Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002.

Purpose: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups.

Patients And Methods: For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations.

Towards reducing inequalities: European Standards of Care for Children with Cancer.

Despite the increase of cure rates in the treatment of children with cancer there is a significant discrepancy in the outcome within Europe. Data are showing us that there is a difference of 20% in outcomes for young people with cancer when comparing North and Western Europe with Central and Eastern Europe. One of the most important necessities, in order to be able to have comparable results and equitable outcomes about inequalities, is to have the Principle Treatment Centres, meeting a minimum level of standards and being accessible to continuously updated 'best practice'.

Ultrasound presentation of abdominal non-Hodgkin lymphomas in pediatric patients.

Introduction: Burkitt's lymphoma accounts for approximately 25% of lymphomas diagnosed in children of developmental age. The tumor is localized mainly in the intestine (usually in the ileocecal region), mesenteric lymph nodes and extraperitoneal space. The clinical symptoms are non-specific and include: abdominal pain, vomiting, gastrointestinal bleeding, and acute abdomen suggesting appendicitis or intestinal intussusception.

Asparagine synthetase (ASNS) gene polymorphism is associated with the outcome of childhood acute lymphoblastic leukemia by affecting early response to treatment.

The polymorphism of 14-bp tandem repeat sequence located in the ASNS gene probably acts as a transcriptional enhancer element and leads to higher expression of the gene in carriers of more than 2 repeats (>R2). We searched for an association with disease outcome in 264 children with ALL. A multivariate proportional hazard regression model adjusted for age at diagnosis (HR (95%CI)=1.

Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group.

Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004.

Measurement of back-bombardment temperature rise in microwave thermionic electron guns.

We describe a simple method to measure the back-bombardment heating temperature rise as a function of time in pulsed microwave thermionic guns using a fast rise-time InGaAs detector and optical pyrometer. Gaining knowledge of the nature of that temperature rise and the corresponding current out of the gun are the first steps in devising a scheme to counteract the back-bombardment heating which lengthens the micropulses, limits the macropulse length, and increases the energy spread of the emitted electron beam. We measured a temperature rise of 59 K in our LaB6 cathode which delivered a peak of 600 mA over a 5 μs RF pulse in our 0.

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children.

Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined.

Electron bunch energy and phase feed-forward stabilization system for the Mark V RF-linac free-electron laser.

An amplitude and phase compensation system has been developed and tested at the University of Hawai'i for the optimization of the RF drive system to the Mark V free-electron laser. Temporal uniformity of the RF drive is essential to the generation of an electron beam suitable for optimal free-electron laser performance and the operation of an inverse Compton scattering x-ray source. The design of the RF measurement and compensation system is described in detail and the results of RF phase compensation are presented.

Transfer of perfluorooctane sulfonic acid (PFOS) from contaminated feed to dairy milk.

Dietary intake is the predominant route for human exposure to perfluorooctane sulfonic acid (PFOS). Single pollution events may thus affect human exposure if polluted ground and water is used to produce animal feed or food. In this study, a physiologically based pharmacokinetic (PBPK-) model is derived that describes the uptake of PFOS from contaminated feed by cows and its subsequent elimination through the cows' milk.

Paediatric pseudoxanthoma elasticum with cardiovascular involvement.

Background: Pseudoxanthoma elasticum (PXE) is characterized by aberrant mineralization of connective tissues, causing considerable morbidity and mortality. The disease is typically of late onset, the skin manifestations first being noted in the teens or later. Another aberrant mineralization disorder, generalized arterial calcification of infancy (GACI), is present at birth and can demonstrate a phenotypic overlap with PXE.

The incidence and risk factors of stroke in patients with acute myocardial infarction treated invasively and concomitant impaired renal function.

Background: Impaired renal function is a marker of poor prognosis in patients with acute myocardial infarction (AMI). The aim of the study was to assess the incidence and independent predictors of stroke in population of patients with AMI treated invasively and concomitant impaired renal function (IRF).

Methods: We analyzed 2,520 consecutive AMI patients admitted to our Center between 2003 and 2007 and treated with percutaneous coronary intervention.

Development of treatment and clinical results in childhood acute myeloid leukemia in Poland.

Background: Since 1983 four consecutive unified regimens: acute myeloid leukemia-Polish pediatric leukemia/lymphoma study group (AML-PPLLSG) 83, AML-PPLLSG 94, AML-PPLLSG 98 and AML-BFM 2004 Interim, for AML have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). In this paper, we review four successive studies on the basis of acute myeloid leukemia-Berlin-Frankfurt-Munster (AML-BFM) protocol, in which a stepwise improvement of treatment outcome was observed. Treatment results of the last protocol AML-BFM 2004 Interim are presented in detail.

Absorption, distribution, and milk secretion of the perfluoroalkyl acids PFBS, PFHxS, PFOS, and PFOA by dairy cows fed naturally contaminated feed.

The transfer of the perfluoroalkyl acids (PFAAs) perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) from feed into tissue and milk of dairy cows was investigated. Holstein cows (n = 6) were fed a PFAA-contaminated feed for 28 days. After the PFAA-feeding period, three cows were slaughtered while the others were fed PFAA-free feed for another 21 days (depuration period).

New policies to address the global burden of childhood cancers.

Childhood cancer is a major global health issue. Every year, almost 100 000 children die from cancer before the age of 15 years, more than 90% of them in resource-limited countries. Here, we review the key policy issues for the delivery of better care, research, and education of professionals and patients.

ACTH resistance: genes and mechanisms.

ACTH resistance is a rare disorder typified by familial glucocorticoid deficiency (FGD), a genetically heterogeneous disease. Previously, genetic defects in FGD have been identified in the ACTH receptor gene (MC2R), its accessory protein (MRAP) and the steroidogenic acute regulatory protein gene (STAR). The defective mechanisms here are failures in ACTH ligand binding and/or receptor trafficking for MC2R and MRAP and, in the case of STAR mutations, inefficient cholesterol transport to allow steroidogenesis to proceed.

Familial glucocorticoid deficiency: New genes and mechanisms.

Familial Glucocorticoid deficiency (FGD), in which the adrenal cortex fails to produce glucocorticoids, was first shown to be caused by defects in the receptor for ACTH (MC2R) or its accessory protein (MRAP). Certain mutations in the steroidogenic acute regulatory protein (STAR) can also masquerade as FGD. Recently mutations in mini chromosome maintenance-deficient 4 homologue (MCM4) and nicotinamide nucleotide transhydrogenase (NNT), genes involved in DNA replication and antioxidant defence respectively, have been recognised in FGD cohorts.

[Extra-digestive reservoir of extended-spectrum beta-lactamase producing Enterobacteriaceae in non-infected patients: a study based on the systematic searching in urine and other clinical samples].

Our objective was to assess the extra-digestive reservoir of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE) by identifying them in clinical samples in which growing bacteria are not systematically analysed (bacterial identification and antimicrobial susceptibility testing) in routine practice. During a 5-week period, an analysis was systematically performed for Enterobacteriaceae colonies isolated in certain clinical samples (urine samples, respiratory-tract samples, and a group of samples called "miscellaneous samples") according to our study protocol. Samples in which an antimicrobial susceptibility testing was performed for bacteria isolated according to our routine practice were considered infected.

Individualized tumor response testing profile has a prognostic value in childhood acute leukemias: multicenter non-interventional long-term follow-up study.

A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine.

BCL11B, FLT3, NOTCH1 and FBXW7 mutation status in T-cell acute lymphoblastic leukemia patients.

T-cell acute lymphoblastic leukemia is a heterogeneous malignancy originating from developing lymphocyte precursors likely due to mutations in genes regulating thymocyte differentiation. Here, we characterized mutation status of BCL11B and FLT3 genes, presumably involved in T-ALL, together with FBXW7 and NOTCH1 as known players in T-ALL in 65 pediatric T-cell acute lymphoblastic leukemia patients. We also aimed at the assessment of prognostic value of NOTCH1 and FBXW7 mutations in ALL-IC BFM 2002 protocol.

The significance of heart rate turbulence in predicting major cardiovascular events in patients after myocardial infarction treated invasively.

Introduction: The role of heart rate turbulence (HRT) related to baroreflex sensitivity in predicting mortality after myocardial infarction (MI) has been confirmed by several investigators. However, the significance of HRT in predicting major adverse cardiovascular events (MACE) following acute MI is unknown.

Purpose: To analyze the prognostic value of HRT and other independent risk factors associated with autonomic regulation of MACE.

The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively.

Background: Diabetes (DM) deteriorates the prognosis in patients with coronary heart disease. However, the prognostic value of different glucose abnormalities (GA) other than DM in subjects with acute myocardial infarction (AMI) treated invasively remains unclear.

Aims: To assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention (PCI).

Effects of conjugated linoleic acids fed to dairy cows during early gestation on hematological, immunological, and metabolic characteristics of cows and their calves.

The aim of the present experiment was to test the stimulation ability of peripheral blood mononuclear cells (PBMC) expressed as stimulation index (SI) of newborn calves and of their dams fed a control fat supplement (CON, n=6) or 50 and 100g/d of a CLA-containing fat supplement (CLA50, n=5, and CLA100, n=6, respectively) during the preceding lactation period for 182 d after calving. The total intake of cis-9,trans-11 and trans-10,cis-12 CLA by groups CLA50 and CLA100 amounted to 4 and 8 g/d each, respectively. For this purpose, blood was collected immediately after parturition from calves before and after colostrum intake, and from cows after parturition and 21 d later.

Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency.

Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels.

Microvolt T-wave alternans and other noninvasive predictors of serious arrhythmic events in patients with an implanted cardioverter-defibrillator.

Background: Prediction of recurrent malignant ventricular tachyarrhythmias after insertion of a implantable cardioverter-defibrillator (ICD) is challenging. Microvolt T-wave alternans (MTWA) seems to be a promising marker of such events in ICD recipients.

Aim: To assess prognostic significance of MTWA and other noninvasive parameters in the prediction of major arrhythmic events after ICD implantation.

Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma.

According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES.