Endothelial cells were isolated from arteries and veins obtained from elderly people at autopsy and propagated for 37 to 69 population doublings. The cells secreted tissue-type plasminogen activator (t-PA) and PA inhibitor-1, and, after subculturing, urokinase-type PA (u-PA) antigen. The following differences between endothelial cells from adult arteries and veins were observed: 1) The cells had the potential to be propagated as a healthy monolayer. The diameter of aortic endothelial cells increased after 8 to 19 population doublings, while a homogeneous population of small diameter vena cava cells was retained for 35 population doublings. 2) The amount of secreted t-PA varied. Vena cava cells produced four times more t-PA than aorta cells, and 20-fold more than umbilical artery or vein endothelial cells. The t-PA mRNA content of vena cava cells did not exceed that of aorta cells, but was fourfold greater than that of umbilical cord endothelial cells. 3) The release of u-PA antigen varied. No u-PA antigen was detectable in conditioned medium of primary cultures of human aorta and vena cava endothelial cells or of early passage vena cava cells. After prolonged subculturing, vena cava cells started to secrete u-PA. Endothelial cells from aorta and other adult arteries, however, started secreting u-PA after one to four passages, parallel to the occurrence of enlarged endothelial cells. u-PA was present as a u-PA/inhibitor complex and as a single-chain u-PA. These differences may be developmentally related to their artery or vein origin or may reflect differences acquired during the "life history" of these blood vessels in vivo. Our data suggest that the release of u-PA antigen by human macrovascular endothelial cells can be used as an indicator of cell senescence.
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BACKGROUND: Patients who underwent surgery for aortic coarctation (COA) have an increased risk of arterial hypertension. We aimed at evaluating (1) differences between hypertensive and non-hypertensive patients and (2) the value of cardiopulmonary exercise testing (CPET) to predict the development or progression of hypertension. METHODS: Between 1999 and 2010, CPET was performed in 223 COA-patients of whom 122 had resting blood pressures of <140/90 mmHg without medication, and 101 were considered hypertensive. Comparative statistics were performed. Cox regression analysis was used to assess the relation between demographic, clinical and exercise variables and the development/progression of hypertension. RESULTS: At baseline, hypertensive patients were older (p=0.007), were more often male (p=0.004) and had repair at later age (p=0.008) when compared to normotensive patients. After 3.6 ± 1.2 years, 29/120 (25%) normotensive patients developed hypertension. In normotensives, VE/VCO2-slope (p=0.0016) and peak systolic blood pressure (SBP; p=0.049) were significantly related to the development of hypertension during follow-up. Cut-off points related to higher risk for hypertension, based on best sensitivity and specificity, were defined as VE/VCO2-slope ≥ 27 and peak SBP ≥ 220 mmHg. In the hypertensive group, antihypertensive medication was started/extended in 48/101 (48%) patients. Only age was associated with the need to start/extend antihypertensive therapy in this group (p=0.042). CONCLUSIONS: Higher VE/VCO2-slope and higher peak SBP are risk factors for the development of hypertension in adults with COA. Cardiopulmonary exercise testing may guide clinical decision making regarding close blood pressure control and preventive lifestyle recommendations.
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Klotho knock-out mice are an important model for vascular calcification, which is associated with chronic kidney disease. In chronic kidney disease, serum magnesium inversely correlates with vascular calcification. Here we determine the effects of serum magnesium on aortic calcification in Klotho knock-out mice treated with a minimal or a high magnesium diet from birth. After eight weeks, serum biochemistry and aorta and bone tissues were studied. Protective effects of magnesium were characterized by RNA-sequencing of the aorta and micro-CT analysis was performed to study bone integrity. A high magnesium diet prevented vascular calcification and aortic gene expression of Runx2 and matrix Gla protein found in such mice on the minimal magnesium diet. Differential expression of inflammation and extracellular matrix remodeling genes accompanied the beneficial effects of magnesium on calcification. High dietary magnesium did not affect serum parathyroid hormone, 1,25-dihydroxyvitamin D3 or calcium. High magnesium intake prevented vascular calcification despite increased fibroblast growth factor-23 and phosphate concentration in the knock-out mice. Compared to mice on the minimal magnesium diet, the high magnesium diet reduced femoral bone mineral density by 20% and caused excessive osteoid formation indicating osteomalacia. Osteoclast activity was unaffected by the high magnesium diet. In Saos-2 osteoblasts, magnesium supplementation reduced mineralization independent of osteoblast function. Thus, high dietary magnesium prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways within the aorta. Hence magnesium treatment may be promising to prevent vascular calcification, but the risk for osteomalacia should be considered.
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Voor patiënten die radiologische verrichtingen ondergaan bestaan geen dosislimieten, maar wel zogenaamde Diagnostische ReferentieNiveaus (DRN’s). Dit zijn richtwaarden voor de hoeveelheid straling voor de gemiddelde patiënt bij goede praktijkvoering. In Nederland bestaan nationale DRN’s voor slechts 11 radiologische verrichtingen. In andere Europese landen zijn dat er vaak beduidend meer. Zo ontbreken in Nederland DRN’s voor interventie-radiologische verrichtingen (interventies), terwijl dit juist verrichtingen zijn waarbij vaak relatief hoge stralingsdoses worden uitgedeeld. In deze studie, die gebaseerd is op het afstudeerwerk van twee van de auteurs (GH en MtS), is als proof-of-principle een lokaal DRN afgeleid uit data van een enkel ziekenhuis (het Dijklander ziekenhuis). Voor dit lokale DRN is data verzameld van percutane transluminale angioplastiek (PTA) in de arteria femoralis superficialis (AFS), uitgevoerd met dezelfde apparatuur in één angiografiekamer door twee radiologen. In totaal zijn daarbij 52 complicatievrije interventies geïncludeerd. Uit de verzamelde data is als 75 percentielwaarde een lokaal DRN voor PTA van de AFS afgeleid van 50,9 Gy*cm2. Dit is ruim 20 Gy*cm2 lager dan gevonden in twee andere Europese studies. In die studies werd daarentegen wel veel meer data geïncludeerd van verschillende radiologie-afdelingen. Deze studie laat zien dat het ook in Nederland mogelijk is om voor een interventie een DRN op te stellen. Het verdient de aanbeveling deze studie te herhalen of uit te breiden met data van diverse andere Nederlandse ziekenhuizen om zodoende een nationaal DRN te bepalenn
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Draagt rewilding bij aan biodiversiteitsherstel? Om die vraag te beantwoorden monitoren vmbo-leerlingen en mbo- en hbo-studenten planten en insecten op een afgebakend stukje schoolterrein waar beheer wordt losgelaten. Over het Rewilding project van Lectoraat Ecologisch Wijs van Aeres Hogeschool, met Jetske de Boer en Marlies Beukenkamp.
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BACKGROUND: Intra-abdominal hypertension is frequently present in critically ill patients and is an independent predictor for mortality. Risk factors for intra-abdominal hypertension and abdominal compartment syndrome have been widely investigated. However, data are lacking on prevalence and outcome in high-risk patients. Our objectives in this study were to investigate prevalence and outcome of intra-abdominal hypertension and abdominal compartment syndrome in high-risk patients in a prospective, observational, single-center cohort study.RESULTS: Between March 2014 and March 2016, we included 503 patients, 307 males (61%) and 196 females (39%). Patients admitted to the intensive care unit with a diagnosis of pancreatitis, elective or emergency open abdominal aorta surgery, orthotopic liver transplantation, other elective or emergency major abdominal surgery and trauma were enrolled. One hundred and sixty four (33%) patients developed intra-abdominal hypertension and 18 (3.6%) patients developed abdominal compartment syndrome. Highest prevalence of abdominal compartment syndrome occurred in pancreatitis (57%) followed by orthotopic liver transplantation (7%) and abdominal aorta surgery (5%). Length of intensive care stay increased by a factor 4 in patients with intra-abdominal hypertension and a factor 9 in abdominal compartment syndrome, compared to patients with normal intra-abdominal pressure. Rate of renal replacement therapy was higher in abdominal compartment syndrome (38.9%) and intra-abdominal hypertension (8.2%) compared to patients with normal intra-abdominal pressure (1.2%). Both intensive care mortality and 90-day mortality were significantly higher in intra-abdominal hypertension (4.8% and 15.2%) and abdominal compartment syndrome (16.7% and 38.9%) compared to normal intra-abdominal pressure (1.2% and 7.1%). Body mass index (odds ratio 1.08, 95% confidence interval 1.03-1.13), mechanical ventilation at admission (OR 3.52, 95% CI 2.08-5.96) and Apache IV score (OR 1.03, 95% CI 1.02-1.04) were independent risk factors for the development of intra-abdominal hypertension or abdominal compartment syndrome.CONCLUSIONS: The prevalence of abdominal compartment syndrome was 3.6% and the prevalence of intra-abdominal hypertension was 33% in this cohort of high-risk patients. Morbidity and mortality increased when intra-abdominal hypertension or abdominal compartment syndrome was present. The patient most at risk of IAH or ACS in this high-risk cohort has a BMI > 30 kg/m2 and was admitted to the ICU after emergency abdominal surgery or with a diagnosis of pancreatitis.
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In de kolommen van dit blad konden we onlangs optekenen dat gebiedsontwikkeling inmiddels aan versie 3.0 toe is. Projectmanagement,dat als vak al veel langer bestaat, maar na voorbereidende opleidingen als Bouwkunde nog geen herkenbare structuur heeft, kan daarbij niet achterblijven. Tenminste, als we een recente publicatie van de Hogeschool Utrecht en Pro6Managers mogen geloven die onder die titel is verschenen. Maar is er inderdaad sprake van een vak dat zich onder druk van de nieuwe realiteit opnieuw moet uitvinden? Of is er veeleer sprake van een evolutie? En wat is de rol van het onderwijs in dit verband? Allemaal vragen die tijdens een rondetafelgesprek op diezelfde Hogeschool aan de orde kwamen. Een verslag in drie blokken.
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A growing number of older patients undergo cardiac surgery. Some of these patients are at increased risk of post-operative functional decline, potentially leading to reduced quality of life and autonomy, and other negative health outcomes. First step in prevention is to identify patients at risk of functional decline. There are no current published tools available to predict functional decline following cardiac surgery. The objective was to validate the identification of seniors at risk—hospitalised patients (ISAR-HP), in older patients undergoing cardiac surgery. A multicenter cohort study was performed in cardiac surgery wards of two university hospitals with follow-up 3 months after hospital admission. Inclusion criteria: consecutive cardiac surgery patients, aged ≥65. Functional decline was defined as a decline of at least one point on the Katz ADL Index at follow-up compared with preadmission status.
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In deze rapportage worden de resultaten weergegeven uit het kwantitatieve onderzoek dat in 2012 en 2013 is uitgevoerd bij de Utrechtse Open Monumentendag. Hiertoe worden eerst de demografische en festigrafische variabelen behandeld, vervolgens de gebruikte media, daarna de tevredenheid en ten slotte de locaties waar men is geweest. In de tabellen is het aantal respondenten aangegeven dat antwoord heeft gegeven, daarachter staat tussen haakjes het percentage. Bij een aantal variabelen zijn de gemiddelden weergegeven. Deze geven de gemiddelde waarden per item weer die op de vijfpunts Likertschaal zijn gescoord.
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Abstract: Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.
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