La survenue d’une acidose lactique dans l’asthme aigu grave (AAG) est classique chez l’adulte mais peu décrite chez l’enfant. Sa reconnaissance peut avoir des conséquences sur la prise en charge ...thérapeutique de la crise d’asthme. Une petite fille de 2 ans a été hospitalisée en réanimation pédiatrique pour un AAG, traité par oxygénothérapie à haut débit, méthylprednisolone et salbutamol par voie intraveineuse. Elle a présenté une acidose métabolique (pH=7,29) avec hypocapnie (26 mmHg), chute des bicarbonates (12 mmol/L), trou anionique (20 mmol/L) et augmentation des lactates (8 mmol/L). La recherche d’une maladie métabolique sous-jacente a été négative. L’évolution a été favorable avec amélioration spontanée de l’acidose lactique permettant la sortie de l’unité de réanimation après 72 heures. L’origine d’une acidose lactique au cours de l’AAG est multifactorielle. Bien que sa résolution soit spontanée, il est essentiel de la reconnaître car elle peut modifier la symptomatologie respiratoire et conduire à une escalade thérapeutique inappropriée.
Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The image resolution produced by a lens/camera system is limited by the digital sampling frequency of the sensor and the diffraction limit as imposed by the front aperture diameter of the optics. A ...previous study using Image Phase Alignment Super-Sampling (ImPASS) demonstrated that Fourier phase information from a sequence of slightly displaced images can be used to achieve image resolution beyond the digital sampling frequency. In continuation of that work, this study applies ImPASS to sequences of slightly displaced empirical images for a range of aperture settings. The frames are up-sampled, aligned, and combined into a single frame. Application of Self-Deconvolving Data Restoration Algorithm (SeDDaRA) deconvolution reveals features with higher resolution. The slanted edge technique is applied to the processed images to establish the angular resolution of the system as a function of the effective f-number. When compared to Abbe’s resolution criteria, the measurements reveal that this super-sampling method produces image resolution that subceeds the diffraction limit of the lens/camera system.
Background
Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose‐dependent cardiotoxicity. In an ...effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.
Objectives
The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010) and EMBASE (1980 to November 2010) databases. In addition, we handsearched reference lists, conference proceedings of the International Society of Paediatric Oncology (SIOP) and American Society of Clinical Oncology (ASCO) meetings (1998 to 2010) and ongoing trials registers.
Selection criteria
Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional therapy or placebo in cancer patients (children and adults) receiving anthracyclines.
Data collection and analysis
Two review authors independently performed the study selection, risk of bias assessment and data extraction including adverse effects.
Main results
We identified RCTs for the eight cardioprotective agents N‐acetylcysteine, phenethylamines, coenzyme Q10, a combination of vitamins E and C and N‐acetylcysteine, L‐carnitine, carvedilol, amifostine and dexrazoxane (mostly for adults with advanced breast cancer). All studies had methodological limitations and for the first seven agents there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The 10 included studies on dexrazoxane enrolled 1619 patients. The meta‐analysis for dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (risk ratio (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control groups. The results for adverse effects were ambiguous. No significant difference in the occurrence of secondary malignancies was identified.
Authors' conclusions
No definitive conclusions can be made about the efficacy of cardioprotective agents for which pooling of results was impossible. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control groups was identified. The evidence available did not allow us to reach any definite conclusions about adverse effects. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects for each individual patient.
Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from ...serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms.
To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH) arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases), SHH signaling (B; 15 cases), expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively) or photoreceptor genes (D and E; both 11 cases). Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E. Patients below 3 yrs of age had type B, D, or E tumors. Type B included most desmoplastic cases. We validated and confirmed the molecular subtypes and their associated clinicopathological features with expression data from a second independent series of 46 medulloblastomas.
The new medulloblastoma classification presented in this study will greatly enhance the understanding of this heterogeneous disease. It will enable a better selection and evaluation of patients in clinical trials, and it will support the development of new molecular targeted therapies. Ultimately, our results may lead to more individualized therapies with improved cure rates and a better quality of life.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transcriptional regulation in eukaryotes occurs within a chromatin setting, and is strongly influenced by the post-translational modification of histones, the building blocks of chromatin, such as ...methylation, phosphorylation and acetylation. Acetylation is probably the best understood of these modifications: hyperacetylation leads to an increase in the expression of particular genes, and hypoacetylation has the opposite effect. Many studies have identified several large, multisubunit enzyme complexes that are responsible for the targeted deacetylation of histones. The aim of this review is to give a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity. SAGE (serial analysis of gene expression) data show that HDACs are generally expressed in almost all tissues investigated. Surprisingly, no major differences were observed between the expression pattern in normal and malignant tissues. However, significant variation in HDAC expression was observed within tissue types. HDAC inhibitors have been shown to induce specific changes in gene expression and to influence a variety of other processes, including growth arrest, differentiation, cytotoxicity and induction of apoptosis. This challenging field has generated many fascinating results which will ultimately lead to a better understanding of the mechanism of gene transcription as a whole.
To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs).
We determined CEs grade 3 or higher: congestive heart ...failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events CTCAE, version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models.
Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI, 3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%) compared with other treatments. In the proportional hazards analyses, anthracycline (dose), cardiac irradiation (dose), combination of these treatments, and congenital heart disease were significantly associated with developing a CE. We demonstrated an exponential relationship between the cumulative anthracycline dose, cardiac irradiation dose, and risk of CE.
CCSs have a high risk of developing symptomatic CEs at an early age. The most common CE was CHF. Survivors treated with both anthracyclines and radiotherapy have the highest risk; after 30 years, one in eight will develop severe heart disease. The use of potentially cardiotoxic treatments should be reconsidered for high-risk groups, and frequent follow-up for high-risk survivors is needed.
•Laser surface melting treatments require neither additional feedstock nor contact.•By affecting 1μm, the pitting potential of laser treated 304L increases by 500mV.•Surface modification of laser ...treated sample observed by TEM.•The physico-chemical properties of the surface are correlated to overlap rate.•AISI 304L pitting corrosion resistance strongly depends of overlap rate.
Changes induced in the surface properties of AISI 304L stainless steel when it is treated with a nanopulsed ytterbium-doped fiber laser were investigated to determine the microscale distribution of its physico-chemical properties. A Gaussian energy distribution was created with a radius of 71μm (1/e2) at the focal point. Local investigations were carried out using transmission electron microscopy to consider the effect of overlapping individual laser impacts. The results obtained reveal that laser surface melting leads to changes in the crystallographic structure of the steel through the formation of a δ-ferritic phase. It also results in the creation of an oxide layer that increases the corrosion resistance of the steel, with the chemical composition, structure and thickness of this layer being dependent on the overlap percentage and the position along the beam radius. Measurement of the localized corrosion resistance in a 30gL−1 NaCl solution using polarization curves found that optimal laser treatment conditions can led to an increase in the breakdown potential of more than 500mV, which corresponds to a significant improvement in corrosion resistance.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity and mortality. Our aim was to identify genetic variants ...associated with ACT in patients treated for childhood cancer.
We carried out a study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia, with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands.
We identified a highly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 × 10(-5) for all cohorts combined). Additional associations (P < .01) with risk and protective variants in other genes including SLC28A1 and several adenosine triphosphate-binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further explored combining multiple variants into a single-prediction model together with clinical risk factors and classification of patients into three risk groups. In the high-risk group, 75% of patients were accurately predicted to develop ACT, with 36% developing this within the first year alone, whereas in the low-risk group, 96% of patients were accurately predicted not to develop ACT.
We have identified multiple genetic variants in SLC28A3 and other genes associated with ACT. Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.
PDF
