are associated with an increase of the 74:alpha I ratio, also referred to as the Sp alpha I/74 abnormality. Several lines of evidence have suggested that the causal mutations may lie in the alpha- or the beta-chain, a point of importance before one undertakes studies at the gene level. In order to address this question, we reconstituted spectrin dimers in vitro, combining alpha- and beta-chains of various origins, and then carried out partial digestion and assayed the Sp alpha I/74 abnormality. The patterns obtained with reconstituted dimers were nearly identical to those of native dimers. We applied the assay to three spectrin variants that cause Sp alpha I/74 HE: (1) a variant that we previously designated spectrin Nice and whose beta-chain lacks a 4 Kd fragment in its C-terminal region; and two distinct variants that we found in two unrelated white families and that we provisionally designated spectrin Lyon and spectrin Culoz. The Sp alpha I/74 abnormality appeared in all kinds of dimers that harbored the beta-chain of spectrin Nice, or the alpha-chain of spectrin Lyon or spectrin Culoz, respectively. Therefore, we confirmed that spectrin Nice is a (alpha I/74) beta-variant, and established that both spectrin Lyon and spectrin Culoz are (alpha I/74) alpha-variants. The present assay may be extended to any spectrin variant displaying the Sp alpha I/74 abnormality.

Adolescent

[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

Cell kinetics in acute lymphoblastic leukaemia: comparative analysis between adults and children.

Cell kinetics were studied in 124 patients with acute lymphoblastic leukaemia (ALL) by flow cytometry, comparing cell cycle characteristics between adults (57 cases) and children (67 cases). S, G2 + M and the low protein content fraction of G1 (LPC fraction) were determined and studied in relation to other clinical and biological features. No difference was found between adults and children in the distribution of these variables. The proliferative rates according to organomegaly, leukocytosis, the FAB cytological groups and the immunological groups did not present any significant differences between the two groups of patients. However, cell cycle did seem to have a very different prognostic value for adults and for children. G2 + M was a strong prognostic indicator for childhood ALL: duration of CR and survival were significantly longer when G2 + M was higher (P less than 0.01). In adults, survival was longer for intermediary (between 3.8 and 5.8%) and high (over 7.2%) G2 + M values (P less than 0.01). The negative correlation between S and G2 + M observed in adults and the absence of correlation in children raise the possibility of differences in duration of the different phases for the two groups and perhaps an accumulation of cells in G2 or tetraploidy in some cases.

Adolescent

[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