Omvang en gevolgen van chronische aandoeningen bij kinderen

In a large study project we tried to determine the number of children and adolescents in the Netherlands with a chronic disease, and to evaluate the consequences of living with this. Therefore we defined and operationalised chronic diseases and health conditions in childhood, in a consensus procedure. Consensus was attained on a definition consisting of four criteria. A disease or condition is considered to be a chronic condition in childhood if (i) it occurs in children aged 0 up to 18 years, (2) the diagnosis is based on medical scientific knowledge and it can be diagnosed using reproducible and valid methods or instruments according to professional standards, (3) it is not (yet) curable, and (4) it has been present longer than three months or it will very probably last longer than three months, or it has occurred three times or more during the past year and will probably reoccur. Adding upon research findings and prevalence rates we estimated that at least 14% of children in the Netherlands are growing up with a chronic disease; counting for at least 500.000 children and adolescents. This is definitely an underestimation because for only a limited number of diseases reliable information was available. We also paid attention to studies on the social consequences of young adults who have been growing up with a chronic disease. Studies in the Netherlands in this area are limited as well. To evaluate the effects of pediatric and child health care on a societal level, and for the planning of health care facilities and other services for children and young adults with chronic conditions, valid and reliable prevalence estimates are needed

Osteoglycin prevents cardiac dilatation and dysfunction after myocardial infarction through infarct collagen strengthening

10.1161/CIRCRESAHA.116.304599Circulation Research1163425-436CIRU

Osteoglycin prevents cardiac dilatation and dysfunction after myocardial infarction through infarct collagen strengthening

Rationale: To maintain cardiac mechanical and structural integrity after an ischemic insult, profound alterations occur within the extracellular matrix. Osteoglycin is a small leucine-rich proteoglycan previously described as a marker of cardiac hypertrophy. Objective: To establish whether osteoglycin may play a role in cardiac integrity and function after myocardial infarction (MI). Methods and Results: Osteoglycin expression is associated with collagen deposition and scar formation in mouse and human MI. Absence of osteoglycin in mice resulted in significantly increased rupture-related mortality with tissue disruption, intramyocardial bleeding, and increased cardiac dysfunction, despite equal infarct sizes. Surviving osteoglycin null mice had greater infarct expansion in comparison with wild-type mice because of impaired collagen fibrillogenesis and maturation in the infarcts as revealed by electron microscopy and collagen polarization. Absence of osteoglycin did not affect cardiomyocyte hypertrophy in the remodeling remote myocardium. In cultured fibroblasts, osteoglycin knockdown or supplementation did not alter transforming growth factor-beta signaling. Adenoviral overexpression of osteoglycin in wild-type mice significantly improved collagen quality, thereby blunting cardiac dilatation and dysfunction after MI. In osteoglycin null mice, adenoviral overexpression of osteoglycin was unable to prevent rupture-related mortality because of insufficiently restoring osteoglycin protein levels in the heart. Finally, circulating osteoglycin levels in patients with heart failure were significantly increased in the patients with a previous history of MI compared with those with nonischemic heart failure and correlated with survival, left ventricular volumes, and other markers of fibrosis. Conclusions: Increased osteoglycin expression in the infarct scar promotes proper collagen maturation and protects against cardiac disruption and adverse remodeling after MI. In human heart failure, osteoglycin is a promising biomarker for ischemic heart failure

Vroeggeboorte, intra-uteriene groeiachterstand en lichamelijke ziehten op de volwassen leeftijd; resultaten van 19 jaar POPS-follow-up

Infants born very prematurely are at greater risk of neurosensory handicaps and developmental problems than are term born children. Premature birth, intrauterine growth retardation, and the combination of both, may also be risk factors for physical disease in adulthood. As this aspect has been little studied so far, we looked into its first signs in the pops-cohort (Project On Preterm and Small for gestational age infants). Prematurity seems to be a risk factor for the development of insulin resistance. The risk is extra high for individuals showing disposition to obesity at later age. Having experienced intrauterine growth retardation even increases the risk. Former premature infants on average show higher mean systolic blood pressure, yet unrelated to degree of intrauterine growth retardation. Renal function (clearance and protein excretion) in young adulthood is less favorable for prematurely born individuals who also experienced intrauterine growth retardation. Prematurely born children show more airway symptoms and poorer lung function in young adulthood. We conclude that neonatal follow up is not only indicated for very premature infants but also for children who experienced severe intrauterine or neonatal growth retardation. Pediatricians ought to inform parents and children as well as the family doctor that prematurity or intrauterine growth retardation may be risk factors for chronic disease at adult age. Active prevention of obesity from an early age onwards is indicated for prematurely born children who experienced intrauterine growth retardation. Family doctors should be extra alert to the development of particularly hypertension and microalbuminuria when these children reach young adult age; a regular check-up for example every two years is recommended. Awareness of their medical history may stimulate the children themselves to prevent obesity, take up sports, and never start smoking

Relevance of nitric oxide for myocardial remodeling.

Endogenous myocardial nitric oxide (NO) may modulate the transition from adaptive to maladaptive remodeling leading to heart failure. In rodent models of pressure overload or myocardial infarction, the three NO synthase (NOS) isoforms were shown to play a neutral, protective, or even adverse role in myocardial remodeling, depending on the quantity of NO produced, the location of each NOS and their regulators, the prevailing oxidant stress and resultant NO/oxidant balance, as well as NOS coupling/dimerization. Beside neuronal NOS and--in specific conditions--inducible NOS isoforms, endothelial NOS (eNOS) exerts cardioprotective effects on pressure-overload, ischemia/reperfusion, and myocardial infarction-induced myocardial remodeling, provided the enzyme remains in a coupled state. Besides its effects on excitation-contraction coupling in response to stretch, eNOS acts as an "endogenous beta-blocker" by restoring the sympathovagal balance, opposing excessive hypertrophy as well as promoting vasodilatation and neoangiogenesis, thereby contributing to tissue repair. As eNOS was also shown to mediate the beneficial effects of cardiovascular drugs commonly used in patients with heart failure, strategies to increase its expression and/or coupled catalytic activity in the myocardium offer new therapeutic avenues for the treatment of this disease