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Background: Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers. Aim: To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection. Methods: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes. Results: In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (< 50 nmol/liter) was present in 59% and hypoalbuminemia (< 3.5 g/dL) in 55% of the study patients. Low serum albumin level was associated to one, two- and five-year mortality after hospital stay (all P <.05). In addition, it was associated with pneumonia, dyspnea, over 13-night long stay at ward and death at ward (all P < .05). No associations were seen between serum 25(OH)D and LL-37 levels and disease severity, short-term clinical outcome, or long-term survival. Associations between serum 25(OH)D, albumin, and LL-37 levels and respiratory virus presence were not seen. Conclusions: Serum albumin level on admission seems to give valuable information about the patients’ general health and recovery potential in treating older adults with respiratory symptoms. Se

In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95% C

Beschrijving van de grote bluetongue-epidemie bij rundvee en schapen in Noordwest-Europa van 2006. De epidemie werd veroorzaakt door het bluetongue-virusserotype 8 (BTV-8). Morbiditeit en mortaliteit waren aanzienlijk hoger op bedrijven met schapen dan op bedrijven met rundvee, Epidemiology of Bluetongue virus serotype 8 outbreaks in the Netherlands in 2006. In August 2006 a major epidemic of Bluetongue (bt) occurred in north-western Europe, affecting the Netherlands, Belgium, Germany, Luxemburg, and the north of France. It was caused by bt virus serotype 8 (btv-8), a serotype previously unknown to the eu. Although clinical disease is usually restricted to sheep, this virus also caused clinical disease in a small proportion of cattle. The last clinical outbreak of bt in the Netherlands occurred mid-December 2006. The delay between observation of the first clinical signs by the owner and reporting of a clinically suspect bt situation to the veterinary authorities was approximately 2 weeks. btv-8-associated clinical signs were more prominent in sheep than in cattle, and the relative frequency of specifi c clinical signs was different in cattle and sheep. Morbidity and mortality rates were signifi cantly higher among sheep than among cattle, and a higher proportion of cattle than sheep recovered from clinical disease

Contains fulltext : 48654.pdf (publisher's version ) (Closed access), Despite loss of centrally mediated sympathetic vasoconstriction to the legs, spinal cord-injured individuals cope surprisingly well with an orthostatic challenge. This study assessed changes in leg vascular resistance following head-up tilt in healthy (C) and in paraplegic (P) individuals. After 10 min of supine rest, subjects were tilted 30 degrees head-up. Mean arterial pressure (MAP) and total peripheral resistance (TPR) increased in C (MAP from 76.7 +/ -6.6 mmHg to 80.6 +/- 8.2 mmHg; TPR from 1.12 +/- 0.26 AU to 1.19 +/ -0.31 AU) while both remained unchanged in P. Echo Doppler ultrasound determined red blood cell velocity in the femoral artery, which decreased (P from 18.9+/-6.2 cm/s to 12.5 +/- 4.5 cm/s, P = 0.001; C from 16.3 +/- 6.2 cm/s to 10.8 +/- 5.0 cm/s, P = 0.001) and leg vascular resistance, which increased (P from 402 +/- 137 AU to 643 +/- 274 AU, P = 0.001; C from 238 +/- 68 AU to 400 +/- 122 AU, P = 0.003) from supine to upright. The present study shows that independent of supraspinal sympathetic control, humans are able to increase leg vascular resistance and maintain blood pressure during head-up tilt.

Contains fulltext : 48900.pdf (publisher's version ) (Closed access), Despite the loss of centrally mediated sympathetic vasoconstriction, spinal cord-injured (SCI) individuals cope surprisingly well with orthostatic challenges. In the pathophysiology of this intriguing observation spinal sympathetic-, veno-arteriolar-(VAR), and myogenic reflexes seem to play a role. The purpose of this study was to assess whether central (stroke volume, heart rate, blood pressure and total peripheral resistance) and peripheral (leg blood flow, leg vascular resistance and femoral arterial diameter) hemodynamic responses to head-up tilt are different in two groups of SCI patients, i. e., SCI individuals with upper motor neuron lesions (who have spinal reflexes, VAR and myogenic reflexes) (U; n=6) and those with lower motor neuron lesion (who have no spinal reflexes, perhaps no VAR due to nerve degeneration, but intact myogenic reflexes) (L; n=5). Ten healthy male individuals served as controls (C) (normal supraspinal sympathetic control and presence of all reflexes). After 10 min supine rest all individuals were tilted to 30 degrees head-up tilt. Red blood cell velocity (measured by echo Doppler ultrasound) in the femoral artery decreased and vascular resistance increased significantly in all three groups in the upright position compared with supine. Mean arterial pressure (MAP) remained unchanged in U and L and increased significantly in C in the upright versus supine position. The present study shows that all SCI individuals were able to maintain MAP by increasing leg vascular resistance during head-up tilt, despite nerve degeneration in L and lack of centrally mediated sympathetic control in all SCI individuals. Results of the present study suggest that not spinal reflexes but local (myogenic) reflex activity plays a pivotal role in peripheral vascular responses upon head-up tilt when central control mechanisms fail.

Contains fulltext : 141676.pdf (publisher's version ) (Closed access), STUDY DESIGN: Observational cross-sectional study. OBJECTIVE: To assess the vascular characteristics of the arterial circulation in individuals with spina bifida (SB) in comparison with individuals with spinal cord injury (SCI) and able-bodied controls (C). SETTING: University Medical Centre, Nijmegen, The Netherlands. METHODS: Six spina bifida (SB), 15 spinal cord injury (SCI) and 10 C were included. Red blood cell velocities and arterial diameter of the common carotid artery and common femoral artery were measured using echo-Doppler ultrasound in a supine position. A venous blood sample was withdrawn for determination of blood viscosity. RESULTS: In the common carotid artery, blood flow and wall shear stress were not different between the three groups. The diameter was smaller in SB compared with SCI and C. In the common femoral artery, blood flow was smaller in SB than in SCI and C. Wall shear stress was significantly higher in SB and SCI compared with C. High wall shear stress may lead to endothelial dysfunction and related cardiovascular disease. CONCLUSION: Deteriorating vascular properties are present in SB as well as in spinal-cord-injured individuals in comparison with C. These properties tend to be more pronounced in SB than in SCI.

Item does not contain fulltext, OBJECTIVES: Erectile dysfunction (ED) is a common disorder of aging male and about 50% of the ED sufferers consult a physician in the Netherlands. As ED is strongly correlated with cardiovascular diseases, we explored how many patients with ED aged 40 to 69 years will develop cardiovascular disease in the Netherlands and, philosophize if and which preventive measures are available to reduce cardiovascular risks in this specific population. METHODS: 158 patients were included and were comprehensively evaluated. All patients underwent a penile-pharmaco duplex ultrasonography to evaluate the penile vascular status and a cut-off value for acceleration time of 100 ms was used to distinguish between patients with and without cavernous arterial insufficiency. Framingham risk functions were used to determine the 4 to 12 year coronary heart disease risk. The results were extrapolated to the Dutch ageing male population. RESULTS: In the age group 40 to 49 years and 60 to 69 years no significant difference was detected in coronary heart disease risk between patients with and without cavernous arterial insufficiency. In the age group 50 to 59 years patients with cavernous arterial insufficiency showed a significantly increased risk to develop coronary heart disease. It is estimated that in total, more than 25,000 ageing men with ED will develop coronary heart disease within 4 years and increases to almost 75,000 men within 12 years in the Netherlands. CONCLUSIONS: Screening on cardiovascular risk factors and taking preventive measures is recommended in men with ED. Men with cavernous arterial insufficiency aged 50 to 59 years are especially prone to develop coronary artery disease.

Item does not contain fulltext, A total of 76 male patients on renal replacement therapy (RRT) were investigated. Erectile dysfunction (ED) was defined as insufficient erection during visual erotic stimulation (VES) or during sleep as measured with Rigiscan and Erectiometer. Data on medical history, physical examination, and laboratory variables were collected. Furthermore, penile pharmacological duplex ultrasonography (PPDU) was performed. Univariate and multivariate logistic regressions were used to determine prognostic values and to develop prognostic models. Independent prognostic factors for ED were the number of cardiovascular events, waist-hip ratio, body mass index, and acceleration time (AT) as measured with PPDU. Independent prognostic factors for an abnormal AT (>100 ms) were number of cardiovascular events, age category, and the presence of carotid bruits. Independent prognostic factors for insufficient veno-occlusion during PPDU were number of cardiovascular events and supine diastolic blood pressure. The vascular contribution to ED in patients on RRT is substantial. Data from medical history, limited physical examination, and PPDU contribute to the prediction of the vascular contribution to ED.

Item does not contain fulltext, PURPOSE: We revalidate parameters of the cavernous arterial response (peak systolic blood flow velocity) and acceleration time using penile duplex pharmaco-ultrasonography. MATERIALS AND METHODS: Blood flow velocity in the cavernous artery following pharmaco-stimulation was determined with duplex ultrasonography in 106 patients with erectile dysfunction. Intima media thickness of the common carotid artery, a valid index for atherosclerosis and clinical diagnosis based on a comprehensive evaluation were used as references. The clinical diagnosis was used to determine cutoff values. For the statistical analysis, Pearson correlation and ROC curves were used. RESULTS: When correlating peak systolic velocity and acceleration time to intima media thickness, acceleration time (r = 0.51, p <0.01) was the most valid parameter to detect cavernous atherosclerotic pathology (peak systolic velocity r = -0.18, p = 0.12). This finding was confirmed by a comparison of both parameters to the clinical diagnosis. AUC was 0.59, 95% CI 0.49-0.69 for peak systolic velocity and 0.72 (95% CI 0.62-0.80 for acceleration time). The cutoff point for acceleration time to discriminate between atherosclerotic and nonatherosclerotic erectile dysfunction was determined at acceleration time 100 milliseconds or greater. Sensitivity was 66% and specificity was 71%. CONCLUSIONS: The results of this study show that acceleration time has more power than peak systolic velocity to diagnose atherosclerotic erectile dysfunction.

Contains fulltext : 141688.pdf (publisher's version ) (Closed access), The purpose of this study was to assess the relationship between inactivity and shear stress, the frictional force of blood against the endothelium, in spinal cord injury (SCI) subjects. SCI group offers a unique "model of nature" to study the effects of inactivity. Nine SCI subjects with upper (SCI-U) and 5 with a lower (SCI-L) motoneuron lesion and 10 able-bodied controls (C) were included. A venous blood sample was withdrawn to determine blood viscosity. Red blood cell velocities and arterial diameters of the common carotid artery (CCA) and common femoral artery (CFA) were measured by using echo-Doppler ultrasound in a supine position. No differences were observed in wall shear stress in the CCA between groups. In the CFA, peak and mean wall shear stress were significantly increased in SCI (14.1 and 1.2 Pa, respectively) compared with C (10.2 and 0.9 Pa, respectively). Because SCI-U and SCI-L showed no differences in shear stress levels, inactivity and not nerve degeneration seems to cause the elevated shear stress levels in the CFA in SCI. However, the lack of central neural control as a causal factor cannot be ruled out.

Contains fulltext : 212688.pdf (publisher's version ) (Closed access), OBJECTIVE: Postthrombotic syndrome (PTS) develops in 40% to 60% of patients with deep venous thrombosis. Factors that are important in the development of PTS include venous reflux, deep vein obstruction, and calf muscle pump dysfunction (CMD). METHODS: Reflux and CMD in relationship to the severity of PTS were evaluated in a 2-year follow-up study of patients with acute deep venous thrombosis. Duplex scanning was used to measure reflux. The supine venous pump function test (SVPT) measures CMD with strain-gauge plethysmography. The base-line examination was performed within 1 to 5 days after diagnosis. The next examinations were scheduled at 3, 6, 12, and 24 months. RESULTS: The study included 86 legs, and the 2-year follow-up period was completed for 70 legs. Significantly more reflux was found in previously thrombosed vein segments, with an odds ratio of 1.8 after 3 months, of 2.1 after 6 months, of 2.5 after 12 months, and of 3.2 after 24 months. Multiple regression results showed that the most important risk factor for early clinical signs of PTS was superficial reflux in months 3, 6, and 12 (P < or =.02). Deep reflux did not have a synergistic relationship with superficial reflux in correlation with the clinical signs of PTS. The SVPT was not able to predict the development of PTS. CONCLUSION: More reflux develops in previously thrombosed vein segments. As early as after the third month, patients with superficial reflux have an increased risk of development of the first clinical signs of PTS. Within 2 years, the SVPT shows no relationship with clinical signs of PTS.

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Item does not contain fulltext, OBJECTIVE: In patients with severe heart failure, compensatory mechanisms fail to provide adequate blood supply to the peripheral circulation, especially when the metabolic need is increased. The aim of this study was to assess alterations in the peripheral circulation in patients with mild heart failure using ultrasound Doppler. METHODS: In 19 controls and in 11 patients with mild heart failure, Doppler spectra were recorded from the carotid, the brachial and the femoral artery at rest and, from the latter two arteries, during post-occlusive reactive hyperemia. Parameters derived from these Doppler spectra were used to make comparisons between both groups. RESULTS: At rest, the duration of the acceleration of blood was shorter in controls, the acceleration was steeper in controls and the deceleration duration was longer in controls as compared to the patients. Differences in the response to reactive hyperemia were only observed in the common femoral artery. CONCLUSIONS: In patients with mild heart failure, significant alterations in the peripheral circulation were observed especially for the femoral artery. These changes are caused by the impairment of the left ventricular function and by adjustments in the compensatory mechanism of the peripheral circulation.

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UMC St Radboud, 15 november 2000, Promotores : Skotnicki, S.H., Thien, Th. Co-promotores : Wollersheim, H.C.H., Langen, H. van, Item does not contain fulltext

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UMC St Radboud, 20 december 2000, Promotores : Thien, Th., Stalenhoef, A.F.H. Co-promotores : Wollersheim, H.C.H., Langen, H. van, Item does not contain fulltext

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