Kardiale Spätschäden der Diphtherie

Bei echokardiographischen Routine-Untersuchungen fiel bei Patienten mit einer lange zurückliegenden DiphtherieErkrankung eine beidseitige Vorhofvergrößerung auf, ohne daß eine weitere zugrunde liegende Herzerkrankung erkennbar war. Derartige Veränderungen wurden bisher in der Fachliteratur nicht beschrieben. Die vorliegende Studie wurde durchgeführt um der Frage nachzugehen, ob nach einer Diphtherieerkrankung in der Jugend im höheren Lebensalter signifikante Spätschäden am Herzen faßbar sind. Die hierzu durchgeführten Untersuchungen waren ein EKG, eine Röntgenuntersuchung des Thorax, die Echokardiographie und Phonomechanokardiographie. Im Rahmen des normalen Krankenhausbetriebes wurden 50 Patienten erfaßt, die eine entsprechende Diphtherieanamnese hatten. Bei keinem dieser Patienten war anamnestisch zum Zeitpunkt der akuten Erkrankung eine Diphtheriemyokarditis nachgewiesen worden. Diese Patienten wurden einem bezüglich der Begleiterkrankungen und der Altersstruktur vergleichbaren Kontrollkollektiv gegenübergestellt. Bei der Röntgenuntersuchung des Thorax war kein pathologischer Befund zu erheben, der für die beschriebenen regelmäßigen Veränderungen als Erklärung dienen kann.. Das EKG zeigte keine einheitlichen Formveränderungen, jedoch in der Diphtheriegruppe einen mit 20% hohen Anteil von Patienten mit Vorhofflimmern. Die Ausbildung einer diastolischen Relaxationsstörung der Ventrikel, die sich dopplerechokardiographisch anhand des VE/VA-Verhältnisses nachweisen lässt, stellt den zentralen Befund dar. Auch bei der Mechanokardiographie liegen in Form einer hohen A-Welle Hinweise für eine diastolische Dehnbarkeitsstörung vor. Diese Dehnbarkeitsstörung, die in der Diphtheriegruppe bei 80% der Patienten nachweisbar ist, entsteht möglicherweise dadurch, daß es im Rahmen der akuten Diphtherie durch eine interstitielle Myokarditis zu einer Destruktion von Herzmuskelfasern mit Ausbildung kleiner Narbenherde kommt. Die chronische Druckbelastung der Vorhöfe führt dann im Laufe der Jahre zu der beobachteten allmählichen Vorhofvergrößerung, wobei zusätzliche belastende Faktoren wie eine arterielle oder pulmonalarterielle Hypertonie den Effekt verstärken. Der hohe Anteil von Patienten mit Vorhofflimmern innerhalb der Diphtheriegruppe gegenüber dem Kontrollkollektiv läßt sich folglich durch die beschriebene Vorhofvergrößerung erklären, zum anderen aber auch durch eine direkte Schädigung der Vorhofmuskulatur durch die Toxinwirkung mit der Folge einer Fibrosierung des Myokards.In echocardiographic routine-examination some patients, who have had a diphtheria during childhood were noticed to have a biatrial enlargement, without a concurring heart failure. Such pathologic changesas a complication of a diphtheria has not been described before. This study was initiated to determine late cardiac disorders after a diphtheria. Examinations included an ECG, Chest-X-Ray, echocardiography and polymechanocardiography. In this study 50 patients were included, who had a diphtheria in past. None of the patients had a myocarditis at the same time as acute diphtheria. They were compared to 50 patients, who had not had a diphtheria in history. Chest X-ray showed no significant pathology. In ECG a high incidence of patients ( 20% ) with atrial fibrillation was noticed. In echocardiography the developement of a ventricular diastolic relaxation pattern of the mitral inflow is the main observation. A similar observation is a high A-wave in mechanocardiography. The diastolic relaxation-pattern is seen in 80% of the patients with a diphtheria in youth. It may be a sequel of a interstitiell myocarditis while acute diphtheria with destruction of single muscle fibres and development of a fibrosis. Over the years chronic pressure may lead to the seen biatrial enlargement Additional factors as increased blood pressure amplifies the effect. The high incidence of patients with atrial fibrillation in the group of patients who had a diphtheria may be explained by the atrial enlargement itself as well as by the mild fibrosis after toxin-induced destruction of single muscle fibres in diphtheric myocarditis

Hvad er effekten af ren-luftzoner for luftforureningen i København?

Ren-luftzoner, hvor der stilles højere miljøkrav til køretøjer inden for et geografisk område, er et muligt virkemiddel til at forbedre luftkvaliteten i de større byer og til at reducere antallet af overskridelser af grænseværdien for kvælstofdioxid (NO2). Ren-luftzoner er et nyt ord for miljøzoner. Det nye ved ren- luftzoner er, at de stiller miljøkrav til ældre person- og varebiler, og ikke kun som de eksisterende miljøzoner til lastbiler og busser. Denne artikel vurderer effekten af forskellige udformninger af ren- luftzoner, og hvilken betydning det har for emission og luftkvalitet i 2013, 2015 og 2017 med udgangspunkt i scenarieberegninger gennemført i 2012. Dette sker med udgangspunkt i H.C. Andersens Boulevard i København, hvor NO2 grænseværdien er overskrevet. Den mest vidtgående ren-luftzone beskrevet i denne artikel vil føre til en beregnet reduktion i NOx emissionen på knap 13% svarende til en reduktion af NO2 koncentrationen på knap 3 μg/m3 i 2015

Apparent Temperature and Cause-Specific Mortality in Copenhagen, Denmark: A Case-Crossover Analysis

Temperature, a key climate change indicator, is expected to increase substantially in the Northern Hemisphere, with potentially grave implications for human health. This study is the first to investigate the association between the daily 3-hour maximum apparent temperature (Tappmax), and respiratory, cardiovascular and cerebrovascular mortality in Copenhagen (1999–2006) using a case-crossover design. Susceptibility was investigated for age, sex, socio-economic status and place of death. For an inter-quartile range (7 °C) increase in Tappmax, an inverse association was found with cardiovascular mortality (−7% 95% CI −13%; −1%) and none with respiratory and cerebrovascular mortality. In the cold period all associations were inverse, although insignificant

Pharmacological inhibition of protein tyrosine kinases axl and fyn reduces TNF-α-induced endothelial inflammatory activation in vitro

Major surgery induces systemic inflammation leading to pro-inflammatory activation of endothelial cells. Endothelial inflammation is one of the drivers of postoperative organ damage, including acute kidney injury Tumour Necrosis Factor alpha (TNF-α) is an important component of surgery-induced pro-inflammatory activation of endothelial cells. Kinases, the backbone of signalling cascades, can be targeted by pharmacological inhibition. This is a promising treatment option to interfere with excessive endothelial inflammation. In this study, we identified activated kinases as potential therapeutic targets. These targets were pharmacologically inhibited to reduce TNF-α-induced pro-inflammatory signalling in endothelial cells. Kinome profiling using PamChip arrays identified 64 protein tyrosine kinases and 88 serine-threonine kinases, the activity of which was determined at various timepoints (5–240 min) following stimulation with 10 ng/ml TNF-α in Human umbilical vein endothelial cells in vitro. The PTKs Axl and Fyn were selected based on high kinase activity profiles. Co-localisation experiments with the endothelial-specific protein CD31 showed Axl expression in endothelial cells of glomeruli and Fyn in arterioles and glomeruli of both control and TNF-α-exposed mice. Pharmacological inhibition with Axl inhibitor BMS-777607 and Fyn inhibitor PP2 significantly reduced TNF-α-induced pro-inflammatory activation of E-selectin, VCAM-1, ICAM-1, IL-6 and IL-8 at mRNA and VCAM-1, ICAM-1, and IL-6 at protein level in HUVEC in vitro. Upon pharmacological inhibition with each inhibitor, leukocyte adhesion to HUVEC was also significantly reduced, however to a minor extent. In conclusion, pre-treatment of endothelial cells with kinase inhibitors BMS-777607 and PP2 reduces TNF-α-induced endothelial inflammation in vitro

TOOL FOR EXPLORATORY ANALYSIS OF OSPM MODEL PERFORMANCE FOR LONG TIME SERIES

Abstract: The Danish Operational Street Pollution Model, OSPM, has for two decades been successfully applied in many cities worldwide as recently reviewed by Key words: model validation, street canyon, urban air pollution, OSPM, exploratory data analysis. INTRODUCTION The OSPM (Operational Street Pollution Model) has been evaluated and applied by a wide range of users worldwide (see: Kakosimos et al. 2010) for modelling urban air pollution at street level. Proper model validation protocols and best modelling practise have been discussed in the scientific community for many years, lately in the COST 732 action (URL 1) and in the Forum for Air quality Modelling in Europe (FAIRMODE, URL 2). A document produced by COST 732 provides general guidance on model evaluation protocols (Britter and Schatzmann, 2007). Model validation is also relevant in context of the European Air Quality Directive (EC, 2008) that is mentioning models as a method to assess air quality with respect to compliance with limit values. The directive defines some model quality objectives that are now interpreted and discussed within FAIRMODE, and performed tests have revealed some ambiguities in the interpretation of those objectives (e.g. Gidhagen at al. 2011). This paper aims at contributing to the discussion. Model quality objectives are in the directive as in other guidelines formulated in terms of quantitative statistical analysis, e.g. maximum uncertainty presented for the annual average or for percentiles. However this statistical analysis might obscure deficiencies of the model, and model results could be "right for the wrong reason", i.e. the model quality objective might be fulfilled even if the model fails to reproduce some essential features in observations. Therefore Di Sabatini et al. (2008) recommended for the case of CFD models a combination of qualitative (exploratory data analysis) and quantitative (statistical analysis) evaluations. The usefulness in identifying model errors by means of qualitative data analysis using an automated Excel workbook was presented by Olesen et al. (2008). This work focuses on the evaluation of OSPM and presents a similar approach suggesting a combined evaluation strategy of qualitative and quantitative analysis. Even though OSPM is a parameterised semi-empirical model with much simpler physics compared to the CFD models this evaluation strategy is applicable. This approach and the here presented Excel evaluation tool can easily be used also by other models of this type

Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects

AbstractThis cross-sectional study investigated the relationship between exposure to airborne indoor and outdoor particulate matter (PM) and cardiovascular and respiratory health in a population-based sample of 58 residences in Copenhagen, Denmark. Over a 2-day period indoor particle number concentrations (PNC, 10–300nm) and PM2.5 (aerodynamic diameter<2.5μm) were monitored for each of the residences in the living room, and outdoor PNC (10–280nm), PM2.5 and PM10 (aerodynamic diameter<10μm) were monitored at an urban background station in Copenhagen. In the morning, after the 2-day monitoring period, we measured microvascular function (MVF) and lung function and collected blood samples for biomarkers related to inflammation, in 78 middle-aged residents. Bacteria, endotoxin and fungi were analyzed in material from electrostatic dust fall collectors placed in the residences for 4weeks. Data were analyzed using linear regression with the generalized estimating equation approach. Statistically significant associations were found between indoor PNC, dominated by indoor use of candles, and lower lung function, the prediabetic marker HbA1c and systemic inflammatory markers observed as changes in leukocyte differential count and expression of adhesion markers on monocytes, whereas C-reactive protein was significantly associated with indoor PM2.5. The presence of indoor endotoxin was associated with lower lung function and expression of adhesion markers on monocytes. An inverse association between outdoor PNC and MVF was also statistically significant. The study suggests that PNC in the outdoor environment may be associated with decreased MVF, while PNC, mainly driven by candle burning, and bioaerosols in the indoor environment may have a negative effect on lung function and markers of systemic inflammation and diabetes

Apparent Temperature and Cause-Specific Emergency Hospital Admissions in Greater Copenhagen, Denmark

One of the key climate change factors, temperature, has potentially grave implications for human health. We report the first attempt to investigate the association between the daily 3-hour maximum apparent temperature (Tappmax) and respiratory (RD), cardiovascular (CVD), and cerebrovascular (CBD) emergency hospital admissions in Copenhagen, controlling for air pollution. The study period covered 1 January 2002−31 December 2006, stratified in warm and cold periods. A case-crossover design was applied. Susceptibility (effect modification) by age, sex, and socio-economic status was investigated. For an IQR (8°C) increase in the 5-day cumulative average of Tappmax, a 7% (95% CI: 1%, 13%) increase in the RD admission rate was observed in the warm period whereas an inverse association was found with CVD (−8%, 95% CI: −13%, −4%), and none with CBD. There was no association between the 5-day cumulative average of Tappmax during the cold period and any of the cause-specific admissions, except in some susceptible groups: a negative association for RD in the oldest age group and a positive association for CVD in men and the second highest SES group. In conclusion, an increase in Tappmax is associated with a slight increase in RD and decrease in CVD admissions during the warmer months