Mitochondrial macro-haplogroup JT may play a protective role in ovarian ageing.

This study of 200 Caucasian women shows that the distribution of the mtDNA macro-haplogroups in patients with diminished ovarian reserve (DOR) differed significantly from that of patients with normal ovarian reserve (NOR) (p=0.02). The JT macro-haplogroup was significantly under-represented in DOR patients compared with NOR patients (p=0.006) and compared with the estimated frequency of 18.8% in the general French population (p=0.0012). Our findings suggest that the risk of a prematurely depleted ovarian reserve would be three times lower for patients carrying the JT macro-haplogroup than for patients with any of the other mtDNA haplogroups (odds ratio: 0.3; 95% CI: 0.13-0.74). If these preliminary results are confirmed in larger independent studies, they should lead to the better management of infertility.

[Molecular characterization of corona radiata cells from patients with diminished ovarian reserve]. / Profil d'expression des cellules de la corona radiata chez les patientes présentant une réserve ovarienne diminuée.

OBJECTIVES: Diminished ovarian reserve (DOR) is one of the causes of infertility. In this prospective study, gene expression profiling (GEP) of corona radiata cells (CRC) was performed to identify genes deregulated in DOR patients. PATIENTS AND METHODS: Microarray-based GEP of CRC isolated from eight women undergoing IVF was performed to identify genes differentially expressed between patients with normal ovarian reserve and DOR patients. Microfluidic-based quantitative RT-PCR assay were used to validate selected transcripts on 40 independent patients. RESULTS: Forty-eight transcripts were differentially expressed, including CXXC5 and FOXC1 down regulated in DOR, as well as CTGF, FSTL3, PTGS2 and SOCS2 up regulated in DOR. According to these transcripts, two DOR patients'subgroups (DOR Gr1 and Gr2) were identified. In DOR Gr2 patients, CITED2, CTGF, GAS-1, IRS2, PTGS2, SOCS2, VCAN were expressed at significantly higher levels, and CXXC5, FOXC1, GBP2 and ZMIZ1 at significantly lower level. Eleven of those genes are transcriptional targets of Estrogens and higher baseline oestradiol levels were observed in DOR Gr2 patients (P<0.006). DISCUSSION AND CONCLUSION: Twelve genes deregulated in CRC of DOR patients were identified, which could be involved in DOR pathogenesis. The distinction of a particular subgroup of DOR patients suggests the possibility of deregulation of estrogen response genes.

[The first consultation with an adolescent]. / La première consultation avec un adolescent.

It is crucial not to miss the first consultation with an adolescent. This article reviews some of the essential step necessary to help make the first consultation a success: the time to devote to the patient, the preparation of the consultation, mandatory issues to address, clinical/physical examination, conclusion of the consultation, the prescriptions and the follow-up.

[Doppler waveforms patterns of vascular anastomoses in monochorionic twin pregnancies. A report of three cases and review of the literature]. / Mise en évidence des anastomoses vasculaires par la vélocimétrie doppler dans les grossesses gémellaires monochoriales. Revue de la littérature à propos de trois cas.

Three cases of intermittent absent end-diastolic and reversed end-diastolic flow velocity (A/REDV) are reported in the proximal umbilical artery of the growth-retarded twin in monochorionic twin pregnancies. This typical doppler velocimetric pattern has been related to arterio-arterial anastomoses in two cases of intra-uterine growth retardation and in one case of twin-twin transfusion syndrome. According to the literature, superficial arterio-arterial anastomoses may be detected by doppler colour velocimetry in 75 to 85% of cases, while identification of arteriovenous connections is more difficult to be documented in vivo (50% of cases in experienced hands). The role of superficial vascular anastomoses, either arterio-arterial or venovenous, and that of deep arteriovenous communications is now well documented in the main complications of monochorionic pregnancies, particularly for twin-twin transfusion syndrome, intrauterine growth retardation, intrauterine fetal death and acardiac twins.

Predictive factors of post-discharge follow-up care among adolescent suicide attempters.

OBJECTIVE: To study short-term compliance with follow-up care in a sample of adolescent suicide attempters. METHOD: One hundred and sixty-seven adolescents, aged from 13-18 years and hospitalized after a suicide attempt, completed a questionnaire that included the CES-Depression Scale and Zung Anxiety Scale. Physicians assessed the hospital care immediately after the attempt, and post-discharge care plans. Three months later, adolescents were contacted by telephone and asked about follow-up care. RESULTS: After 3 months, 91.6% of the adolescents could be contacted: 25.5% never attended any follow-up; 11.1% went only once; 31.4% missed some appointments; and 32.0% went to all their scheduled appointments. Adolescents who complied with follow-up care differed significantly from those who did not: they showed more depression, anxiety and illicit drug use at the time of the attempt; they had more often planned the attempt; they were hospitalized longer; and they met with a psychiatrist more often while hospitalized. Compliance was also better when the follow-up appointment was scheduled before discharge. CONCLUSION: Compliance with post-discharge follow-up care depends upon the adolescent's psychopathology but may also be improved by the type of hospital care and post-discharge plans.

Pharmacokinetics of itraconazole oral solution in neutropenic children during long-term prophylaxis.

We investigated the pharmacokinetics and safety of an oral solution of itraconazole in two groups of neutropenic children stratified by age. Effective concentrations of itraconazole in plasma were reached quickly and maintained throughout treatment. The results indicate a trend toward higher concentrations of itraconazole in plasma in older children.

[Secrecy in children with HIV infection]. / Le secret chez les enfants infectés par le VIH.

The secrecy surrounding the disease of parents and children infected with HIV leads to psychic and affective isolation and difficulties of communication within the family. Psychological management may possibly help to resolve the problem of secrecy between parents and children. We analyzed the organization and dynamics of the secret surrounding children contaminated by their mothers. The analysis was prospective and was based on semi-directive interviews and drawings. We followed up, over a period of two years, ten children (mean age: 4 years, range: 4 months to 12 years) with different ethnic and socio economic backgrounds. In each family, the child was the target of the secret, the pediatrician the guardian, and the mother (or her substitute) the keeper. The organization of the secret around the other potential guardians varied from one family to another. Two modes of intra-family communication were observed: the secret (reserved for the youngest children) and the tacit. One child suffered from a disorder related to the secret, the others had depressive and reactional symptoms. At the end of the study, the manner of approaching, and especially dealing with, the question of the secret had changed appreciably in each family: disclosure to the family circle (three cases), passage of the child from the secret to the tacit (two cases), and easier questioning of the pediatrician in all of the cases. Nonetheless, in no case had the secret been completely lifted for the child. Four children asked to continue psychological management. The changes in the dynamics of the secret and the appeasement observed in the families suggest that psychotherapeutic aid should be offered to families where a child has been contaminated with HIV by the mother.

[Sickle cell anemia: study of the pediatric mortality in Ile de France from 1985 to 1992]. / Drépanocytose: étude de la mortalité pédiatrique en Ile de France de 1985 à 1992.

BACKGROUND: Sickle cell anemia is now relatively frequent in France. Its clinical course is punctuated by acute episodes that threaten the life, specially during the first year of life. POPULATION AND METHODS: The files of 26 children (14 boys, 12 girls) dead from sickle cell disease between 1985 and 1992 were retrospectively studied. These files concerned patients from the Ile-de-France area. RESULTS: Their mean age at time of diagnosis was 13.7 months (0 to 3 years 4 months); mean age was 5.5 years at time of death. Infection was the cause of death in 15 patients (S pneumoniae in eight patients despite prophylactic penicillin and pneumococcal vaccine in the majority of them). Splenic sequestration crisis was the cause of death in three patients less than 5 years of age; vasocclusive crisis resulting in cerebral infarction was the cause in three patients aged 7.5 to 13 years. Mortality calculated from those patients followed since 1987 (total: 2,063 years) was 0.29% person/year. CONCLUSION: Comfort of patients and risk of permanent disability become the main factors of choice for new treatments such as chemotherapy or bone marrow transplantation.

Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study. French Society of Paediatric Haematology and Immunology.

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as 'primary' (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the fur girls studied exhibited a polyclonal pattern of X-inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues. This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.

Successful engraftment after autologous transplantation of 10-day cultured bone marrow activated by interleukin 2 in patients with acute lymphoblastic leukemia.

Disease recurrence remains the major problem in autologous bone marrow transplantation (BMT) for hematologic malignancies. To improve the therapeutic efficiency of autologous BMT, we investigated the use of autologous marrow activated in vitro with interleukin 2 (IL-2) to generate killer cells for in vivo purging. A feasibility trial was initiated in 5 patients with poor prognosis acute lymphoblastic leukemia, who were transplanted, after marrow ablative therapy, with autologous marrow cultured for 10 days with 10(3) units of IL-2/ml. A highly significant increase in NK activity and an induction of LAK activity were observed after incubation. Patients received 0.64 to 1.56 X 10(8) cultured BM cells/kg and 1.87 to 44.8 x 10(4) CFU-GM/kg. Four patients engrafted and achieved granulocyte counts > 0.5 x 10(9)/l on days 35, 24, 36 and 22 after transplant. Three of these patients showed platelet recovery to > 50 x10(9)/l on days 25, 42 and 40 after transplant. One patient remained thrombocytopenic until relapse. One patient died on day 12 after transplant. This study demonstrates that cultured BM activated with IL-2 can be used successfully for hematological rescue in the clinical setting.

[Erythrocytosis in a 4 year-old child: diagnostic, prognostic, therapeutical problems]. / Erythrocytose pure chez un enfant de 4 ans: problèmes diagnostiques, pronostiques, thérapeutiques.

BACKGROUND: Pure erythrocytosis is rare in children. This report describes such a case. CASE REPORT: A 4 year-old boy was admitted because erythrocytosis had been found routinely before adenoidectomy. He was born in Guatemala, was adopted just after his birth, and had been living in France since that age. Clinical examination was normal. His hemogram showed: erythrocytes: 8,800,000/mm3; hemoglobin: 20.1 g/dl; hematocrit: 66.8%; reticulocytes: 262,000/mm3; platelets: 200,000/mm3; leukocytes: 6,800/mm3. The patient had been given iron salts for the past 3 months without an earlier hemogram. Total red cell mass was 1200 ml (N: 600). The myelogram was normal as was the leukocyte alkaline phosphatases, serum lysozyme and vitamin B12. Blood ferritin was low (3.5 ng/ml). In vitro cultures of erythroid precursors were normal, as was the karyotype of myeloid cells. Blood erythropoietin concentration was 20-293 mU/ml (N:4-14). All the causes of secondary polycythemia were eliminated by appropriate investigations. The patient was treated by phlebotomy in aliquots of 25 ml/kg, twice a month, for 10 months, and was given iron therapy. At the end of treatment, his hemoglobin was 14 g/dl and his hematocrit was 45%. Both progressively increased again one year later, requiring new phlebotomies. The patient was followed for 4 years but no cause for this erythrocytosis was found; it was probably congenital in origin. CONCLUSION: This case of pure erythrocytosis was associated with elevated erythropoietin production. Whether this high secretion is related to receptor dysfunction remains to be determined.

A case of peroxidase-positive acute leukaemia expressing only T lineage lymphoid markers.

We report the clinical presentation and the morphological, immunophenotypic, cytogenetic and molecular genetic characteristics of a 14 1/2-year-old boy who had French-American-British (FAB) type M1 acute non-lymphocytic (ANLL) leukaemia with a common T-ALL immunological phenotype, with no myeloid associated antigen, either on the membrane or in the cytoplasm. ALL-directed induction therapy induced complete remission.

Treatment of relapsed or refractory acute leukemia in childhood with bisantrene combined with high dose aracytine.

Bisantrene is an anthracene derivative which has demonstrated activity in acute myeloblastic leukemia (AML) and in lymphoma. The present study was designed to assess the reinduction rate and toxicity of bisantrene (250 mg/m2/d x 5) associated with aracytine (100 mg/m2 twice a day x 5) in refractory and relapsed acute childhood leukemia. Patients who relapsed after bone marrow transplantation were eligible. Twenty-six children were included. Diagnoses were as follows: 13 AML, 9 acute lymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL). All patients had been very highly pretreated, especially with anthracyclines, and most of them were of poor prognosis. The overall response rate was 46% with a 95% confidence interval ranging from 27-65%. According to diagnosis, complete remission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four children died, three from infection and one from acute lysis syndrome. The major toxicity was infection with grade 3 and 4 episodes occurring in 42% of patients. No significant cardiac toxicity was noted. Hepatic and renal toxicity was noted. Hepatic and renal toxicity were limited and transient. Bisantrene in association with aracytine is effective in both AML and ALL of childhood. Bisantrene should be evaluated with a five-day schedule in other pediatric malignancies. In children with acute leukemia previously treated with high dose aracytine, new combination regimen is warranted.

Busulfan disposition below the age of three: alteration in children with lysosomal storage disease.

Busulfan disposition is age-dependent with a higher clearance and a larger volume of distribution in children than in adults. The optimal dosage of busulfan needed to achieve bone marrow (BM) displacement in young children with malignant or nonmalignant disease remains to be defined. Using a gas chromatography-mass spectrometry assay, we evaluated plasma pharmacokinetics of busulfan in 33 children (median age, 9 months; range, 2 months to 2.75 years) with immune deficiencies, lysosomal storage diseases, acute leukemias, and malignant lymphohistiocytosis after an oral dose ranging from 0.9 to 2.6 mg/kg. The busulfan clearance (assuming a bioavailability of 1) ranged from 2.1 to 13.4 mL/min/kg with a mean of 6.8 mL/min/kg, which is higher than that reported in older children (4.5 mL/min/kg) and adults (2.9 mL/min/kg). Six children with lysosomal storage disease (5 with Hurler's disease, 1 with San Filippo's disease) had a prolonged elimination half-life (4.9 v 2.4 hours), a larger volume of distribution (3.4 v 1.2 L/kg) and a faster clearance (8.7 v 6.3 mL/min/kg) than the other 27 children. This suggests that a higher dose of busulfan will be required to achieve BM displacement in children with lysosomal storage disease. Over the dose range of 0.9 to 2.6 mg/kg, busulfan pharmacokinetics were linear. However, only 46% of the interpatient variation in systemic exposure could be ascribed to the dose. Given the wide interpatient variability in busulfan disposition, dose adjustment and drug monitoring will be needed to achieve the optimal dosage of busulfan in young children. The plasma busulfan levels required to achieve BM displacement need to be defined, especially in lysosomal storage diseases.

[Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM]. / Traitement des formes sévères de drépanocytose par allogreffe de moelle: expérience française (15 cas). SFGM.

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9), > 16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)