[Pediatric medulloblastoma: Retrospective series of 52 patients]. / Médulloblastomes de l'enfant: étude rétrospective portant sur 52 patients.

PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

Spontaneous bacterial peritonitis by Pasteurella multocida under treatment with rifaximin.

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Recently, rifaximin, a non-absorbable antibiotic which is used to prevent recurrent hepatic encephalopathy, has been proposed as effective prophylaxis for SBP. Here, we present an unusual case of SBP under treatment with rifaximin. A 50-year-old woman with liver cirrhosis was admitted because of tense ascites and abdominal pain. She was under long-term oral prophylaxis with rifaximin due to hepatic encephalopathy. Paracentesis revealed SBP caused by Pasteurella multocida, which was sensitive to multiple antibiotics, including rifaximin. Treatment with ceftriaxone resulted in rapid resolution of the peritonitis and restoration of the patient. Since P. multocida is usually transmitted from pets, the patient's cat was tested and could be identified as the most likely source of infection. This case should elicit our awareness that uncommon pathogens and unusual routes of transmission may lead to SBP, despite antibacterial prophylaxis with non-absorbable antibiotics. Nevertheless, such infections may still remain sensitive to systemic therapy with conventional antibiotics.

Cyclic GMP-dependent protein kinase potentiates serotonin-induced Egr-1 binding activity in PC12 cells.

The NO/cyclic GMP (cGMP) signal transduction pathway, which involves the cGMP-dependent protein kinase (PKG), regulates transcription of several genes, including immediate early genes. Using transfection experiments with the PKG-Ialpha cDNA cloned from human aorta, we show here that addition of membrane-permeable cGMP analogues to PC12 cells slightly upregulated ERK MAP (mitogen-activated protein) kinase. Likewise, PKG-Ialpha was found to activate weakly DNA binding activity of the Egr-1 transcription factor. On the other hand, PKG-Ialpha overexpression was shown to tremendously amplify the Egr-1 binding activity induced by the neurotransmitter serotonin, which activates egr-1 gene expression also via the stimulation of the ERK MAP kinase pathway. Since this potentiation occurred neither at the level of ERK nor at the egr-1 transcriptional level, the mechanism of amplification probably results from the convergence of ERK and PKG pathways at the level of the transcription factor Egr-1.

The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia.

This study was undertaken to show that a high survival rate can be obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden (stage, resection status, percentage of blasts in bone marrow, and central nervous system [CNS] involvement) and early response to chemotherapy, to investigate actual prognostic factors, and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma. Patients were classified into 3 risk groups. Group A (resected stage I and abdominal stage II) received 2 courses of vincristine, cyclophosphamide, doxorubicin, and prednisone. Group B (patients not eligible for groups A or C) received 5 courses of chemotherapy with, in addition, high-dose methotrexate, 3 g/m(2) over 3 hours; infusional cytarabine; and intrathecal (IT) methotrexate. Group C (patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m(2); high-dose cytarabine; etoposide; and triple IT. Except in group A, treatment started with a prephase (COP, low-dose vincristine and cyclophosphamide). It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)

PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells.

The t(15;17) translocation, found in 95% of acute promyelocytic leukemia, encodes a promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) fusion protein. Complete remission of acute promyelocytic leukemia can be obtained by treating patients with all-trans retinoic acid, and PML-RARalpha plays a major role in mediating retinoic acid effects in leukemia cells. A main model proposed for acute promyelocytic leukemia is that PML-RARalpha exerts its oncogenic effects by repressing the expression of retinoic acid-inducible genes critical to myeloid differentiation. By applying subtraction cloning to acute promyelocytic leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARalpha target gene encoding an Adaptor Molecule-1), which encodes a novel adaptor protein sharing structural homologies with the SLAP-130/fyb adaptor. PRAM-1 is expressed and regulated during normal human myelopoiesis. In U937 myeloid precursor cells, PRAM-1 expression is inhibited by expression of PML-RARalpha in the absence of ligand and de novo superinduced by retinoic acid. PRAM-1 associates with other adaptors, SLP-76 and SKAP-55HOM, in myeloid cell lines and with protein tyrosine kinase lyn. By providing the first evidence that PML-RARalpha dysregulates expression of an adaptor protein, our data open new insights into signaling events that are disrupted during transformation by PML-RARalpha and induced by retinoic acid during de novo differentiation of acute promyelocytic leukemia cells.

Complete suppression of protein synthesis during anoxia with no post-anoxia protein synthesis debt in the red-eared slider turtle Trachemys scripta elegans.

Two previous studies of the effects of anoxia on protein synthesis in anoxia-tolerant turtles (Trachemys scripta elegans, Chrysemys picta bellii) have generated opposing results. Using the flooding-dose method, we measured the rate of protein synthesis following injection and incorporation of a large dose of radiolabelled phenylalanine to resolve the question of whether anoxia results in a downregulation of protein synthesis. After 1 h of anoxia, levels of protein-incorporated radiolabel indicated that protein synthesis rates in the intestine, heart, liver, brain, muscle and lungs were not significantly different from those of normoxic controls. However, from 1 to 6 h of anoxia, quantities of protein-incorporated radiolabel did not increase, suggesting that protein synthesis had ceased or had decreased below a measurable level. There was also no significant post-anoxia increase in protein synthesis rates above normoxic control levels during 3 h of recovery from anoxia. RNA-to-protein ratios did not change significantly in any tissue except the heart, in which RNA levels decreased below normoxic control levels after 6 h of anoxia. Except in the heart, downregulation of protein synthesis during anoxia does not appear to be mediated by changes in tissue RNA concentration.

N-actylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress.

In vitro administration of lead acetate (PbA) to cultures of Chinese hamster ovary (CHO) cells had a concentration-dependent inhibitory effect on colony formation. Colony formation was returned to control levels in lead-treated cultures that were supplemented with 1 mM N-actylcysteine (NAC), a well-documented synthetic antioxidant. In order to investigate the nature of NAC's protective effect, we measured L-gamma-glutamyl-L-cysteinylglycine (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and catalase activity both in the presence and absence of NAC in lead-exposed CHO cells. Increases in both MDA levels (p < 0.05) and catalase activity (P < 0.05) were observed in cultures that received only PbA, but supplementation with NAC returned these measures to pretreatment levels. The ratio of GSH to GSSG increased in lead-exposed cells incubated in NAC-enhanced media, but declined in cultures treated with PbA only. Our results suggest that NAC can confer protection against lead-induced oxidative stress to CHO cells, possibly through the enhancement of the cell's own antioxidant defense mechanisms.

Physiologic and clinicopathologic effects of crude oil on loggerhead sea turtles.

The physiologic and clinicopathologic effects of weathered South Louisiana crude oil exposure were studied in the laboratory in juvenile loggerhead sea turtles. Sea turtles ingested oil incidentally, and oil was observed clinging to the nares, eyes, and upper esophagus, and was found in the feces. Oiled turtles had up to a four-fold increase in white blood cell counts, a 50% reduction in red blood cell counts, and red blood cell polychromasia. Most serum blood chemistries (e.g., BUN, protein) were within normal ranges, although glucose returned more slowly to baseline values than in the controls. Gross and histologic changes were present in the skin and mucosal surfaces of oiled turtles, including acute inflammatory cell infiltrates, dysplasia of epidermal epithelium, and a loss of cellular architectural organization of hte skin layers. The cellular changes in the epidermis are of particular concern because they may increase susceptibility to infection. Although many of the observed physiological insults resolved with a 21-day recovery period, the long-term biological effects of oil on sea turtles remain completely unknown.

Successful blood stem cell collection and transplant in children weighing less than 25 kg.

Peripheral blood stem cells (PBSCs) were collected for autotransplantation in 20 children (median age 4 years, range 0.5-10 years) weighing < 25 kg (median 14.5 kg, range 6.8-24 kg) with various malignant diseases: leukemias and lymphomas (n = 6), solid tumours (n = 14). Cytaphereses were carried out after standard chemotherapy (n = 10), mobilizing high-dose chemotherapy (n = 9) or radiotherapy alone (n = 1). In 13 children PBSCs were harvested after haematopoietic growth factor (HGF) administration. PBSCs were collected using a continuous flow blood separator (Cobe Spectra). In 13 patients access was through a central catheter with peripheral venous return, in 4 patients access was through a central catheter with return through a femoral catheter; one patient had femoral catheter access with peripheral venous return and two patients had both access and return through peripheral veins. For 19 patients the extracorporeal line was primed with red blood cells. The median blood flow rate was 13.8 ml/min (range 7-22 ml/min). Sixty-six procedures (mean 3.3/patient, range 1-4) were performed with a mean total collection time of 8.5 h. The median number of granulocyte-macrophage colony-forming units (CFU-GM) collected was 37.7 x 10(4)/kg (mean 107 x 10(4)/kg, range 1.05-882 x 10(4)/kg). The number of CFU-GM collected per procedure in children with HGF was 7.8-fold higher than in children without HGF (median 20.4 versus 2.6 x 10(4) CFU-GM/kg body weight, respectively). There were no consistent effects on peripheral blood counts except on platelet counts which decreased following each procedure (median decrease in platelet count was 36%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary severe neonatal hyperparathyroidism. Significance of genetic study and emergency parathyroidectomy]. / Hyperparathyroïdie primitive sévère à début néonatal. Intérêt de l'étude génétique et de la parathyroïdectomie d'urgence.

Primary hyperparathyroidism in the newborn is uncommon. The clinical features as well as histological lesions of the parathyroid glands are quite different from those in the adult. The degree of hypercalcemia and the high frequency of pulmonary complications may threaten the life of the infant. Management is straight forward: early surgical removal and supplementation with calcium and vitamins should be quickly followed by an autograft. In the severe case herein reported, the diagnosis, suggested by family history, was confirmed by a rapid increase in calcemia as well as by very characteristic skeletal lesions.

Neonatal primary hyperparathyroidism: total parathyroidectomy with autotransplantation of cryopreserved parathyroid tissue.

Primary neonatal hyperparathyroidism is a life threatening disease because of severe hypercalcemia. The best therapy is early total parathyroidectomy which requires permanent replacement therapy. We describe the first case treated by total parathyroidectomy and late autotransplantation of cryopreserved parathyroid tissue. Twenty months after transplantation, serum calcium and phosphate levels are normal in the absence of any supplementary treatment.

Cross-reactive idiotypes and common antigen binding specificities expressed by a series of murine B-cell lymphomas: etiological implications.

A series of 27 B-cell lymphomas (designated the CH series), induced in B10.H-2aH-4b p/Wts mice by intense adoptive immunization with sheep erythrocytes, was found to represent a subset of the total B-cell repertoire. This subset was characterized by expression of a limited number of Ig heavy chain variable regions, as evidenced by the presence of cross-reactive idiotypes and common antigen binding specificities. Twenty-one of the 27 CH lymphomas studied were classified into five groups, defined by a particular cross-reactive idiotype; four of these groups were linked in a single network. Seven of 16 idiotypes defined by absorption analysis were present on lymphomas bearing either kappa or lambda light chains and so were localized to the heavy chain variable region. The surface Ig on 14 CH lymphomas was found to be specific for epitopes on certain erythrocytes (bromelain-treated autologous erythrocytes, sheep, and chicken erythrocytes) or E. coli. We propose that the CH lymphomas represent the malignant counterparts of a subset of idiotypically related, normal B cells in B10.H-2aH-4b p/Wts mice. Perturbation of this idiotype network, by hyperimmunization with an antigen for which some of the members are specific (sheep erythrocytes), increases the risk for neoplasia. Possible mechanisms for this are discussed.