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Didier A.,Rangueil Larrey Hospital | Worm M.,Universitaetsmedizin Berlin | Horak F.,Allergy Center Vienna West | Sussman G.,University of Toronto | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. Objectives: We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis. Methods: Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. Results: The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P <.0001 for both). Reductions were observed in total symptom scores and ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. Conclusions: Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons. © 2011 American Academy of Allergy, Asthma & Immunology.

Burghardt A.J.,University of California at San Francisco | Issever A.S.,University of California at San Francisco | Issever A.S.,Universitaetsmedizin Berlin | Schwartz A.V.,University of California at San Francisco | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone mineral density (BMD). Objective: In this study, high-resolution peripheral quantitative computed tomography was applied to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM. Design and Setting: A cross-sectional study was conducted in patients with T2DM recruited from a diabetic outpatient clinic. Participants: Elderly female patients (age, 62.9 ± 7.7 yr) with a history of T2DM (n = 19) and age-and height-matched controls (n = 19) were recruited. Outcome Measures: Subjects were imaged using high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by micro-finite element analysis. Results: Compared to the controls, the T2DM cohort had 10% higher trabecular volumetric BMD (P < 0.05) adjacent to the cortex and higher trabecular thickness in the tibia (13.8%; P < 0.05). Cortical porosity differences alone were consistent with impaired bone strength and were significant in the radius (>+50%;P < 0.05), whereas pore volume approached significance in the tibia (+118%;P = 0.1). Conclusion: The results of this pilot investigation provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM. The findings suggest that T2DM may be associated with impaired resistance to bending loads due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density. Copyright © 2010 by The Endocrine Society.

Werncke T.,Charité - Medical University of Berlin | Von Falck C.,Hannover Medical School | Wittmann M.,Institute For Diagnostische Und Interventionelle Radiologie | Elgeti T.,Universitaetsmedizin Berlin | And 2 more authors.
European Radiology | Year: 2013

Objectives: To assess the influence of different table feeds (TFs) on vascular enhancement and image quality in patients with an abdominal aortic aneurysm (AAA) undergoing computed tomography (CT) angiography of the lower extremities (run-off CTA). Methods: Seventy-nine patients (71 ± 8 years) with an AAA (>30 mm) who underwent run-off CTA between January 2004 and August 2011 were included in this retrospective institutional review board-approved study. Run-off CTA was conducted using 16- and 64-row CT. The range of TFs was 30-86 mm/s and was categorised in quartiles TF1 (32.6 ± 1.9 mm/s), TF2 (38.9 ± 0.9 mm/s), TF3 (43.9 ± 3.1 mm/s) and TF4 (57.4 ± 10.5 mm/s). Image quality was rated independently by two radiologists and vessel enhancement was assessed. Results: Image quality was diagnostic at all aortic, pelvic and almost all thigh levels. Below the knee, the number of diagnostic levels was highest for TF1 and decreased to TF4. Arterial enhancement between the aorta and fibular trunk was not different in all TF groups, P > 0.05. At the calf and foot strongest arterial enhancement was noted for TF1 and TF2 and decreased to TF4, P < 0.01. Conclusion: Results indicate that the highest image quality of run-off CTA in patients with an AAA may be obtained using table feeds measuring 30-35 mm/s. Key Points: • CTA has become a key investigation for peripheral vascular disease. • Run-off CTA is more complex in patients with an abdominal aortic aneurysm. • Run-off CTA is feasible with a short bolus of intravenous contrast medium. • A constant 30-35 mm/s table feed provides the highest likelihood of diagnostic images. © 2013 European Society of Radiology.

Schilling R.,Universitaetsmedizin Berlin | Jastram B.,TU Berlin | Wings O.,Leibniz Institute for Evolution and Biodiversity Research | Schwarz-Wings D.,Leibniz Institute for Evolution and Biodiversity Research | Issever A.S.,Universitaetsmedizin Berlin
Radiology | Year: 2014

Purpose: To demonstrate the feasibility of using computed tomography (CT) to confirm the identity of an unprepared fossil and to use the CT dataset to separate the fossilized bone from its surrounding sediment matrix and produce a three-dimensional (3D) print. Materials and Methods: The examined object was a plaster jacket containing an unprepared fossil. CT was performed with a 320-section multidetector unit. A marching cube-based method was used to transform the voxel CT dataset into triangle-based, editable geometry. Then, a comprehensive postprocessing step was performed to isolate the geometry of the vertebra from its surrounding fossilized matrix. Finally, the resulting polygon mesh describing only the vertebra was used for a physical 3D reconstruction by using a selective laser sintering machine. Results: The CT examination provided enough data to assign the fossil to the genus Plateosaurus. In addition, much valuable information about the fossil has been gained-in particular the visualization of multiple fractures and the destruction of the anterior rim of the vertebral body. Finally, the results show that the 3D print generated, including the fractures and the anterior destruction, may be considered an accurate copy of the bone with the unprepared fossil. Conclusion: The authors demonstrated the feasibility and potential utility of combining CT with 3D printing, providing a nondestructive method to future paleontologists. © 2014 RSNA.

Kalb R.,Heinrich Heine University Düsseldorf | Kram R.,Heinrich Heine University Düsseldorf | Morgera S.,Universitaetsmedizin Berlin | Slowinski T.,Universitaetsmedizin Berlin | Kindgen-Milles D.,Heinrich Heine University Düsseldorf
Therapeutic Apheresis and Dialysis | Year: 2013

Acute kidney injury requiring renal replacement therapy occurs in up to 10% of all intensive care unit patients. Those who are hemodynamically unstable are often treated with continuous renal replacement therapy requiring continuous anticoagulation of the extracorporeal circuit. This is usually achieved by infusion of unfractionated heparin, which subsequently increases the risk of bleeding. To avoid systemic anticoagulation for continuous renal replacement therapy, regional anticoagulation with citrate has been introduced. We studied safety and efficacy of regional citrate anticoagulation for continuous venovenous hemodialysis in surgical patients requiring high dialysis doses. This was an observational prospective study in a 40-bed surgical intensive care unit at a university hospital. During a 12-month study period, all consecutive critically ill patients with high risk of bleeding requiring continuous renal replacement therapy continuous renal replacement therapy were treated with citrate anticoagulation for continuous venovenous hemodialysis. Prescribed dialysis dose was 45mL/kg per h with a 10% increase for expected downtime. We studied filter lifetime, delivered dialysis dose, control of acid-base status, bleeding episodes, and adverse effects, that is, citrate intolerance. The total number of filters analyzed in 75 patients was 100. Mean (±standard deviation) filter running time was 78±25h. Fifty-one circuits had to be renewed because of extended filter running time (96±18h), 33 discontinued for reasons not related to renal replacement therapy (62±19h), and 13 due to filter clotting (58±18h). The mean dialysis dose during the first 72h was 49±14mL/kg per h. Overall, acid-base status after 72h was well controlled in 62% of patients, metabolic alkalosis (pH>7.45) occurred in 29%, and metabolic acidosis (pH<7.35) in 9%. In one patient, treatment was stopped because of citrate accumulation. Citrate intoxication or overt bleeding episodes were not observed. Regional citrate anticoagulation for continuous venovenous hemodialysis is a safe and effective method to deliver a high dialysis dose in critically ill patients with a high risk of bleeding. Filter patency was excellent, acid-base status was well controlled, and clinically relevant adverse effects were not observed. Therefore, citrate anticoagulated continuous venovenous hemodialysis is a useful treatment option for patients with acute kidney injury requiring high dialysis doses and at risk of bleeding. © 2012 International Society for Apheresis.

Mochales C.,University of Barcelona | Mochales C.,Universitaetsmedizin Berlin | Wilson R.M.,University of London | Dowker S.E.P.,Queen Mary, University of London | Ginebra M.-P.,University of Barcelona
Journal of Alloys and Compounds | Year: 2011

Dry mechanosynthesis is an efficient technique to synthesise nanocrystalline calcium deficient hydroxyapatites (CDHA). The mechanisms underlying a mechanochemical reaction are different from those triggering a dissolution mediated process, and this can have an effect on the structural features of the product. In this work, a nanocrystalline CDHA with Ca/P molar ratio of 1.5 obtained by means of dry mechanosynthesis of calcium oxide and dicalcium phosphate dihydrate was analysed. Spectroscopic techniques confirmed the presence of hydrogen phosphate (HPO 4 2-) groups and a non-apatitic environment of the phosphate ions and disordered hydroxyl groups due to the nanometric size of the crystals. Lattice parameters of mechanosynthesised CDHA showed a small increase in the a lattice parameter (9.4418(20) ) and a small decrease in the c lattice parameter (6.8745(17) ), in agreement with the values reported in the literature for precipitated CDHAs. A prolonged milling resulted in an increase of the crystallinity of the CDHA and its partial decomposition into β-TCP by the loss of OH - and HPO 4 2- groups. © 2011 Elsevier B.V. All rights reserved.

Acu K.,Universitaetsmedizin Berlin | Scheel M.,Universitaetsmedizin Berlin | Issever A.S.,Universitaetsmedizin Berlin
Osteoporosis International | Year: 2014

Summary: Our study has demonstrated that in contrastenhanced multi-detector computed tomography (MDCT)- based bone density measurements, the scan delay time after contrast agent administration is a statistically significant variable for the derivation of quantitative computed tomography (QCT)-equivalent bone mineral density (BMD) values. Introduction: Earlier investigators have proposed to derive QCT-equivalent BMD values from contrast-enhanced MDCT scans by using a merely density-based conversion equation. The purpose of this study was to investigate whether the scan delay after intravenous (IV) contrast agent administration might affect BMD values derived in this way. Methods: A retrospective data analysis was performed on 198 subjects who underwent standardized biphasic MDCT. Average densities values (in Hounsfield units) of lumbar vertebral bodies 1 to 3 (L1-L3) were compared between phases I and II of the biphasic MDCT scan. Furthermore, QCT-equivalent BMD (BMDQCT) values were calculated using a previously published conversion equation. Results: Paired t-test analysis revealed that IV contrast agent administration leads to a statistically significant increase (8.6%; p <0.0001) in overall density of L1-L3 from phases I to II. Moreover, comparison of BMDQCT values between phases I and II reveals a change from osteoporotic to osteopenic in 4.5% of the study population and from osteopenic to normal for 11.1% of the subjects. Furthermore, it was revealed that the density increase from phases I to II shows a weak, yet statistically significant (p <0.001) age dependency. Conclusions: Our study demonstrates that the use of a mere density-based conversion equation for deriving BMDQCT from MDCT scans ignores time dependency as an important variable. Furthermore, our results indicate that the actual age-dependent BMD itself might be another relevant variable that needs to be included in a MDCT-to-QCT conversion equation. © International Osteoporosis Foundation and National Osteoporosis Foundation 2013.

Nickles H.T.,Universitaetsmedizin Berlin | Sumkauskaite M.,German Cancer Research Center | Wang X.,German Cancer Research Center | Wegner I.,German Cancer Research Center | And 4 more authors.
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2014

The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies. © 2014 the American Physiological Society.

Menenakos C.,Universitaetsmedizin Berlin | Kilian M.,Universitaetsmedizin Berlin | Hartmann J.,Universitaetsmedizin Berlin
Hernia | Year: 2010

Purpose To report the initial clinical case of single-port transabdominal preperitoneal (TAPP) bilateral inguinal hernia repair. Methods One patient with symptomatic bilateral inguinal hernias underwent a single-port TAPP hernia repair using the Triport Single Port System (ASC, TriPort Laparoscopic Access Device, Wicklow, Ireland). The device was placed through a single supraumbilical incision. Hernia repair was performed with a typical TAPP technique with implantation of an Ultrapro® Mesh (Ethicon, Norderstedt, Germany). Results The procedure was technically successful without placement of additional trocars. Operative time was 120 min. No blood loss and no intraoperative complications were observed. The patient was discharged on the 2nd postoperative day and follow-up at 2 weeks demonstrated the patient to be without complaints with uncomplicated wound healing. Conclusion Single-port TAPP bilateral inguinal hernia repair is technically feasible and safe. © Springer-Verlag 2009.

Wiedemann A.U.,Free University of Berlin | Gardner B.,University College London | Knoll N.,Free University of Berlin | Burkert S.,Universitaetsmedizin Berlin
Applied Psychology: Health and Well-Being | Year: 2014

Background: Habit formation is thought to lead to long-term maintenance of fruit and vegetable consumption. Habits develop through context-dependent repetition, but additional variables such as intrinsic reward of behaviour may influence habit strength. Drawing upon the Associative-Cybernetic Model, this exploratory study tested different pathways by which intrinsic reward may influence fruit and vegetable consumption habit strength. Methods: In a three-wave study of fruit and vegetable intake in adults (N=127) from the general population, intrinsic reward, intention, and self-efficacy were assessed at baseline, fruit and vegetable consumption and intrinsic reward two weeks later, and habit strength another two weeks later. Direct, indirect, and moderation effects of intrinsic reward on habit strength were tested simultaneously in a moderated mediation model. Results: Intrinsic reward had a positive indirect effect on habit strength through its influence on the frequency of fruit and vegetable consumption. Further, the relationship between fruit and vegetable consumption and habit was stronger where consumption was considered more intrinsically rewarding. Conclusions: Findings highlight the potential relevance of intrinsic reward to habit. We suggest that intrinsic rewards from behaviour may not only facilitate habit via behaviour frequency, but also reinforce the relationship between behavioural repetition and habit strength. © 2013 The International Association of Applied Psychology.

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