Analysis of telomeres in peripheral blood cells from patients with bone marrow failure.

Background: The determination of telomere length is useful for the characterization of dyskeratosis congenita (DC) and of aplastic anemias (AA) as well as hematological malignancies. Short telomeres result from a specific defect of telomere maintenance in DC and likely from higher cellular turnover in AA and hematological malignancies. Data are not conclusive for Diamond-Blackfan anemia (DBA), a pure erythroid aplasia due to defects of ribosomal proteins.

Accuracy of measuring mitral annular velocity by 2D speckle tracking imaging.

Background: Recent developments in 2D speckle tracking imaging allow not only measurements of regional myocardial strain, but also velocities of the mitral annulus. The aim of this study was to determine the accuracy of speckle tracking derived mitral annulus velocity compared with conventional pulsed wave Doppler measurements.

Methods: 2D speckle tracking was acquired from the apical 4-chamber view (QLab, Speckle SQ, Philips, Andover, MA) in 169 subjects.

Testicular function of survivors of childhood cancer: a comparative study between ifosfamide- and cyclophosphamide-based regimens.

Purpose: This study aimed at comparing gonadal toxicity of ifosfamide versus cyclophosphamide received during childhood.

Methods: The evaluation was based on basal FSH measurement. LH and testosterone were also measured in most of the patients.

Rituximab-based immunosuppression for autoimmune haemolytic anaemia in infants.

We report a case series of four infants with severe autoimmune haemolytic anaemia (AIHA) who responded to treatment with rituximab and cyclosporine after having failed first line therapy with high-dose steroid (prednisolone 4-8 mg/kg/d). Rituximab was started at 11-90 d from onset due to continued haemolysis; three infants also received cyclosporine A. Three of four infants reached complete response, defined as normal haemoglobin, reticulocytes and negative indices of haemolysis, at 7-21 months from diagnosis.

Etanercept as a salvage treatment for refractory aplastic anemia.

About 10-15% of patients with acquired aplastic anemia (AAA) have resistant/recurrent disease not eligible for standard treatment like hematopoietic stem cell transplantation and/or combined immunosuppression. We report a 17-year-old male with an 11 years history of AAA who, after two courses of immunosuppression, was red cell transfusion-dependent, severely thrombocytopenic, refractory to platelet transfusion, had iron overload and post-transfusion HCV infection. This patient achieved transfusion independence from platelets and normalized Hb after treatment with the anti-TNF agent Etanercept.

NOLA1 gene mutations in acquired aplastic anemia.

Background: Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita. TERC and TERT mutations were also found in patients with aplastic anemia. The aim of this work is to analyze the possible involvement of the telomerase complex gene NOLA1, in a population of Italian AA patients.

Treatment-related myelodysplastic syndrome after temozolomide use in a child: first report.

Temozolomide is an effective alkylating agent that is increasingly used for the treatment of pediatric brain tumors. Secondary, or treatment-related, myelodysplasia is a life-threatening complication of alkylating chemotherapy and has been reported in children with brain tumors after treatments other than temozolomide. We describe for the first time a case of temozolomide-related myelodysplasia in a child.

Synthesis of hydroxycinnamic acid glucuronides and investigation of their affinity for human serum albumin.

Hydroxycinnamic acids (HCAs) are among the most abundant dietary polyphenols. Recent bioavailability studies have shown that HCAs enter the blood circulation mainly as glucuronides, which are thus most likely to express their potential health effects. In this work, an efficient synthesis of HCA O-arylglucuronides is developed.

Bilateral adrenal neuroblastoma.

Background: Bilateral adrenal neuroblastoma is extremely rare. To date, 45 cases have been reported in the literature.

Procedures: We retrospectively identified and reviewed 15 cases of bilateral adrenal neuroblastoma, treated between 1988 and 2004, by the French Society of Pediatric Oncology.

[Childhood cerebral tumors: morbidity and follow-up into adulthood].

This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.

The murine cytomegalovirus cell death suppressor m38.5 binds Bax and blocks Bax-mediated mitochondrial outer membrane permeabilization.

Apoptosis is increasingly implicated as an early line of defense against viral infections. Viruses have devised numerous strategies to delay apoptosis of infected cells. Many viruses encode cell death suppressors that target mitochondrial apoptotic signaling pathway, indicating the importance of this pathway in the anti-viral response.

Fanconi anaemia: new strategies.

Fanconi anaemia (FA) is a rare genetic disease characterized by chromosomal instability, somatic abnormalities, marrow failure and cancer proness. The main cause of morbidity and mortality is bone marrow failure, which typically arises in the first decade of life and progresses to full-blown transfusion dependence and severe neutropenia in a variable number of years. Myelodysplastic syndrome (MDS) and AML may arise on the background of marrow failure, although cases of patients diagnosed with MDS or overt leukaemia before the full appearance of marrow aplasia are reported.

Long range spin ferromagnetic order with zero magnetization in (111)Sm(1-x)Gd(x)Al(2) films.

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Medulloblastoma: what is the role of molecular genetics?

Among pediatric malignancies, medulloblastoma (MB) is one of the most common malignant tumors of the CNS. In the past few years, thanks to a multidisciplinary approach including surgery, chemo- and radiation therapy, survival has significantly improved. Despite that, a third of patients still have a low chance of being cured and long-term survivors experience severe treatment-related sequelae.

Transforming growth factor-beta prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling.

Loss of mechanical loading induces rapid bone loss resulting from reduced osteoblastogenesis and decreased bone formation. The signaling mechanisms involved in this deleterious effect on skeletal metabolism remain poorly understood. We have previously shown that hindlimb suspension in rats increases osteoblast apoptosis associated with decreased phosphatidylinositol 3-kinase (PI3K) signaling.

FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival.

Fibroblast growth factor receptor (FGFR) signaling plays an important role in skeletogenesis. The molecular mechanisms triggered by activated FGFR in bone forming cells are however not fully understood. In this study, we identify a role for phosphatidylinositol 3-kinase (PI3K) signaling in cell apoptosis induced by FGFR2 activation in osteoblasts.

Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up.

Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin A (CyA) is the standard treatment for children with acquired aplastic anaemia (AAA) lacking a matched donor. Survival rates of more than 80% at 5 years are achieved, but the response is drug-dependent in 15-25% of cases. This study, of 42 consecutive children with AAA treated with IST, assessed the incidence of CyA-dependence, CyA and granulocyte colony-stimulating factor (G-CSF) tapering schedules and the impact of drug accumulation on progression to myelodysplasia/acute myeloid leukaemia (MDS/AML).

Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease.

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease.

[Good prognosis childhood cancers].

Wilms' tumours, neuroblastomas occurring in patients aged less than 1 year or localized neuroblastomas in older patients, malignant germ cells tumours, Hodgkin's disease, and malignant non Hodgkin lymphomas can be cured in more than 80% of the cases with treatment strategies adapted to risks factors in each tumour. The knowledge of low risk groups of patients allows the decrease of cumulative doses of alkylating agents and anthracyclines and limits the use of irradiation in order to reduce long term sequelae.

Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations.

Background And Objectives: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL). Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect.