Schmiegelow K.,Copenhagen University |
Lausten Thomsen U.,Copenhagen University |
Pacheco C.E.,Hospital Infantil Manuel de Jesus Rivera |
Pieters R.,ErasmusMC Sophia Childrens Hospital |
And 7 more authors.
Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N=51) or more (N=3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83±0.05. Ages at diagnosis (Spearman correlation coefficient, r S=0.41, P=0.002) were significantly correlated, but not WBCs (r S=0.23, P=0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N=3), t(12;21) [ETV6/RUNX1] (N=1), MLL rearrangement (N=1) or t(1;19)(q23/p13) (N=1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N=5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N=6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P<0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors. © 2012 Macmillan Publishers Limited All rights reserved. Source
Brands M.M.M.G.,Erasmus Center for Lysosomal and Metabolic Diseases |
Oussoren E.,Erasmus Center for Lysosomal and Metabolic Diseases |
Ruijter G.J.G.,Erasmus Center for Lysosomal and Metabolic Diseases |
Vollebregt A.A.M.,Erasmus Center for Lysosomal and Metabolic Diseases |
And 5 more authors.
Molecular Genetics and Metabolism
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a rare progressive metabolic disorder characterized by coarse facial features, hepatosplenomegaly, restrictive pulmonary function, cardiac abnormalities and stiff joints. The disease is caused by a deficiency of the lysosomal enzyme N-acetyl galactosamine 4-sulfatase which leads to glycosaminoglycan (GAG) storage in various tissues. It presents as a clinical spectrum with varying disease progressions and severities. While the phases I/II/III studies proved the effectiveness of enzyme-replacement therapy (ERT) with recombinant human arylsulfatase B, long-term data are still scarce. Over treatment periods ranging from 1.3 to 5.4. years, this prospective open-label follow-up study in 11 Dutch mucopolysaccharidosis type VI patients (age 2-18. years) showed that ERT had significant positive effects on cardiac-wall diameters (IVSd and LVMI), left and right shoulder flexions (p < 0.001), liver size and spleen size (p < 0.001), urinary GAG excretion (p < 0.001), and the scales of quality of life (motor functioning and body functioning). ERT did not affect cardiac valve regurgitation or hearing function; HRQoL decreased slightly in two domains ('anxiety' and 'negative emotions'), and patients with the rapid and slow progressive forms of the disease differed with regard to baseline GAG excretion and GAG decrease during treatment. In conclusion, ERT had an effect on several clinical parameters. This effect was established in an open cohort of young mucopolysaccharidosis type VI patients. © 2013 Elsevier Inc. Source
Van Rijn S.F.,Travel Clinic Havenziekenhuis |
Driessen G.,ErasmusMC Sophia Childrens Hospital |
Overbosch D.,Travel Clinic Havenziekenhuis |
Overbosch D.,Institute of Tropical Medicine |
And 2 more authors.
Journal of Travel Medicine
Objective. Scarce data are available on the occurrence of ailments and diseases in children during travel. We studied the characteristics and frequencies of ailments in children aged 0 to 18 years and their parents during traveling. Methods. A prospective observational study on ailments reported by children and parents traveling to (sub)tropical countries was conducted. The ailments were semi-quantitatively graded as mild, moderate, or severe; ailments were expressed as ailment rates per personmonth of travel. Results. A total of 152 children and 47 parents kept track of their ailments for a total of 497 and 154 weeks, respectively. The children reported a mean ailment rate of 7.0 (5.6-8.4) ailments per personmonth of travel; 17.4% of the ailments were graded as moderate and 1.4% as severe. The parents reported a mean ailment rate of 4.4 (3.1-5.7); 10.8% of the ailments were graded as moderate and 5.5% as severe. Skin problems like insect bites, sunburn and itch, and abdominal complaints like diarrhea were frequently reported ailments in both children and parents. Children in the age category 12 to 18 years showed a significantly higher ailment rate of 11.2 (6.8-14.1) than their parents. Conclusions. Skin problems and abdominal problems like diarrhea are frequently reported ailments in children and their parents and show a high tendency to recur during travel. The majority of these ailments are mild but occasionally interfere with planned activities. Children in the age group 12 to 18 years are at a greater risk of developing ailments during a stay in a (sub)tropical country and they should be actively informed about the health risks of traveling to the tropics. © 2011 International Society of Travel Medicine. Source
Kuiper J.W.,mc Medical Center |
Vaschetto R.,mc Medical Center |
Vaschetto R.,University of Piemonte Orientale |
Corte F.D.,University of Piemonte Orientale |
And 2 more authors.
We review the current literature on the molecular mechanisms involved in the pathogenesis of acute kidney injury induced by plasma mediators released by mechanical ventilation. A comprehensive literature search in the PubMed database was performed and articles were identified that showed increased plasma levels of mediators where the increase was solely attributable to mechanical ventilation. A subsequent search revealed articles delineating the potential effects of each mediator on the kidney or kidney cells. Limited research has focused specifically on the relationship between mechanical ventilation and acute kidney injury. Only a limited number of plasma mediators has been implicated in mechanical ventilation-associated acute kidney injury. The number of mediators released during mechanical ventilation is far greater and includes pro- and anti-inflammatory mediators, but also mediators involved in coagulation, fibrinolysis, cell adhesion, apoptosis and cell growth. The potential effects of these mediators is pleiotropic and include effects on inflammation, cell recruitment, adhesion and infiltration, apoptosis and necrosis, vasoactivity, cell proliferation, coagulation and fibrinolysis, transporter regulation, lipid metabolism and cell signaling. Most research has focused on inflammatory and chemotactic mediators. There is a great disparity of knowledge of potential effects on the kidney between different mediators. From a theoretical point of view, the systemic release of several mediators induced by mechanical ventilation may play an important role in the pathophysiology of acute kidney injury. However, evidence supporting a causal relationship is lacking for the studied mediators. © 2011 BioMed Central Ltd. Source
Malogolowkin M.H.,Medical College of Wisconsin |
Spreafico F.,Pediatric Oncology Unit |
Dome J.S.,Childrens National Medical Center |
van Tinteren H.,Comprehensive Cancer Center |
And 5 more authors.
Pediatric Blood and Cancer
Background: Most relapses from Wilms' tumor occur within 2 years from diagnosis. This study aims to describe the incidence and outcome of patients who experienced a late recurrence (LR) more than 5 years after diagnosis across several clinical trials, and to develop evidence-based recommendations for follow-up surveillance. Methods: Available records on children with Wilms' tumor enrolled onto 10 national or international cooperative clinical trials were reviewed to identify patients who experienced a LR. Results: Seventy of 13,330 (0.5%) patients with Wilms' tumor experienced a LR. No gender bias was observed. Median time elapsing between initial Wilms' tumor diagnosis and first recurrence was 13.2 years (range: 5.1-17.3 years). Initial tumor stage was: stage I (15); stage II (19); stage III (14); stage IV (8); bilateral disease stage V (14). The most frequent sites of relapse were-abdomen: 21, lungs: 20, and contralateral kidney: 15. Thirty-five children died of disease progression. Recurrence in the contralateral kidney was associated with a better outcome (13/15 patients alive), while initial tumor stage did not seem to influence the post-recurrence outcome. Therapies administered at recurrence varied between centers, preventing any conclusion about the best salvage treatment. Conclusions: LR of Wilms' tumor is rare and associated with similar outcome to those experiencing earlier recurrence. The low rate of LR does not justify prolonged monitoring. Further study of the biology of these tumors may give us some insights in regards to mechanisms on tumor cell dormancy or cancer stem cell maintenance. Pediatr Blood Cancer 2013;60:1612-1615. © 2013 Wiley Periodicals, Inc. Source