86 research outputs found
Imaging in-stent restenosis: an inexpensive, reliable, and rapid preclinical model.
Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and future drug-eluting stents. A variety of antibodies and transgenic and knockout strains are available in rats. Consequently, a model for in-stent restenosis in the rat would be convenient for pathobiological and pathophysiological studies. In this video, we present the full procedure and pit-falls of a rat stent model suitable for high throughput stent research. We will show the surgical procedure of stent deployment, and the assessment of in-stent restenosis using the most elegant technique of OCT (Optical Coherence Tomography). This technique provides high accuracy in assessing plaque CSAs (cross section areas) and correlates well with histological sections, which require special and time consuming embedding and sectioning techniques. OCT imaging further allows longitudinal monitoring of the development of in-stent restenosis within the same animal compared to one-time snapshots using histology
Heterotopic and Orthotopic Tracheal Transplantation in Mice used as Models to Study the Development of Obliterative Airway Disease
Obliterative airway disease (OAD) is the major complication after lung transplantations that limits long term survival (1-7)
Entwicklung und technische Integration einer Bewertungsmethodik zur Ermittlung von Mitarbeiterbelastungen in Kommissioniersystemen (ErgoKom)
Ziel des Forschungsprojekts ErgoKom war die Entwicklung einer Methodik zur aufwandsarmen Bewertung der tatsĂ€chlich vorliegenden Mitarbeiterbelastung unter BerĂŒcksichtigung der speziellen Anforderungen der Kommissionierung. Durch die Integration und Implementierung technischer Hilfsmittel, wie Motion Capturing und industrieller Sensoren, wird eine automatisierte, fortlaufende Belastungserfassung, Risikobewertung und Visualisierung ermöglicht. Zudem wird erlĂ€utert, wie differenzierte ArbeitsgestaltungsmaĂnahmen zur Neuplanung ergonomisch gĂŒnstiger sowie zur Optimierung bestehender Kommissioniersysteme abgeleitet werden können. Die Anwendung der Methodik ermöglicht die Reduktion langfristiger gesundheitlicher SchĂ€digungen im Kontext der aufgrund des demographischen Wandels verĂ€nderten GröĂe und Zusammensetzung des Erwerbspersonenpotenzials
Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade
Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40âmg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients
Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients
Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach. Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell potential and differentiation capacity. Endothelial cells, smooth muscle cells, and cardiomyocytes derived from hypoimmunogenic mouse or human iPSCs reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression. These findings suggest that hypoimmunogenic cell grafts can be engineered for universal transplantation
Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study
The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current LAS era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N=3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% †45 years, p<0.0001), were less often smokers (35% vs. 46%, p<0.0001), had more often clear chest X-rays (82% vs. 72%, p<0.0001), had better donor oxygenation ratio's (20% vs. 26% with PaO /FiO †300 mmHg, p<0.0001) and had better lung donor score values (LDS) (28% vs. 17% with LDS=6, p<0.0001) compared to donors used for LTx in countries with low donation rate. Survival rates for the groups LDS =6 and â„7 at 5 years were 69.7% and 60.9% (p=0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized
Minimal access median sternotomy for aortic valve replacement in elderly patients
BACKGROUND: We report our clinical experience with a approach for aortic valve replacement (AVR) via minimal access skin incision and complete median sternotomy. This approach was used in patients with higher age and multiple co-morbidities, facilitating an easy access with short bypass and cross clamp times. It was especially performed in patients asking for an excellent cosmetic result, who did not qualifying for minimally-invasive AVR via partial upper sternotomy. METHODS: AVR via minimal-access median sternotomy, was performed in 58 patients between 01/2009 and 11/2011. Intra- and postoperative data including cross clamp time, cardiopulmonary bypass time, mortality, stroke, pacemaker implantation, re-operation for bleeding, ventilation time, ICU and hospital stay, wound infection, sternal dehiscence or fracture and 30 day mortality were collected. RESULTS: Mean patients age was 76.1 +/â9.4 years, 72% were female. Minimal-access AVR could be performed with a mean length of midline skin incision of 7.8 cm. Aortic cross-clamping time was 54.6 +/â6.3 min, cardiopulmonary bypass time 71.2+/â11.3 min and time of surgery 154.1 +/â26.8 min. Re-operation for bleeding had to be performed in 1 case (1.7%). There were no strokes or pacemaker implantations needed. Mean ventilation time was 4.5 h, ICU stay was 2 days and mean length of hospital stay was 6 days. 6 months follow up showed mortality of 0% and no sternal dehiscence or wound infection was observed. CONCLUSION: Minimal-access AVR via complete median sternotomy can be performed safely,in this elderly patient cohort without adding additional operative risk compared to conventional AVR. By avoidiance of large skin incisions this approach combines excellent cosmetic results with fast surgery time and excellent postoperative recovery
Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant â a historical prospective study
The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% â€45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 â€Â 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and â„7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized
Lung allocation score: The Eurotransplant model versus the revised US model - a cross-sectional study
Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET
Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice.
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